9 AA metabolism 2 Flashcards
what is protein turnover?
the degradation and resynthesis of proteins
proteins have a finite shelf life - have to be degraded and new ones made
How can AA be generated?
- can be synthesized (other deck)
- digestion of proteins in the intestine
- degradation of proteins within the cell
How stable are proteins?
- 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
How do we know when to degrade proteins in cells?
cells have mechanisms for detecting and removing damaged proteins
What are processes regulated by protein degradation?
- gene transcription
- organ formation
- tumor suppression
In animals, under what 3 circumstances do AA undergo degradation?
- when AA are not needed for new protein synthesis (there is surplus)
- when the ingested AA exceed the body’s needs for protein synthesis
- when carbohydrates are not available as fuel during starvation or uncontrolled diabetes mellitus, use AA as energy insead, degrade into glucose
where does degradation of AA occur?
in the liver
What are the 2 main steps of AA degredation?
- 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
what happens to the removed amino group from AA?
- the amino group of AA are transferred to α-ketoglutarate (backbone for glutamate) to form glutamate
- reaction is catalysed by aminotransferases
does aminotransferase used for degradation or biosynthesis?
both!
What is the reverse reaction of glutamate biosynthesis?
degradation of glutamate
same enzyme glutamate dehydrogenase is used
Is ammonia safe to animal tissue?
no its toxic if we let is accumulate
Where can ammonia formed in tissue go?
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
How can ammonia be transported in the blood? where does it go?
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
How is ammonia disposed of?
by urea synthesis in urea cycle
What are 2 ways that amino groups from degraded AA can be collected?
- amino groups collected in the form of glutamate and glutamate can be converted to glutamine and that is transported to the liver
- alanine transports amino groups from muscles to liver via the **glucose-alanine cycle **
What is the glucose-alanine cycle?
- 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
What is converted to urea by the urea cycle?
ammonia deposited in the mitochondria of hepatocytes
What happens to the urea produced by the urea cycle?
the urea produced is then passed to the bloodstream to be carried to the kidneys
and excreted into urine
Where does the urea cycle begin and span across?
begin in mitochondria and spans the liver mitochondria and cytosol
starts in mitochondria -> cytosol -> back into the mitochondria
How is the ammonia ion in the liver mitochondria prepped before going in to the urea cycle?
the NH₄+ in the liver mitochondria is used to form carbamoyl phosphate
- carboamoyl phosphate enters the urea cycle
What are the 4 steps of urea cycle?
- citrulline is formed from carbomyl phosphate (entry of 1st amino group) and ornithine
- citrulline then passes through to the cytosol, reacts with aspartate (entry of 2nd amino group) to form argininosuccinate
- argininosuccinate is cleaved to form arginine and fumarate. fumarate is linked back to the TCA cycle (link between urea cycle and TCA cycle)
- arginine is cleaved to form ornithine and urea. ornithine is transported back to the mitochondria for the urea cycle
How is the urea cycle linked to the TCA cycle?
via aspartate-arginosuccinate shunt of the citric acid cycle
the fumerate from urea cycle can be converted to malate
What are the fates of fumarate synthesized by the urea cycle?
- fumarate is hydrated to malate
- malate is oxidised to oxaloacetate
- 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
What are the fates of carbon skeletons of amino acids after amino group removal?
can be processed to become intermediates of the citric acid cycle
either glucogenic or ketogenic
What are the end products of amino acid degradation?
intermediates of the central metabolic pathway
What is the difference between ketogenic and glucogenic AA?
ketogenic AA can be converted to ketone bodies or most likely acetyl coA
glucogenic AA can be converted to glucose
some can be both
what are examples of ketogenic, glucogenic and both AA?
ketogenic: Leu and Lys
glucogenic: Glu and Gln
both: Try Trp
