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 #learning #memo Do not learn if you do not understand

20 rules of formulating knowledge in learning
will proceed with learning using spaced repetition, i.e. you will not just learn once but you will repeat the material optimally (as in SuperMemo). The 20 rules of formulating knowledge in learning <span>Do not learn if you do not understand Trying to learn things you do not understand may seem like an utmost waste of time. Still, an amazing proportion of students commit the offence of learning without comprehension. Very of

#learning #memo

#### Learn before you memorize

Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge. Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension mentioned in Rule 1: Do not learn if you do not understand. A single separated piece of your big picture is like a single German word in the textbook of history.

Do not start from memorizing loosely related facts! First read a chapter in your book that puts them together (e.g. the principles of the internal combustion engine). Only then proceed with learning using individual questions and answers (e.g. What moves the pistons in the internal combustion engine?), etc.

20 rules of formulating knowledge in learning
and you may tend to blame yourself for lack of comprehension. Soon you may pollute your learning process with a great deal of useless material that treacherously makes you believe "it will be useful some day". <span>Learn before you memorize Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge . Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension mentioned in Rule 1: Do not learn if you do not understand. A single separated piece of your big picture is like a single German word in the textbook of history. Do not start from memorizing loosely related facts! First read a chapter in your book that puts them together (e.g. the principles of the internal combustion engine). Only then proceed with learning using individual questions and answers (e.g. What moves the pistons in the internal combustion engine?), etc. Build upon the basics The picture of the learned whole (as discussed in Rule 2: Learn before you memorize) does not have to be complete to the last detail. Just the opposite,

#### Annotation 150913092

 #learning #memo Graphic deletion is as good as cloze deletion

20 rules of formulating knowledge in learning
ome automatic! Exemplary mind map: Six Steps mind map generated in Mind Manager 3.5, imported to SuperMemo 2004, courtesy of John England, TeamLink Australia) <span>Graphic deletion is as good as cloze deletion Graphic deletion works like cloze deletion but instead of a missing phrase it uses a missing image component. For example, when learning anatomy, you might present a complex illustration

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#learning #memo
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Do not learn if you do not [...]
understand

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Do not learn if you do not understand

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20 rules of formulating knowledge in learning
will proceed with learning using spaced repetition, i.e. you will not just learn once but you will repeat the material optimally (as in SuperMemo). The 20 rules of formulating knowledge in learning <span>Do not learn if you do not understand Trying to learn things you do not understand may seem like an utmost waste of time. Still, an amazing proportion of students commit the offence of learning without comprehension. Very of

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#learning #memo
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#### Learn before you

[...]

Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge. Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension mentioned in Rule 1: Do not learn if you do not understand. A single separated piece of your big picture is like a single German word in the textbook of history.

Do not start from memorizing loosely related facts! First read a chapter in your book that puts them together (e.g. the principles of the internal combustion engine). Only then proceed with learning using individual questions and answers (e.g. What moves the pistons in the internal combustion engine?), etc.

memorize

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Learn before you memorize Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge . Only when individual pieces fit to build a single coherent

#### Original toplevel document

20 rules of formulating knowledge in learning
and you may tend to blame yourself for lack of comprehension. Soon you may pollute your learning process with a great deal of useless material that treacherously makes you believe "it will be useful some day". <span>Learn before you memorize Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge . Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension mentioned in Rule 1: Do not learn if you do not understand. A single separated piece of your big picture is like a single German word in the textbook of history. Do not start from memorizing loosely related facts! First read a chapter in your book that puts them together (e.g. the principles of the internal combustion engine). Only then proceed with learning using individual questions and answers (e.g. What moves the pistons in the internal combustion engine?), etc. Build upon the basics The picture of the learned whole (as discussed in Rule 2: Learn before you memorize) does not have to be complete to the last detail. Just the opposite,

#### Flashcard 1429259291916

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#cfa #cfa-level-1 #economics #microeconomics #reading-13-demand-and-supply-analysis-introduction #study-session-4
Question
Consumer Surplus Intuitive Example?
Last thing you purchased.

How much you actually paid for it

Contrast that price with the maximum amount you would have been willing to pay for it.

If you were willing to pay more you received a surplus (bargain)

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To get an intuitive feel for this concept, consider the last thing you purchased. Whatever it was, think of how much you actually paid for it. Now contrast that price with the maximum amount you would have been willing to pay for it instead of going without it altogether. If those two numbers are different, we say you received some consumer surplus from your purchase. You received a “bargain” because you were willing to pay more than you had to pay.

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3.9. Consumer Surplus—Value minus Expenditure
cepts called consumer surplus and producer surplus to address that question. We will begin with consumer surplus, which is a measure of how much net benefit buyers enjoy from the ability to participate in a particular market. <span>To get an intuitive feel for this concept, consider the last thing you purchased. Maybe it was a cup of coffee, a new pair of shoes, or a new car. Whatever it was, think of how much you actually paid for it. Now contrast that price with the maximum amount you would have been willing to pay for it instead of going without it altogether. If those two numbers are different, we say you received some consumer surplus from your purchase. You received a “bargain” because you were willing to pay more than you had to pay. Earlier we referred to the law of demand, which says that as price falls, consumers are willing to buy more of the good. This observation translates into a negatively slope

#### Flashcard 1433027611916

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#algebra-baldor
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Cuando una letra no tiene exponente, su exponente es [...]

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Cuando una letra no tiene exponente, su exponente es la unidad.

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Capital budgeting is the process of [...] on [...] whose cash flows are expected to extend beyond one year.
planning expenditures

assets (fixed assets)

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Capital budgeting is the process of planning expenditures on assets (fixed assets) whose cash flows are expected to extend beyond one year. Managers analyze projects and decide which ones to include in the capital budget. <

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Subject 1. Capital Budgeting: Introduction
Capital budgeting is the process of planning expenditures on assets (fixed assets) whose cash flows are expected to extend beyond one year. Managers analyze projects and decide which ones to include in the capital budget. "Capital" refers to long-term assets. The "budget" is a plan which details projected cash inflows and outflows during a future period. &#1

#### Flashcard 1441844563212

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Capital budgeting decisions are based on [...]
incremental after-tax cash flows discounted at the opportunity cost of capital.

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Capital budgeting decisions are based on incremental after-tax cash flows discounted at the opportunity cost of capital.

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Subject 2. Basic Principles of Capital Budgeting
Capital budgeting decisions are based on incremental after-tax cash flows discounted at the opportunity cost of capital. Assumptions of capital budgeting are: Capital budgeting decisions must be based on cash flows, not accounting income. Accounting profits only measure the return on t

#### Flashcard 1464672324876

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#48-laws-of-power #keys-to-power #law-2-never-trust-friends-learn-how-to-use-enemies
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Mao’s strategy of constant conflict has several key components:

First, be [...]

certain that eventually you will win.

Never pick a fight with someone you are not sure you can defeat, as Mao knew the Japanese would be defeated in time.

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Mao’s strategy of constant conflict has several key components: First, be certain that in the long run you will emerge victorious. Never pick a fight with someone you are not sure you can defeat, as Mao knew the Japanese would be defeated in time. Second, if you have no apparent enemies, you must sometim

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#### Flashcard 1473889832204

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The [...] method of reporting cash flows from operating activities discloses major classes of gross cash receipts and gross cash payments.
direct method

Examples are cash received from customers and cash paid to suppliers and employees.

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The direct method of reporting cash flows from operating activities discloses major classes of gross cash receipts and gross cash payments. Examples of such classes are cash received from customers and c

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3.1.4. Cash Flow Statement
rrals, and transactions of an investing and financing nature to arrive at the amount of cash generated from operating activities of €12,741 million. This approach to reporting cash flow from operating activities is termed the indirect method. <span>The direct method of reporting cash flows from operating activities discloses major classes of gross cash receipts and gross cash payments. Examples of such classes are cash received from customers and cash paid to suppliers and employees. The indirect method emphasizes the different perspectives of the income statement and cash flow statement. On the income statement, income is reported when earned, not nece

#### Flashcard 1478460312844

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Grouping expenses into Cost of Goods Sold is an example of grouping by [...].

