9 AA metabolism 2 Flashcards

1
Q

what is protein turnover?

A

the degradation and resynthesis of proteins

proteins have a finite shelf life - have to be degraded and new ones made

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2
Q

How can AA be generated?

A
  • can be synthesized (other deck)
  • digestion of proteins in the intestine
  • degradation of proteins within the cell
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3
Q

How stable are proteins?

A
  • some are very stable, crystallin in eye lens can last more than 70 years
  • but many proteins are short lived, especially those important in metabolic regulation
  • changing the amount of these proteins can change the metabolic patterns
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4
Q

How do we know when to degrade proteins in cells?

A

cells have mechanisms for detecting and removing damaged proteins

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5
Q

What are processes regulated by protein degradation?

A
  • gene transcription
  • organ formation
  • tumor suppression
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6
Q

In animals, under what 3 circumstances do AA undergo degradation?

A
  1. when AA are not needed for new protein synthesis (there is surplus)
  2. when the ingested AA exceed the body’s needs for protein synthesis
  3. when carbohydrates are not available as fuel during starvation or uncontrolled diabetes mellitus, use AA as energy insead, degrade into glucose
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7
Q

where does degradation of AA occur?

A

in the liver

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8
Q

What are the 2 main steps of AA degredation?

A
  • the amino group is removed
  • the carbon skeletal (α-ketoacids) are metabolized to enter back into the mtabolic mainstream, try to feed back into TCA cycle
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9
Q

what happens to the removed amino group from AA?

A
  • the amino group of AA are transferred to α-ketoglutarate (backbone for glutamate) to form glutamate
  • reaction is catalysed by aminotransferases
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10
Q

does aminotransferase used for degradation or biosynthesis?

A

both!

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11
Q

What is the reverse reaction of glutamate biosynthesis?

A

degradation of glutamate
same enzyme glutamate dehydrogenase is used

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12
Q

Is ammonia safe to animal tissue?

A

no its toxic if we let is accumulate

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13
Q

Where can ammonia formed in tissue go?

A

ammonia formed in tissue other than the liver (extrahepatic tissue) are converted to non-toxic forms before exported to blood and transported to liver or kidneys

(extrahepatic tissue) - outside liver

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14
Q

How can ammonia be transported in the blood? where does it go?

A

free ammonia produced in tissues combine with glutamate to form glutamine via a 2 step reaction

glutamine is then transported to liver for processing, releasing the ammonia

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15
Q

How is ammonia disposed of?

A

by urea synthesis in urea cycle

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16
Q

What are 2 ways that amino groups from degraded AA can be collected?

A
  1. amino groups collected in the form of glutamate and glutamate can be converted to glutamine and that is transported to the liver
  2. alanine transports amino groups from muscles to liver via the **glucose-alanine cycle **
17
Q

What is the glucose-alanine cycle?

A
  • the amino group from glutamate can be transferred to pyruvate to form alanine
  • pyruvate is readily supplied from muscle glycolysis
  • then alanine is transported to the liver in blood
  • in the liver cytosol, the amino group of alanine is transferred to α-ketoglutarate to form pyruvate and glutamate
  • pyruvate can be converted to glucose via gluconeogenesis and fed back to muscle as fuel
  • glutamate can then enter the mitochondria, the ammonium ion then disposed of by urea synthesis
18
Q

What is converted to urea by the urea cycle?

A

ammonia deposited in the mitochondria of hepatocytes

19
Q

What happens to the urea produced by the urea cycle?

A

the urea produced is then passed to the bloodstream to be carried to the kidneys

and excreted into urine

20
Q

Where does the urea cycle begin and span across?

A

begin in mitochondria and spans the liver mitochondria and cytosol

starts in mitochondria -> cytosol -> back into the mitochondria

21
Q

How is the ammonia ion in the liver mitochondria prepped before going in to the urea cycle?

A

the NH₄+ in the liver mitochondria is used to form carbamoyl phosphate

  • carboamoyl phosphate enters the urea cycle
22
Q

What are the 4 steps of urea cycle?

A
  1. citrulline is formed from carbomyl phosphate (entry of 1st amino group) and ornithine
  2. citrulline then passes through to the cytosol, reacts with aspartate (entry of 2nd amino group) to form argininosuccinate
  3. argininosuccinate is cleaved to form arginine and fumarate. fumarate is linked back to the TCA cycle (link between urea cycle and TCA cycle)
  4. arginine is cleaved to form ornithine and urea. ornithine is transported back to the mitochondria for the urea cycle
23
Q

How is the urea cycle linked to the TCA cycle?

A

via aspartate-arginosuccinate shunt of the citric acid cycle

the fumerate from urea cycle can be converted to malate

24
Q

What are the fates of fumarate synthesized by the urea cycle?

A
  1. fumarate is hydrated to malate
  2. malate is oxidised to oxaloacetate
  3. oxaloacetate has these possible fates:
    * transminated to aspartate
    * conerted to glucose via the gluconeogenic pathway as part of bypass 1: conversion of pyruvate to phosphoenolpyruvate
    * condensed with acetyl coA to form citrate
    * converted to pyruvate
25
Q

What are the fates of carbon skeletons of amino acids after amino group removal?

A

can be processed to become intermediates of the citric acid cycle

either glucogenic or ketogenic

26
Q

What are the end products of amino acid degradation?

A

intermediates of the central metabolic pathway

27
Q

What is the difference between ketogenic and glucogenic AA?

A

ketogenic AA can be converted to ketone bodies or most likely acetyl coA
glucogenic AA can be converted to glucose

some can be both

28
Q

what are examples of ketogenic, glucogenic and both AA?

A

ketogenic: Leu and Lys
glucogenic: Glu and Gln
both: Try Trp