Module 11: Amino Acid Metabolism (Part 01) Flashcards
These are formed through digestion process enters the amino acid pool in the body
Amino Acids
This is the total supply of free amino acids available for use in the human body.
Amino Acid Pool
The amino acid pool is derived from what three (3) sources?
(1) Dietary protein
(2) Protein turnover
(3) Biosynthesis of amino acids in the liver
This is a repetitive process in which the body proteins are degraded and resynthesized
Protein turnover
The amino acid pool is used for what?
(1) protein synthesis = 90%
(2) Synthesis of nitrogen containing compounds
(3) gluconeogenesis (fasting)
(4) ketogenesis (fasting)
(5) energy (fed)
Why do we oxidize amino acids?
(1) protein turnover
(2) diet is rich in protein
(3) starvation and diabetics
This releases amino acids in excess of use in protein synthesis. in this, amino acids are used for energy reservoir and is a source of glucose.
Protein Turnover
How are amino acids not used in protein synthesis important
They are oxidized to form glucose because they have no storage unlike fats and carbohydrates. They are known as the spare glucose.
The Degradation of amino acids involves what?
removal of the a-amino group and degradation of the remaining carbon skeleton.
They act as collection point of amino groups for amino acids.
Glutamate and glutamine
This transports amino groups from skeletal muscle and brings it to the liver.
Alanine
What happens to excess ammonia in the body?
Excess ammonia in most other tissues is converted to glutamine. Glutamine transports amino groups from brain.
Most AA are derived from what
dietary proteins or breakdown of cellular proteins.
Most amino acids are metabolized in the _____
liver, where they are either used for biosynthetic pathways or excreted as urea or uric acid.
For ammonia generated in extrahepatic tissues, they are brought into the liver by _________(muscle) and ________(muscle, brain and other tissues).
alanine and glutamine
Amino acids undergo what?
Amino acids undergo transamination to keto acids. Amino group from amino acid is given to a-ketoglutarate which becomes glutamate. Transamination of alanine (A) forms pyruvate.
Glutamine enters the liver and is deaminated to glutamate by what.
glutaminase
Amino groups from many amino acids are collected in the liver in the form of ____________.
glutamate.
Glutamate from the cytosol goes to the mitochondria where it undergoes what.
undergoes oxidative deamination to a-ketoglutarate (a 5C keto acid) catalyzed by glutamate dehydrogenase
This is the state that results when the amount of nitrogen taken into the human body as protein equals the amount of nitrogen excreted from the body in waste materials.
Nitrogen Balance
In this form of nitrogen imbalance, protein degradation exceeds protein synthesis. Hence the amount of N in urine exceeds nitrogen consumed.
Negative Nitrogen Balance
Where is negative nitrogen balance sprung up?
From tissue wasting, post surgery, advance cancer or diet deficiency
This form of nitrogen imbalance is where the rate of protein synthesis (anabolism) is more than protein degradation (catabolism
Positive nitrogen imbalance
What triggers positive nitrogen imbalance?
Growth, pregnancy and tissue synthesis
The first step in the catabolism of L-amino acids is what
(1) Removal of an alpha amino group by transamination and oxidative deamination
What happens in transamination?
The α-amino group of an amino acid is given to α-ketoglutarate which becomes glutamate, while the remaining C skeleton becomes a keto acid.
These are confined in the liver. If present in the blood in high concentrations is an indication of liver disease.
TRANSAMINASES, SGPT & SGOT
This is the acceptor of amino groups from amino acids.
Glutamate
In many aminotransferase reactions, ___________is the amino group acceptor.
a-ketoglutarate
All aminotransferases have ______________ as cofactor.
pyridoxal phosphate (PLP)
In this, amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia which occurs as ammonium which eventually goes into the urea cycle.
Oxidative deamination
In oxidative deamination, alanine forms what
pyruvate (C3) + NH4+
In oxidative deamination, glutamate forms what
a-ketoglutarate (C5) ) + NH4
In oxidative deamination, aspartate forms what
oxaloacetate (C4) + NH4+
What happens to excess ammonia?