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An example of grouping by function would be grouping together expenses into a category such as cost of goods sold, which may include labour and material costs, depreciation, some salaries (e.g., salespeople’s), and other

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2. COMPONENTS AND FORMAT OF THE INCOME STATEMENT
nature or function. Grouping together expenses such as depreciation on manufacturing equipment and depreciation on administrative facilities into a single line item called “depreciation” is an example of a grouping by nature of the expense. <span>An example of grouping by function would be grouping together expenses into a category such as cost of goods sold, which may include labour and material costs, depreciation, some salaries (e.g., salespeople’s), and other direct sales related expenses.8 Both Danone and Kraft present their expenses by function, which is sometimes referred to “cost of sales” method. One subtotal often shown in an income statement is gross

#### Flashcard 1479061671180

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#daniel-goleman #emotional-brain #emotional-iq #what-are-emotions-for #when-passions-overwhelm-reasons
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Despite social constraints, [...] time and again.
passions overwhelm reason

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Despite social constraints, passions overwhelm reason time and again.

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 #incremental-reading Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge.

20 rules of formulating knowledge in learning
me yourself for lack of comprehension. Soon you may pollute your learning process with a great deal of useless material that treacherously makes you believe "it will be useful some day". Learn before you memorize <span>Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge . Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension m

#### Annotation 1767079546124

 #incremental-reading Basics are usually easy to retain and only take a tiny proportion of your time.

20 rules of formulating knowledge in learning
bvious things is not a waste of time! Basics may also appear volatile and the cost of memorizing easy things is little. Better err on the safe side. Remember that usually you spend 50% of your time repeating just 3-5% of the learned material! <span>Basics are usually easy to retain and take a tiny proportion of your time. However, each memory lapse on a basic fact can be very costly! Stick to the minimum information principle The material you learn must be formulated in as simple way

#### Annotation 1767081118988

 #incremental-reading simplicity makes is easy for the brain to always process it the same way.

20 rules of formulating knowledge in learning
plicity is imperative due to the way the brain works. There are two main reasons for which knowledge must be simple: Simple is easy By definition, simple material is easy to remember. This comes from the fact that its <span>simplicity makes is easy for the brain to process in always it the same way. Imagine a labyrinth. When making a repetition of a piece of material, your brain is running through a labyrinth (you can view a neural network as a tangle of paths). While running throu

#### Annotation 1767082691852

 #incremental-reading splitting complex items into sub-items saves time because each item can be repeated at its own pace

20 rules of formulating knowledge in learning
the learned material using optimum inter-repetition intervals (as in SuperMemo). If you consider an item that is composed of two sub-items, you will need to make repetitions that are frequent enough to keep the more difficult item in memory. <span>If you split the complex item into sub-items, each can be repeated at its own pace saving your time. Very often, inexperienced students create items that could easily be split into ten or more simpler sub-items! Although the number of items increases, the number of repetitions of eac

#### Annotation 1767084264716

20 rules of formulating knowledge in learning
u benefit from simplifying your items ! Note in the example above how short the questions are. Note also that the answers are even shorter! We want a minimum amount of information to be retrieved from memory in a single repetition! <span>We want answer to be as short as imaginably possible ! You will notice that the knowledge learned in the ill-structured example is not entirely equivalent to the well-structured formulation. For example, although you will remember

#### Annotation 1767085837580

 #incremental-reading the longer the time you need to remember knowledge, the more you benefit from simplifying your items!

20 rules of formulating knowledge in learning
You might want to experiment and try to learn two subjects using the two above approaches and see for yourself what advantage is brought by minimum information principle. This is particularly visible in the long perspective, i.e. <span>the longer the time you need to remember knowledge, the more you benefit from simplifying your items ! Note in the example above how short the questions are. Note also that the answers are even shorter! We want a minimum amount of information to be retrieved from memory in a si

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20 rules of formulating knowledge in learning

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Cloze deletion makes the core of [...]

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Cloze deletion makes the core of incremental reading.

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20 rules of formulating knowledge in learning
tion principle, use cloze deletion! If you are an advanced user, you will also like cloze deletion. It is a quick and effective method of converting textbook knowledge into knowledge that can be subject to learning based on spaced repetition. <span>Cloze deletion makes the core of the fast reading and learning technique called incremental reading. Ill-formulated knowledge - Complex and wordy Q: What was the history of the Kaleida company? A: Kaleida, funded to the tune of \$40 million by Apple C

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In mind maps, connections between items reflect [...].
logical connections between concepts

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In mind maps, connections between items reflect logical connections between concepts.

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20 rules of formulating knowledge in learning
erial. Well-employed images will greatly reduce your learning time in areas such as anatomy, geography, geometry, chemistry, history, and many more. The power of imagery explains why the concept of Tony Buzan's mind maps is so popular. <span>A mind map is an abstract picture in which connections between its components reflect the logical connections between individual concepts. Less beneficial formulation Q: What African country is located between Kenya, Zambia and Mozambique? A: Tanzania More

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[...] explains why the concept of mind maps is so popular.
The power of imagery

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The power of imagery explains why the concept of mind maps is so popular.

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20 rules of formulating knowledge in learning
robably always have to weigh up cost and profits in using graphics in your learning material. Well-employed images will greatly reduce your learning time in areas such as anatomy, geography, geometry, chemistry, history, and many more. <span>The power of imagery explains why the concept of Tony Buzan's mind maps is so popular. A mind map is an abstract picture in which connections between its components reflect the logical connections between individual concepts. Less beneficial formulation

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[...] are various techniques that make remembering easier.
Mnemonic techniques

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Mnemonic techniques are various techniques that make remembering easier.

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20 rules of formulating knowledge in learning
A: Tanzania More effective formulation Q: What African country is marked white on the map? A: Tanzania Use mnemonic techniques <span>Mnemonic techniques are various techniques that make remembering easier. They are often amazingly effective. For most students, a picture of a 10-year-old memorizing a sequence of 50 playing cards verges on discovering a young genius. It is very surprising t

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the true bottleneck towards [...] is not in quick memorization, but in long-term retention.
long-lasting and useful memories

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the true bottleneck towards long-lasting and useful memories is not in quick memorization, but in long-term retention.

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20 rules of formulating knowledge in learning
raining. These techniques are available to everyone and do not require any special skills! Before you start believing that mastering such techniques will provide you with an eternal solution to the problem of forgetting, be warned that <span>the true bottleneck towards long-lasting and useful memories is not in quickly memorizing knowledge! This is indeed the easier part. The bottleneck lies in retaining memories for months, years or for lifetime! To accomplish the latter you will need SuperMemo and the compliance with the 20 rules presented herein. There have been dozens of books written about mnemonic techniques. Probabl

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the true bottleneck towards long-lasting and useful memories is not in [...], but in long-term retention.
quick memorization

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the true bottleneck towards long-lasting and useful memories is not in quick memorization, but in long-term retention.

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20 rules of formulating knowledge in learning
raining. These techniques are available to everyone and do not require any special skills! Before you start believing that mastering such techniques will provide you with an eternal solution to the problem of forgetting, be warned that <span>the true bottleneck towards long-lasting and useful memories is not in quickly memorizing knowledge! This is indeed the easier part. The bottleneck lies in retaining memories for months, years or for lifetime! To accomplish the latter you will need SuperMemo and the compliance with the 20 rules presented herein. There have been dozens of books written about mnemonic techniques. Probabl

#### Flashcard 1767170247948

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the true bottleneck towards long-lasting and useful memories is not in quick memorization, but in [...].
long-term retention

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the true bottleneck towards long-lasting and useful memories is not in quick memorization, but in long-term retention.

#### Original toplevel document

20 rules of formulating knowledge in learning
raining. These techniques are available to everyone and do not require any special skills! Before you start believing that mastering such techniques will provide you with an eternal solution to the problem of forgetting, be warned that <span>the true bottleneck towards long-lasting and useful memories is not in quickly memorizing knowledge! This is indeed the easier part. The bottleneck lies in retaining memories for months, years or for lifetime! To accomplish the latter you will need SuperMemo and the compliance with the 20 rules presented herein. There have been dozens of books written about mnemonic techniques. Probabl

#### Flashcard 1767171820812

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[...] works great in learning geography!
Graphic deletion

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Graphic deletion works great in learning geography!

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20 rules of formulating knowledge in learning
present a complex illustration. Only a small part of it would be missing. The student's job is to name the missing area. The same illustration can be used to formulate 10-20 items! Each item can ask about a specific subcomponent of the image. <span>Graphic deletion works great in learning geography! Exemplary graphic deletion: SuperMemo 2000/2002 SuperMemo 99 This is how you can quickly generate graphic deletion using a picture from the

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[...] should always be avoid due to the high cost of retaining such items.
Sets

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Sets should always be avoid due to the high cost of retaining such items.

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20 rules of formulating knowledge in learning
. For example, a set of fruits might be an apple, a pear and a peach. A classic example of an item that is difficult to learn is an item that asks for the list of the members of a set. For example: What countries belong to the European Union? <span>You should avoid such items whenever possible due to the high cost of retaining memories based on sets. If sets are absolutely necessary, you should always try to convert them into enumerations. Enumerations are ordered lists of members (for example, the alphabetical list of the members o

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enumerations are ordered and thus force the brain to [...].
always list them in the same order

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enumerations are ordered and thus force the brain to always list them in the same order.

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20 rules of formulating knowledge in learning
ecessary, you should always try to convert them into enumerations. Enumerations are ordered lists of members (for example, the alphabetical list of the members of the EU). Enumerations are also hard to remember and should be avoided. However, <span>the great advantage of enumerations over sets is that they are ordered and they force the brain to list them always in the same order. An ordered list of countries contains more information than the set of countries that can be listed in any order. Paradoxically, despite containing more information, enumerations are ea

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you should always try to make sure your brain [...] at each repetition.
works in the exactly same way

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you should always try to make sure your brain works in the exactly same way at each repetition .

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20 rules of formulating knowledge in learning
he set of countries that can be listed in any order. Paradoxically, despite containing more information, enumerations are easier to remember. The reason for this has been discussed earlier in the context of the minimum information principle: <span>you should always try to make sure your brain works in the exactly same way at each repetition . In the case of sets, listing members in varying order at each repetition has a disastrous effect on memory. It is nearly impossible to memorize sets containing more than five members wi

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Learning poems is an example of learning [...]
enumerations

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Learning poems is an example of learning enumerations

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20 rules of formulating knowledge in learning
ra information is added in extra items . You can also deal with enumerations by using grouping like in the case of sets (see the European Union example) but cloze deletions should be simpler and should suffice in most cases. <span>Learning poems is an example of learning enumerations (all words and sentences have to be uttered in a predefined sequence); however, due to strong semantic connections, the rhyme and the rhythm, it may often be possible to effectively rem

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If knowledge of one item makes it harder to remember another item, we have a case of [...].
memory interference

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If knowledge of one item makes it harder to remember another item, we have a case of memory interference .

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20 rules of formulating knowledge in learning
often confuse them. For example, you may have problems distinguishing between the meanings of the words historic and historical. This will even be more visible if you memorize lots of numbers, e.g. optimum dosages of drugs in pharmacotherapy. <span>If knowledge of one item makes it harder to remember another item, we have a case of memory interference . You can often remember an item for years with straight excellent grades until ... you memorize another item that makes it nearly impossible to remember either! For example, if you learn

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[...] is probably the single greatest cause of forgetting
Interference

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Interference is probably the single greatest cause of forgetting

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20 rules of formulating knowledge in learning
the location of all these countries, and French Guyana, and Colombia and more, you will suddenly notice strong memory interference and you may experience unexpected forgetting. In simple terms: you will get confused about what is what. <span>Interference is probably the single greatest cause of forgetting in collections of an experienced user of SuperMemo. You can never be sure when it strikes, and the only hermetic procedure against it is to detect and eliminate . In other words, in ma

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Interference is probably the single greatest cause of [...]
forgetting

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Interference is probably the single greatest cause of forgetting

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20 rules of formulating knowledge in learning
the location of all these countries, and French Guyana, and Colombia and more, you will suddenly notice strong memory interference and you may experience unexpected forgetting. In simple terms: you will get confused about what is what. <span>Interference is probably the single greatest cause of forgetting in collections of an experienced user of SuperMemo. You can never be sure when it strikes, and the only hermetic procedure against it is to detect and eliminate . In other words, in ma

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the only hermetic procedure against interference is to [...].
detect and eliminate

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the only hermetic procedure against interference is to detect and eliminate .

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20 rules of formulating knowledge in learning
cted forgetting. In simple terms: you will get confused about what is what. Interference is probably the single greatest cause of forgetting in collections of an experienced user of SuperMemo. You can never be sure when it strikes, and <span>the only hermetic procedure against it is to detect and eliminate . In other words, in many cases it may be impossible to predict interference at the moment of formulating knowledge. Interference can also occur between remotely related items like Guyana

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[...] must be optimized to make sure that the brain can recall it with minimum effort.
wording

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wording must be optimized to make sure that the brain can recall it with minimum effort.

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20 rules of formulating knowledge in learning
apt but I will never know which is which!") in SuperMemo use View : Other browsers : Leeches (Shift+F3) to regularly review and eliminate most difficult items read more: Memory interference Optimize wording <span>The wording of your items must be optimized to make sure that in minimum time the right bulb in your brain lights up. This will reduce error rates, increase specificity, reduce response time, and help your concentration. Less optimum item: cloze deletion that is too wordy Q:

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wording must be optimized to ensure [...].
minimum-effort recall

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wording must be optimized to make sure that the brain can recall it with minimum effort.

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20 rules of formulating knowledge in learning
apt but I will never know which is which!") in SuperMemo use View : Other browsers : Leeches (Shift+F3) to regularly review and eliminate most difficult items read more: Memory interference Optimize wording <span>The wording of your items must be optimized to make sure that in minimum time the right bulb in your brain lights up. This will reduce error rates, increase specificity, reduce response time, and help your concentration. Less optimum item: cloze deletion that is too wordy Q:

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[...] is not supposed to be memorised as a side effect.
trailing information

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trailing information is not supposed to be memorised as a side effect.

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20 rules of formulating knowledge in learning
etter: Q: PageMaker lost ground to ... A: Quark Note that the loss of information content in this item is inconsequential. During repetition you are only supposed to learn the name: Quark. <span>You should not hope that the trailing messages on the ownership of PageMaker and the year of its development will somehow trickle to your memory as a side effect. You should decide if the other pieces of information are important to you and if so, store them in separate items (perhaps reusing the above text, employing cloze deletion again and opt

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[...] can place your item in a better context, simplify wording, and reduce interference.
Cross-reference to other items

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Cross-reference to other items can place your item in a better context, simplify wording, and reduce interference.

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20 rules of formulating knowledge in learning
eparate items (perhaps reusing the above text, employing cloze deletion again and optimizing the wording in a new way). Otherwise the redundant information will only slow down your learning process! Refer to other memories <span>Referring to other memories can place your item in a better context, simplify wording, and reduce interference. In the example below, using the words humble and supplicant helps the student focus on the word shamelessly and thus strengthen the correct semantics. Better focus helps eliminating int

#### Flashcard 1767199345932

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One of the most effective ways of enhancing recollection is to provide it with [...].