Excess ammonia in tissues is added to glutamate to form glutamine (glutamate synthase). It is then transported in the blood and enters the liver. Inside it is deaminated to glutamate by the enzyme glutaminase
Explain the glucose alanine cycle
Alanine serves as a carrier of ammonia and of the carbon skeleton of pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.
This is catalyzed by glutamate dehydrogenase in which glutamate is converted into alpha-ketoglutarate with the release of an ammonium ion, ion (NH4+)
Oxidative Deamination
What is the goal of oxidative deamination?
To regenerate alpha ketoglutarate
Where dies oxidative deamination occur?
Liver and kidney
Why is glutamate unique?
Glutamate is unique because it is the only amino acid that undergoes rapid oxidative deamination by glutamate dehydrogenase
What is the net effect of amino acid degradation?
The net effect of amino acid degradation is the production of ammonium ion which is toxic.
What happens to ammonium ion?
It is converted to urea (relatively non-toxic compound) in the liver via urea cycle. It is toxic because it depletes the brain of ATP. It combines with a-ketoglutarate, removing it from the Krebs cycle. (cataplerotic)
This is the form of ammonium ions when it is converted to urea and is excreted by terrestrial animals
Ureotelic
This transports ammonia from skeletal muscles.
Alanine
This, in the muscles, liver and nervous system. Conversion to glutamine is the major mechanism for the removal of ammonia in the brain. Circulating glutamine is taken by the liver and kidneys then deaminated by glutaminase to glutamate.
Glutamine
This is made in the liver, goes to blood, to the kidneys then secreted in the urine. This is the excretory form of amino nitrogen in man.
urea
This is almost exclusive to hepatocytes. This reaction uses HCO3 that is a byproduct mitochondrial respiration.
Urea Cycle
This the fuel for urea cycle
Carbamoyl P is the fuel of urea cycle which requires 2 ATP
This converts ammonium and bicarbonate into carbamoyl phosphate. This is the rate-limiting step in the urea cycle. This reaction requires two ATP and occurs in the mitochondria.
Carbamoyl phosphate synthetase
Explain the Urea Cycle begins in the liver mitochondria
Stage 1: Carbamoyl group transfer
The carbamoyl group of carbamoyl phosphate is transferred to ornithine to form citrulline
Stage 2: Citrulline-aspartate condensation
Citrulline is transported into the cytosol, citrulline reacts with aspartate to produce arginosuccinate utilizing ATP
In this reaction the second of two nitrogen atoms of urea is introduced into the cycle (One nitrogen comes from carbamoyl phosphate and the other from aspartate – original source of both is glutamate)
Two ATP equivalents are used in this step
Stage 3: Argininosuccinate cleavage:
Argininosuccinate is cleaved to arginine and fumarate by the enzyme argininosuccinate lyase
This is produced is used in citric acid cycle
Fumarate
This is produced through transamination of oxaloacetate is used in step 2 of the urea cycle as donor of second N of urea.
Aspartate
An amino acid that has a carbon-containing degradation product that can be used to produce glucose via gluconeogenesis.
glucogenic amino acids
This amino acids converted to pyruvate and citric acid cycle intermediates can serve as glucose precursors
glucogenic amino acids
The amino acids converted to acetyl CoA or acetoacetyl CoA can serve as fatty acids and/or ketone body precursors
ketogenic amino acids
An amino acid that has a carbon-containing degradation product that can be used to produce ketone bodies
ketogenic amino acids
Interrelationships among Metabolic Pathways
(1) Feasting (over eating): Causes the body to store a limited amount as glycogen and the rest as fat. (glu ->glycogen, fat -> body fat, Amino group (AA) -> urea
(2) Fasting (no food ingestion): The body uses its stored glycogen (glu for brain) and fat for energy.
(3) Starvation (not eating for a prolonged period):
Glycogen stores are depleted,
Body protein is broken down to amino acids to synthesize glucose.
Fats are converted to ketone bodies (used for energy).