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One of the most effective ways of enhancing recollection is to provide them with personal links.

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20 rules of formulating knowledge in learning
Item that uses interfering memories to amplify the correct meaning Q: derog: adj: shamelessly humble and supplicant A: cringing Personalize and provide examples <span>One of the most effective ways of enhancing memories is to provide them with a link to your personal life. In the example below you will save time if you use a personal reference rather than trying to paint a picture that would aptly illustrate the question Harder item

#### Annotation 1767201705228

 #incremental-reading It is well known that emotional states can facilitate recall

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Use objects that evoke very specific and strong emotions: love, sex, war, your late relative, object of your infatuation, Linda Tripp, Nelson Mandela, etc. It is well known that emotional states can facilitate recall

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20 rules of formulating knowledge in learning
are likely to enhance retrieval (as long as you do not overuse same tools and fall victim of interference!). Your items may assume bizarre form; however, as long as they are produced for your private consumption, the end justifies the means. <span>Use objects that evoke very specific and strong emotions: love, sex, war, your late relative, object of your infatuation, Linda Tripp, Nelson Mandela, etc. It is well known that emotional states can facilitate recall; however, you should make sure that you are not deprived of the said emotional clues at the moment when you need to retrieve a given memory in a real-life situation Harder item

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It is well known that [...love, sex...] can facilitate recall
emotional states

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It is well known that emotional states can facilitate recall

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20 rules of formulating knowledge in learning
are likely to enhance retrieval (as long as you do not overuse same tools and fall victim of interference!). Your items may assume bizarre form; however, as long as they are produced for your private consumption, the end justifies the means. <span>Use objects that evoke very specific and strong emotions: love, sex, war, your late relative, object of your infatuation, Linda Tripp, Nelson Mandela, etc. It is well known that emotional states can facilitate recall; however, you should make sure that you are not deprived of the said emotional clues at the moment when you need to retrieve a given memory in a real-life situation Harder item

#### Flashcard 1767207210252

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[...] can be used to simplify wording of items
Context cues

The tags in my system

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20 rules of formulating knowledge in learning
This is roughly equivalent to 25-fold saving in time in the period of 20 years ! Such examples are not rare! They are most effectively handled with the all the preceding rules targeted on simplicity and against the interference <span>Context cues simplify wording You can use categories in SuperMemo 2000/2002, provide different branches of knowledge with a different look (different template), use reference labels (Title, Author, Date, etc.

#### Flashcard 1767209569548

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Memorizing [...] is recommended in cases where a given memory is of high value.
different representations of the same fact or rule

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Memorizing different representations of the same fact or rule is recommended in cases where a given memory is of high value.

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20 rules of formulating knowledge in learning
vity and intelligence read: Roots of genius and creativity, as well as more specific: Derivation, reasoning and intelligence multiple semantic representation : very often the same knowledge can be represented and viewed from different angles. <span>Memorizing different representations of the same fact or rule is recommended in cases where a given memory is of high value. This will increase the expected recall rate (beyond that specified with the forgetting index)! flexible repetition : if there are many valid responses to the same question make sure tha

#### Redundancy does not contradict minimum information principle

20 rules of formulating knowledge in learning
stand for in biochemistry? A: glucocorticoid response element Context-labeled items increase success rate Q: bioch: GRE A: glucocorticoid response element <span>Redundancy does not contradict minimum information principle Redundancy in simple terms is more information than needed or duplicate information, etc. Redundancy does not have to contradict the minimum information principle and may even b

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Redundancy

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Redundancy does not contradict minimum information principle

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20 rules of formulating knowledge in learning
stand for in biochemistry? A: glucocorticoid response element Context-labeled items increase success rate Q: bioch: GRE A: glucocorticoid response element <span>Redundancy does not contradict minimum information principle Redundancy in simple terms is more information than needed or duplicate information, etc. Redundancy does not have to contradict the minimum information principle and may even b

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#### Redundancy does not contradict [...] principle

minimum information

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20 rules of formulating knowledge in learning
stand for in biochemistry? A: glucocorticoid response element Context-labeled items increase success rate Q: bioch: GRE A: glucocorticoid response element <span>Redundancy does not contradict minimum information principle Redundancy in simple terms is more information than needed or duplicate information, etc. Redundancy does not have to contradict the minimum information principle and may even b

#### Flashcard 1767217171724

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if there are multiple valid responses to the same question all right answer should be [...].
euqally rewarded

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if there are multiple valid responses to the same question all right answer should be euqally rewarded.

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20 rules of formulating knowledge in learning
Memorizing different representations of the same fact or rule is recommended in cases where a given memory is of high value. This will increase the expected recall rate (beyond that specified with the forgetting index)! flexible repetition : <span>if there are many valid responses to the same question make sure that your representation makes it possible to identify the equivalence and reward you with good grades by providing just one of the equivalent choices. For example, if you learn a language, it rarely make sense to learn all synonyms that meet a definition of a concept. It is more adequate to consider a single synonym as the sufficient

#### Flashcard 1767218744588

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[...] should accompany your items but should not be part of the learned knowledge
Sources

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Sources should accompany your items but should not be part of the learned knowledge

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20 rules of formulating knowledge in learning
one is often long forgotten. With sources provided, you will be able to make more educated choices on which pieces of information are more reliable. Adding reliability labels may also be helpful (e.g. Watch out!, Other sources differ!, etc.). <span>Sources should accompany your items but should not be part of the learned knowledge (unless it is critical for you to be able to recall the source whenever asked). Provide date stamping Knowledge can be relatively stable (basic math, anatomy, taxono

#### Flashcard 1767221103884

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[...] should be included in items to indicate the degree of obsolescence.
time stamps

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time stamps should be included in items to indicate the degree of obsolescence.

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20 rules of formulating knowledge in learning
whenever asked). Provide date stamping Knowledge can be relatively stable (basic math, anatomy, taxonomy, physical geography, etc.) and highly volatile (economic indicators, high-tech knowledge, personal statistics, etc.). <span>It is important that you provide your items with time stamping or other tags indicating the degree of obsolescence. In case of statistical figures, you might stamp them with the year they have been collected. When learning software applications, it is enough you stamp the item with the software versi

#### Flashcard 1767222676748

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time stamps should be included in items to indicate [...].
the degree of obsolescence

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time stamps should be included in items to indicate the degree of obsolescence.

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20 rules of formulating knowledge in learning
whenever asked). Provide date stamping Knowledge can be relatively stable (basic math, anatomy, taxonomy, physical geography, etc.) and highly volatile (economic indicators, high-tech knowledge, personal statistics, etc.). <span>It is important that you provide your items with time stamping or other tags indicating the degree of obsolescence. In case of statistical figures, you might stamp them with the year they have been collected. When learning software applications, it is enough you stamp the item with the software versi

#### Annotation 1767224249612

 #incremental-reading prioritisation is critical for building quality knowledge in the long-term.

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You will always face far more knowledge that you will be able to master. That is why prioritizing is critical for building quality knowledge in the long-term.

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20 rules of formulating knowledge in learning
ill rarely want to memorize stamping itself. If you would like to remember the changes of a given figure in time (e.g. GNP figures over a number of years), the date stamping becomes the learned knowledge itself. Prioritize <span>You will always face far more knowledge that you will be able to master. That is why prioritizing is critical for building quality knowledge in the long-term. The way you prioritize will affect the way your knowledge slots in. This will also affect the speed of learning (e.g. see: learn basics first). There are many stages at which prioritizi

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With information overflow, [...] is critical for building quality knowledge in the long-term.
prioritisation

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prioritisation is critical for building quality knowledge in the long-term.

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20 rules of formulating knowledge in learning
ill rarely want to memorize stamping itself. If you would like to remember the changes of a given figure in time (e.g. GNP figures over a number of years), the date stamping becomes the learned knowledge itself. Prioritize <span>You will always face far more knowledge that you will be able to master. That is why prioritizing is critical for building quality knowledge in the long-term. The way you prioritize will affect the way your knowledge slots in. This will also affect the speed of learning (e.g. see: learn basics first). There are many stages at which prioritizi

#### Flashcard 1767229754636

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make sure that [...] is placed separately so that your attention is focused on the most important part.
explanatory or optional components of the answer

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make sure that explanatory or optional components of the answer are placed separately so that your attention is focused on the most important part.

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20 rules of formulating knowledge in learning
he item or items. If formulation requires more knowledge, more time, comparing with other sources, etc. you can just import. Otherwise, if you believe that formulating an accurate item is a matter of seconds, formulate it Formulating items - <span>make sure that explanatory or optional components of the answer are placed in the parentheses so that your attention is focused on the most important part of the item. The parts in the parentheses can be read after the repetition to strengthen the memory in its context Using forgetting index - you can use the forgetting index to prioritize pending it

#### Annotation 1767234211084

 #has-images 一年返现40%，被吓到的我 梁萧 发布于 7小时前分类：文摘 一位读者留言： XX银行推销我一个理财产品，看起来特别诱人。 年存2万，每年返4000元一辈子 年存5万，每年返10000元一辈子 ...... 年存100万，每年返20万一辈子 只需存五年，就返一辈子 年金可取走，不取自动进入分红账户，3.5%年复利滚存，还有分红拿。 小伙伴一下被吸引了： ——我一年存5万，存五年就行，每年返一万元，返一辈子。 这么好的事，小姐姐，你怎么看？ 我怎么看，点一首《套路》送他们。 一. 上面这个例子，特别常见——每年存N万，年年能领钱、一直领到死。 很多人都遇到过。 银行的人会说，你可以拿这钱去当教育金、养老金、婚嫁金，留给孩子，那也是一大笔财富啊。 是不是有买买买的冲动，以为自己摇身一变千万富翁？ 其实没那么神奇，它就是一款年金险。0保障功能，纯投资用的，年年返现，有的还带分红。 它的收益其实不高，为什么交几年，就能返现一辈子呢？ 因为复利的魔力啊。 二. 之前我跟大家说过七十二法则—— 用72除以本金翻倍的时间，可以估算理财的年化收益。 假如20岁开始买这个产品，每年交2万，共交五年，也就是总共交10万元。 然后一年返4000元，那就是要返25年，才能回本。 它的收益率大概是多少呢？72/25=2.88%。 妈诶，还不如买余额宝呢。 这是钱每年都取出来的情况下，如果一直只存不取呢？ 这个产品附加了分红功能，钱一直不取，年化收益是3.5%。 72/3.5=20年。 也就是说，一分不取的情况下，一共要存20年的时间，才能赚回本钱。 用IRR公式计算，结果也差不多。 这么一看，是不是吸引力一下子就大打折扣了？ 三. 大家留心的话，这几年银行电话销售的产品，许多都是“一年交N万，年年返现、返一辈子”的年金险。 有的设计的特别花哨，什么生存金啦、养老金啦、身故金啦、这个账户、那个分红的。 眼花缭乱。 但无论多么复杂，用IRR公式一算便知，收益大多只有3-4%，而且还是存几十年的情况下。 5%以上的极罕见。 这类产品，不可能像话术忽悠的那样，收益特高，能当婚嫁金、教育金、养老金用。 你要真报着这样的目的买，钱早就被通胀吞噬了... 我对年金险没意见，它有存在的价值，主要是它的营销话术特别泛滥，适合扒一扒。 四. 还有一点，银行在推这种产品时，绝对不会提到中途退保风险的。 甚至可能连这是保险，都不会说。 保险是没有保本概念的。想拿回本金，要么是持有达到一定期限、要么是达到赔付标准。 提前退保的话，损失超大的。 年金险也一样。 不是我黑银行啊...只是有时候在营销上，真的挺不靠谱。 我之前也接过类似电话，小伙子上来一通吹——我们这产品限量版，特别好，折算下来，一年给你40%... 我天，庞氏都不敢这么吹吧？ 一追问才知道，一年存一万，返现4000，可不就是40%嘛...谁也没说是收益40%啊。 你自己误以为的，怪我咯？ 这就是典型的营销话术了，模糊信息、似是而非，让你自己进圈套。 聊理财，就突出利润，回避风险； 聊保险，就突出回报，回避期限； 聊贷款，就突出金额，回避成本； 死缠烂打跟你磨一个小时，一点儿错都挑不出来，脑子稍一晕，就被带坑里了。 就欺负你不懂，怎么破？

#### Annotation 1767255969036

 #Biochemistry the rate of a pathway may be influenced by the availability of substrates, product inhibi- tion, or alterations in the levels of allosteric activators or inhibitors. These intracellular signals typically elicit rapid responses, and are important for the moment-to-moment regulation of metabolism.

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#### Annotation 1767259114764

 #Biochemistry Signaling between cells provides for long-range integration of metabolism, and usually results in a response that is slower than is seen with signals that originate within the cell. Communication between cells can be mediated, for example, by surface-to-surface contact and, in some tissues, by for- mation of gap junctions, allowing direct communication between the cytoplasms of adjacent cells. However, for energy metabolism, the most important route of communication is chemical signaling between cells by bloodborne hormones or by neurotransmitters.

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#### Annotation 1767261474060

 #Biochemistry tissues that respond to more than one chemical signal must have several different receptors, each of which can be linked to adenylyl cyclase . These receptors, known as G protein-coupled receptors (GPCR), are characterized by an extracellular ligand-bind- ing region, seven transmembrane helices, and an intracellular domain that interacts with G proteins

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#### Annotation 1767263833356

 #Biochemistry The effect of the activated, occupied GPCR on second messenger formation is not direct but, rather, is mediated by specialized trimeric proteins (α, β, γ sub- units) of the cell membrane. These proteins, referred to as G pro- teins because they bind guanosine nucleotides (GTP and GDP), form a link in the chain of communication between the receptor and adenylyl cyclase .

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#### Annotation 1767266192652

 #Biochemistry Many molecules of active Gα protein are formed by one activated receptor. [Note: The ability of a hor- mone or neurotransmitter to stimulate or inhibit adenylyl cyclase depends on the type of Gα protein that is linked to the receptor. One family of G proteins, designated G s , stimulates adenylyl cyclase ; another family, designated G i , inhibits the enzyme

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#### Annotation 1767268551948

 #Biochemistry The next key link in the cAMP second messen- ger system is the activation by cAMP of a family of enzymes called cAMP-independent protein kinases , for example, protein kinase A (Figure 8.8). Cyclic AMP activates protein kinase A by binding to its two regulatory subunits, causing the release of active catalytic subunits. The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. The phosphorylated proteins may act directly on the cell’s ion channels, or, if enzymes, may become activated or inhibited. Protein kinase A can also phosphorylate proteins that bind to DNA, causing changes in gene expression. [Note: Several types of protein kinases are not cAMP-dependent, for example, protein kinase C

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#### Annotation 1767270911244

 #Biochemistry The phosphate groups added to proteins by protein kinases are removed by protein phosphatases —enzymes that hydrolytically cleave phosphate esters (see Figure 8.8). This ensures that changes in protein activity induced by phosphorylation are not permanent

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#### Annotation 1767273270540

 #Biochemistry cAMP is rapidly hydrolyzed to 5'-AMP by cAMP phospho diesterase , one of a family of enzymes that cleave the cyclic 3',5'-phosphodiester bond.

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#### Annotation 1767275629836

 #Biochemistry cAMP is rapidly hydrolyzed to 5'-AMP by cAMP phospho diesterase , one of a family of enzymes that cleave the cyclic 3',5'-phosphodiester bond. 5'-AMP is not an intracellular signaling molecule. Thus, the effects of neurotransmitter- or hormone-mediated

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#### Annotation 1767277989132

 #Biochemistry increases of cAMP are rapidly terminated if the extracellular signal is removed. [Note: Phosphodiesterase is inhibited by methyl xanthine derivatives, such as theophylline and caffeine. 1

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#### Annotation 1767280348428

 #Biochemistry Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen. This series of ten reactions is called aerobic glycolysis because oxygen is required to reoxidize the NADH formed during the oxidation of glyceraldehyde 3-phosphate (Figure 8.9B). Aerobic glycolysis sets the stage for the oxidative decarboxylation of pyruvate to acetyl CoA, a major fuel of the TCA (or citric acid) cycle. Alternatively, pyruvate is reduced to lactate as NADH is oxidized to NAD + (Figure 8.9C). This conversion of glucose to lactate is called anaerobic glycolysis because it can occur without the participation of oxygen. Anaerobic glycolysis allows the production of ATP in tissues that lack mitochondria (for example, red blood cells) or in cells deprived of sufficient oxygen

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#### Annotation 1767282969868

 #Biochemistry Glucose cannot diffuse directly into cells, but enters by one of two trans- port mechanisms: a Na + -independent, facilitated diffusion transport sys- tem or a Na + -monosaccharide cotransporter system.

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#### Annotation 1767285329164

 #Biochemistry The glucose trans- porters display a tissue-specific pattern of expression. For exam- ple, GLUT-3 is the primary glucose transporter in neurons. GLUT-1 is abundant in erythrocytes and blood brain barrier, but is low in adult muscle, whereas GLUT-4 is abundant in adipose tis- sue and skeletal muscle. [Note: The number of GLUT-4 trans- porters active in these tissues is increased by insulin.

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#### Annotation 1767287688460

 #Biochemistry In facilitated diffusion, glucose movement follows a concentration gradient, that is, from a high glucose concentration to a lower one. For example, GLUT-1, GLUT -3, and GLUT-4 are primarily involved in glucose uptake from the blood. In contrast, GLUT-2, which is found in the liver and kidney, can either transport glucose into these cells when blood glucose levels are high, or transport glucose from these cells when blood glucose levels are low (for example, during fasting). [Note: GLUT-2 is also found in pancreatic β cells.] GLUT-5 is unusual in that it is the primary transporter for fructose (instead of glucose) in the small intestine and the testes.

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#### Annotation 1767290047756

 #Biochemistry This is an energy-requiring process that transports glucose “against” a concentration gradient—that is, from low glucose concentrations outside the cell to higher concentrations within the cell. This system is a carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na + , which is transported into the cell at the same time. The carrier is a sodium-depen- dent–glucose transporter or SGLT. This type of transport occurs in the epithelial cells of the intestine (see p. 87), renal tubules, and choroid plexus. [Note: The choroid plexus, part of the blood brain barrier, also contains GLUT-1.]

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#### Annotation 1767292407052

 #Biochemistry The conversion of glucose to pyruvate occurs in two stages (Figure 8.11). The first five reactions of glycolysis correspond to an energy investment phase in which the phosphorylated forms of intermediates are synthesized at the expense of ATP. The subsequent reactions of glycolysis constitute an energy generation phase in which a net of two mole cules of ATP are formed by substrate-level phosphorylation (see p. 102) per glucose molecule metabolized.

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#### Annotation 1767294766348

 Phosphorylated sugar molecules do not readily penetrate cell mem- branes, because there are no specific transmembrane carriers for these compounds, and because they are too polar to diffuse through the lipid core of membranes. The irreversible phosphorylation of glu- cose (Figure 8.12), therefore, effectively traps the sugar as cytosolic glucose 6-phosphate, thus committing it to further metabolism in the cell. Mammals have several isozymes of the enzyme hexokinase that catalyze the phosphorylation of glucose to glucose 6-phosphate

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#### Annotation 1767297125644

 #Biochemistry In most tissues, the phosphorylation of glucose is catalyzed by hexokinase , one of three regulatory enzymes of glycolysis (see also phosphofructokinase and pyruvate kinase ). Hexokinase has broad substrate specificity and is able to phos- phorylate several hexoses in addition to glucose. Hexokinase is inhibited by the reaction product, glucose 6-phosphate, which accumulates when further metabolism of this hexose phosphate is reduced. Hexokinase has a low K m (and, therefore, a high affin- ity, see p. 59) for glucose. This permits the efficient phosphoryla- tion and subsequent metabolism of glucose even when tissue concentrations of glucose are low (Figure 8.13). Hexokinase , however, has a low V max for glucose and, therefore, cannot sequester (trap) cellular phosphate in the form of phosphorylated hexoses, or phosphorylate more sugars than the cell can use.

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#### Annotation 1767299484940

 #Biochemistry In liver parenchymal cells and β cells of the pan- creas, glucokinase (also called hexokinase D , or type IV ) is the predominant enzyme responsible for the phosphorylation of glu- cose. In β cells, glucokinase functions as the glucose sensor, determining the threshold for insulin secretion (see p. 310). In the liver, the enzyme facilitates glucose phosphorylation during hyper- glycemia. [Note: Hexokinase also serves as a glucose sensor in neurons of the hypothalamus, playing a key role in the adrenergic response to hypoglycemia

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#### Annotation 1767301844236

 #Biochemistry Glucokinase differs from hexokinase in several impor- tant properties. For example, it has a much higher K m , requiring a higher glucose concentration for half-saturation (see Figure 8.13). Thus, glucokinase functions only when the intracellular concentration of glucose in the hepatocyte is elevated, such as during the brief period following consumption of a carbohy- drate-rich meal, when high levels of glucose are delivered to the liver via the portal vein. Glucokinase has a high V max , allow- ing the liver to effectively remove the flood of glucose delivered by the portal blood. This prevents large amounts of glucose from entering the systemic circulation following a carbohydrate- rich meal, and thus minimizes hyperglycemia during the absorptive period. [Note: GLUT-2 insures that blood glucose equilibrates rapidly across the membrane of the hepatocyte.]

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#### Annotation 1767304203532

 #Biochemistry Glucokinase activity is not directly inhibited by glucose 6-phos- phate as are the other hexokinases , but rather is indirectly inhibited by fructose 6-phosphate (which is in equilibrium with

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#### Annotation 1767306562828

 #Biochemistry glucose 6-phosphate, a product of glucokinase ), and is indi- rectly stimulated by glucose (a substrate of glucokinase ) via the following mechanism. Glucokinase regulatory protein (GKRP) in the liver regulates the activity of glucokinase through reversible binding. In the presence of fructose 6- phosphate, glucokinase is translocated into the nucleus and binds tightly to the regulatory protein, thus rendering the enzyme inactive (Figure 8.14). When glucose levels in the blood (and also in the hepatocyte, as a result of GLUT-2) increase, glucokinase is released from the regulatory protein, and the enzyme re-enters the cytosol where it phosphorylates glucose to glucose 6-phosphate. [Note: Fructose 1-phosphate inhibits formation of the glucokinase -GKRP complex.] Glucokinase functions as a glucose sensor in the maintenance of blood glucose homeosta- sis. Mutations that decrease the activity of glu- cokinase are the cause of a rare form of dia- betes, maturity onset diabetes of the young type 2 (MODY 2).

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#### Annotation 1767308922124

 #Biochemistry The irreversible phosphorylation reaction catalyzed by phospho - fructokinase-1 ( PFK-1 ) is the most important control point and the rate-limiting and committed step of glyco l ysis (Figure 8.16). PFK-1 is controlled by the available concentrations of the substrates ATP and fructose 6- phosphate, and by regulatory substances described below. 1. Regulation by energy levels within the cell: PFK-1 is inhibited allosterically by elevated levels of ATP, which act as an “energy- rich” signal indicating an abundance of high-energy compounds. Elevated levels of citrate, an intermediate in the TCA cycle (see p. 109), also inhibit PFK-1 . Conversely, PFK-1 is activated alloster- ically by high concentrations of AMP, which signal that the cell’s energy stores are depleted. [Note: Citrate inhibition favors the use of glucose for glycogen synthesis, see p.125.] 2. Regulation by fructose 2,6-bisphosphate: Fructose 2,6-bisphos- phate is the most potent activator of PFK-1 (see Figure 8.16), and is able to activate the enzyme even when ATP levels are high. Fructose 2,6-bisphosphate is formed by phosphofructokinase-2 ( PFK-2 ), an enzyme different than PFK-1 . PFK-2 is a bifunctional protein that has both the kinase activity that produces fructose 2,6-bisphosphate and a phosphatase activity that dephosphory- lates fructose 2,6-bisphosphate back to fructose 6-phosphate. In liver, the kinase domain is active if dephosphorylated and is inac- tive if phosphorylated (Figure 8.17). [Note: Fructose 2,6-bisphos

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#### Annotation 1767311281420

 #Biochemistry phate is an inhibitor of fructose 1,6-bisphosphatase , an enzyme of gluconeogenesis (see p. 120 for a discussion of the regulation of gluconeogenesis). The reciprocal actions of fructose 2,6-bisphos- phate on glycolysis (activation) and gluconeogenesis (inhibition) ensure that both pathways are not fully active at the same time, preventing a futile cycle in which glucose would be converted to pyruvate followed by resynthesis of glucose from pyruvate.]

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#### Annotation 1767313640716

 #Biochemistry During the well-fed state: Decreased levels of glucagon and elevated levels of insulin, such as occur following a carbohydrate- rich meal, cause an increase in fructose 2,6-bis- phosphate and, thus, in the rate of glycolysis in the liver (see Figure 8.17). Fructose 2,6-bisphosphate, therefore, acts as an intracellular signal, indicating that glucose is abundant.

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#### Annotation 1767316000012

 #Biochemistry During starvation: Elevated levels of glucagon and low levels of insulin, such as occur during fasting (see p. 327), decrease the intracellular concentration of hepatic fructose 2,6-bisphos- phate. This results in a decrease in the overall rate of glycolysis and an increase in gluconeogenesis.

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#### Annotation 1767318359308

 #Biochemistry Aldolase cleaves fructose 1,6-bisphosphate to dihydroxy acetone phosphate and glyceraldehyde 3-phosphate (see Figure 8.16). The reaction is reversible and not regulated. [Note: Aldolase B , the iso- form in the liver and kidney, also cleaves fructose 1-phosphate, and functions in the metabolism of dietary fructose

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#### Annotation 1767320718604

 #Biochemistry Isomerization of dihydroxyacetone phosphate Triose phosphate isomerase interconverts dihydroxyacetone phos- phate and glyceraldehyde 3-phosphate (see Figure 8.16). Dihydro xy - acetone phosphate must be isomerized to glycer aldehyde 3-phosphate for further metabolism by the glycolytic pathway. This isomerization results in the net production of two molecules of glycer - aldehyde 3-phosphate from the cleavage products of fructose 1,6- bisphosphate.

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#### Annotation 1767325175052

 #Biochemistry Oxidation of glyceraldehyde 3-phosphate The conversion of glyceraldehyde 3-phosphate to 1,3-bisphospho- glycerate by glyceraldehyde 3-phosphate dehydrogenase is the first oxidation-reduction reaction of glycolysis (Figure 8.18). [Note: Because there is only a limited amount of NAD + in the cell, the NADH formed by this reaction must be reoxidized to NAD + for gly- colysis to continue. Two major mechanisms for oxidizing NADH are: 1) the NADH-linked conversion of pyruvate to lactate (anaerobic, see p. 96), and 2) oxidation of NADH via the respiratory chain (aero- bic, see p. 75). The latter requires substrate shuttles (see p. 79.]

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#### Annotation 1767327534348

 #Biochemistry Synthesis of 1,3-bisphosphoglycerate (1,3-BPG): The oxidation of the aldehyde group of glyceraldehyde 3-phosphate to a carboxyl group is coupled to the attachment of P i to the carboxyl group. The high-energy phosphate group at carbon 1 of 1,3-BPG con- serves much of the free energy produced by the oxidation of glyceraldehyde 3-phosphate. The energy of this high-energy phosphate drives the synthesis of ATP in the next reaction of glycolysis.

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#### Annotation 1767329893644

 #Biochemistry Mechanism of arsenic poisoning: The toxicity of arsenic is explained primarily by the inhibition of enzymes such as pyruvate dehydrogenase , which require lipoic acid as a coenzyme (see p. 110). However, pentavalent arsenic (arsenate) also can prevent net ATP and NADH production by glycolysis, without inhibiting the pathway itself. The poison does so by competing with inor- ganic phosphate as a substrate for glyceraldehyde 3-phosphate dehydrogenase , forming a complex that spontaneously hydrolyzes to form 3-phosphoglycerate (see Figure 8.18). By bypassing the synthesis of and phosphate transfer from 1,3- BPG, the cell is deprived of energy usually obtained from the gly- colytic pathway. [Note: Arsenic also replaces P i on the F 1 domain of ATP synthase (see p. 78), resulting in formation of ADP-arsen- ate that is rapidly hydrolyzed.]

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#### Annotation 1767332252940

 #Biochemistry Synthesis of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells: Some of the 1,3-BPG is converted to 2,3-BPG by the action of bisphosphoglycerate mutase (see Figure 8.18). 2,3-BPG, which is found in only trace amounts in most cells, is present at high con- centration in red blood cells (increases O 2 delivery, see p. 31). 2,3-BPG is hydrolyzed by a phosphatase to 3-phosphoglycerate, which is also an intermediate in glycolysis (see Figure 8.18). In the red blood cell, glycolysis is modified by inclusion of these “shunt” reactions.

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#### Annotation 1767334612236

 #Biochemistry Synthesis of 3-phosphoglycerate producing ATP When 1,3-BPG is converted to 3-phosphoglycerate, the high-energy phosphate group of 1,3-BPG is used to synthesize ATP from ADP (see Figure 8.18). This reaction is catalyzed by phosphoglycerate kinase , which, unlike most other kinases , is physiologically reversible. Because two molecules of 1,3-BPG are formed from each glucose molecule, this kinase reaction replaces the two ATP molecules con- sumed by the earlier formation of glucose 6-phosphate and fructose 1,6-bisphosphate. [Note: This is an example of substrate-level phos- phoryl ation, in which the energy needed for the production of a high- energy phosphate comes from a substrate rather than from the electron transport chain (see J. below and p. 113 for other examples).]

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#### Annotation 1767336971532

 #Biochemistry Dehydration of 2-phosphoglycerate The dehydration of 2-phosphoglycerate by enolase redistributes the energy within the 2-phosphoglycerate molecule, resulting in the for- mation of phosphoenolpyruvate (PEP), which contains a high- energy enol phosphate (see Figure 8.18). The reaction is reversible despite the high-energy nature of the product

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#### Annotation 1767339330828

 #Biochemistry Formation of pyruvate producing ATP The conversion of PEP to pyruvate is catalyzed by pyruvate kinase , the third irreversible reaction of glycolysis. The equilibrium of the pyru- vate kinase reaction favors the formation of ATP (see Figure 8.18). [Note: This is another example of substrate-level phosphorylation.] 1. Feed-forward regulation: In liver, pyruvate kinase is activated by fructose 1,6-bisphosphate, the product of the phosphofructo kinase reaction. This feed-forward (instead of the more usual feedback) regulation has the effect of linking the two kinase activities: increased phosphofructokinase activity results in elevated levels of fructose 1,6-bisphosphate, which activates pyruvate kinase . 2. Covalent modulation of pyruvate kinase: Phosphorylation by a cAMP-dependent protein kinase leads to inactivation of pyruvate kinase in the liver (Figure 8.19). When blood glucose levels are low, elevated glucagon increases the intracellular level of cAMP, which causes the phosphorylation and inactivation of pyruvate kinase . Therefore, PEP is unable to continue in glycoly- sis, but instead enters the gluconeogenesis pathway. This, in part, explains the observed inhibition of hepatic glycolysis and stimulation of gluconeogenesis by glucagon. Dephos phorylation of pyruvate kinase by a phosphoprotein phosphatase results in re activation of the enzyme. 3. Pyruvate kinase deficiency: The normal, mature erythrocyte lacks mitochondria and is, therefore, completely dependent on glycoly- sis for production of ATP. This high-energy compound is required to meet the metabolic needs of the red blood cell, and also to fuel the pumps necessary for the maintenance of the biconcave, flexi-

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#### Annotation 1767341690124

 #Biochemistry ble shape of the cell, which allows it to squeeze through narrow capillaries. The anemia observed in glycolytic enzyme deficien- cies is a consequence of the reduced rate of glycolysis, leading to decreased ATP production. The resulting alterations in the red blood cell membrane lead to changes in the shape of the cell and, ultimately, to phagocytosis by the cells of the reticuloendothelial system, particularly macrophages of the spleen. The premature death and lysis of red blood cells results in hemolytic anemia. Among patients exhibiting the rare genetic defects of glycolytic enzymes, about 95% show a deficiency in pyruvate kinase , and 4% exhibit phosphoglucose isomerase deficiency. PK deficiency is restricted to the erythrocytes, and produces mild to severe chronic hemolytic anemia (erythrocyte destruction), with the severe form requiring regular cell transfusions. The severity of the disease depends both on the degree of enzyme deficiency (gen- erally 5–25% of normal levels), and on the extent to which the individual’s red blood cells compensate by synthesizing increased levels of 2,3-BPG (see p. 31). Almost all individuals with PK defi- ciency have a mutant enzyme that shows abnormal properties— most often altered kinetics (Figure 8.20).

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#### Annotation 1767346146572

 #Biochemistry Lactate, formed by the action of lactate dehydrogenase , is the final product of anaerobic glycolysis in eukaryotic cells (Figure 8.21). The formation of lactate is the major fate for pyruvate in lens and cornea of the eye, kidney medulla, testes, leukocytes and red blood cells, because these are all poorly vascularized and/or lack mitochondria. 1. Lactate formation in muscle: In exercising skeletal muscle, NADH production (by glyceraldehyde 3-phosphate dehydrog enase and by the three NAD + -linked dehydrogenases of the citric acid cycle, see p. 112) exceeds the oxidative capacity of the respiratory chain. This results in an elevated NADH/NAD + ratio, favoring reduction of pyruvate to lactate. Therefore, during intense exer- cise, lactate accumulates in muscle, causing a drop in the intra- cellular pH, potentially resulting in cramps. Much of this lactate eventually diffuses into the bloodstream, and can be used by the liver to make glucose (see p. 118). 2. Lactate consumption: The direction of the lactate dehydrog enase reaction depends on the relative intracellular concentrations of pyruvate and lactate, and on the ratio of NADH/NAD + in the cell. For example, in liver and heart, the ratio of NADH/NAD + is lower than in exercising muscle. These tissues oxidize lactate (obtained from the blood) to pyruvate. In the liver, pyruvate is either con- verted to glucose by gluconeogenesis or oxidized in the TCA cycle. Heart muscle exclusively oxidizes lactate to CO 2 and H 2 O via the citric acid cycle.

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#### Annotation 1767348505868

 #Biochemistry Lactic acidosis: Elevated concentrations of lactate in the plasma, termed lactic acidosis, occur when there is a collapse of the circu- latory system, such as in myocardial infarction, pulmonary embolism, and uncontrolled hemorrhage, or when an individual is in shock. The failure to bring adequate amounts of oxygen to the tissues results in impaired oxidative phosphorylation and decreased ATP synthesis. To survive, the cells use anaerobic glycolysis as a backup system for generating ATP, producing lac- tic acid as the endproduct. [Note: Production of even meager amounts of ATP may be life-saving during the period required to reestablish adequate blood flow to the tissues.] The excess oxy- gen required to recover from a period when the availability of oxy- gen has been inadequate is termed the oxygen debt.

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#### Annotation 1767350865164

 #Biochemistry Anaerobic glycolysis: Two molecules of ATP are generated for each molecule of glucose converted to two molecules of lactate (Figure 8.22). There is no net production or consumption of NADH. 2. Aerobic glycolysis: The direct consumption and formation of ATP is the same as in anaerobic glycolysis—that is, a net gain of two ATP per molecule of glucose. Two molecules of NADH are also produced per molecule of glucose. Ongoing aerobic glycolysis requires the oxidation of most of this NADH by the electron trans- port chain, producing approximately three ATP for each NADH molecule entering the chain

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#### Annotation 1767353224460

 #Biochemistry The regulation of glycolysis by allosteric activation or inhibition, or the phosphorylation/dephosphorylation of rate-limiting enzymes, is short- term—that is, they influence glucose consumption over periods of min- utes or hours. Superimposed on these moment-to-moment effects are slower, and often more profound, hormonal influences on the amount of enzyme protein synthesized. These effects can result in 10-fold to 20- fold increases in enzyme activity that typically occur over hours to days. Although the current focus is on glycolysis, reciprocal changes occur in the rate-limiting enzymes of gluconeogenesis, which are described in

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#### Annotation 1767355583756

 #Biochemistry Regular consumption of meals rich in carbo - hydrate or administration of insulin initiates an increase in the amount of glucokinas e, phosphofructokinase , and pyruvate kinase in liver (Figure 8.23). These changes reflect an increase in gene transcription, resulting in increased enzyme synthesis. High activity of these three enzymes favors the conversion of glucose to pyruvate, a characteristic of the well- fed state (see p. 321). Conversely, gene transcription and synthesis of glucokinase , phosphofructokinase, and pyruvate kinase are decreased when plasma glucagon is high and insulin is low, for example, as seen in fasting or diabetes.

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#### Annotation 1767357943052

 #Biochemistry VII. ALTERNATE FATES OF PYRUVATE A. Oxidative decarboxylation of pyruvate Oxidative decarboxylation of pyruvate by pyruvate dehydrogenase complex is an important pathway in tissues with a high oxidative capacity, such as cardiac muscle (Figure 8.24). Pyruvate dehydro- genase irreversibly converts pyruvate, the end product of glycolysis, into acetyl CoA, a major fuel for the TCA cycle (see p. 109) and the building block for fatty acid synthesis (see p. 183). B. Carboxylation of pyruvate to oxaloacetate Carboxylation of pyruvate to oxaloacetate (OAA) by pyruvate carboxylase is a biotin-dependent reaction (see Figure 8.24). This reaction is important because it replenishes the citric acid cycle inter- mediates, and provides substrate for gluconeogenesis (see p. 118). C. Reduction of pyruvate to ethanol (microorganisms) The conversion of pyruvate to ethanol occurs by the two reactions summarized in Figure 8.24. The decarboxylation of pyruvate by pyruvate decarboxylase occurs in yeast and certain other micro - organisms, but not in humans. The enzyme requires thiamine pyro - phosphate as a coenzyme, and catalyzes a reaction similar to that described for pyruvate dehydrogenase (see p. 110).