Amino acid catabolism Flashcards
What is the trend with protein intake
Amount of protein we intake is increasing
Most AA are metabolized in
The liver
Amino acids can be metabolized through
Amino group and urea cycle
And citric acid cycle
What happens with ammonia and carbon skeleton in principle
Ammonia- recycled or excreted
Carbon skeleton- TCA cycle or Glucoenogenesis or ketogenesis
In what parts of GI protein is digested
Stomach and small intestine
What enzymes degrade protein
Peptin
HCl to unwind
Trypsin
Chemotrypsin
What is the first reaction of amino acids catabolism
Removal of an amino group
Describe how removal of the amino group happens
Through amino transferase alpha-ketoglutarate is transformed to L-glutamate
What is the effect on amino acids during transamination reaction
No net loss, it is just transferred from one molecule to another
Aminotransferases are ___
AA specific ( e.g. alanine amino transferase)
What is the cofactor for amino-transferases
Pyridoxal phosphate (vit.6)
Vitamin 6 is also a cofactor for
Glycogen phosphorylase
What is the function of L-glutamate
The glutamate then functions as an
amino group donor for biosynthetic pathways or for excretion pathways that lead to the elimination of
nitrogenous waste products.
Deanimation of glutamate happens in
Mitochondria
What enzyme, product and substrates are needed for deanimation reaction in liver
Glumate-> alpha-ketoglutarate
Enzyme: glutamate dehydrogenase
Using: NAD(P)+, H2O
The use of alpha-ketoglutarate
Used for transamination, TCA cycle or glucoeneogenesis
Most tissues send their amino group in the form of___
Glutamine
Explain transport of ammonia from other tissues
L-glutamate with glutamine synthase is converted to gamma-Glutamyl phosphate ( in all tissues)
with glutamine synthetase gamma-Glutamyl phosphate is converted to L-glutamine
L-glutamine is transported to the liver
Glitaminase in liver mitochodria converts L-glutamine to L-glutamate
All deanimmation reaction happen in
The liver
What muscles have an addition to glutamate transport system
Muscles send amino groups also through alanine
When alanine gets to the liver it is converted back to pyruvate in the liver, and then pyruvate can go through glucoenogenesis and glutamate-> urea cycle
how muscles get alanine
By converting pyruvate to alanine with alanine aminotransferase
Excretion of amino group happens through
Urea cycle
Where does urea cycle begin and where it continues
Starts in mitochondria and continues in the cytoplasm
What are possible sources for urea to urea cycle
Ammonia from intestine (bacterial digestion and amino acid metabolism)
Glutamine
Glutamate ( also from alanine)
What happens in before urea cycle in mitochondria
Ammonia group (NH4+) is carboxylated and phosphated with carbamoyl phosphate synthetase I
How many energy is required for the synthesis of carbomoyl phosphate
requires 2 ATPs ( one for enzymatic reaction) and one for addition of a phosphate group
what happens in parallel to glutamate converting to alpha-ketoglutarate and donating its NH4+ group
Liver cells have TCA cycle itself. So they produce oxaloacetate that is converted to aspartate with aspertate aminotransferase
Happens in mitochondria
What happens to carbomyl phosphate
It combines with ornithine to yield citrulline with the help of ornitine trans-carbamoylase
what happen to citrulline
It goes out of the mitochondria, where arginosuccinate synthetase through an intermediate converts to arginosuccinate
What two things are required for the step of conversion citrulline to arginosuccinate
ATP
And aspartate
What happens to arginosuccinate
It is broken down into fumarate ( can be used in TCA) and arginine with arginosuccinase
What happens to arginine
Using arginase, ornithine is synthesized producing urea
Urea has how many amino groups and from what sources
2 amino groups
1 from glutamate ->citrulline (from various tissues)
1 from aspartate (TCA cycle in the liver)
How urea cycle is regulated
When acetyl-CoA and glutamate are high - synthesize of N-acetylglutamate
N-acetylglutamate has positive effect on carbomyl phosphate synthetase I
Expression of urea cycle enzymes increases during
High protein diet ( some AA yield acetyl-CoA in the result of metabolism)
Starvation,tumor, uncontrolled diabetes (body starts to metabolize muscles and protein in the body)
Urea cycle cannot continue without
The TCA cycle running,because of aspartate, coming from oxaloacetate
How fumarate is brought to TCA cycle in mitochodria from cytoplasm
Fumurate is converted to malate with fumarase , malate comes in mitochondria and it can be integrated in TCA cycle
With what enzyme malate can be converted to oxaloacetate
Malate dehydrogenase
Where fumurase and malate dehydrogenase are found
Both in cytoplasm and in mitochondria
Amino acids yielding acetyl-CoA are
ketogenic
amino acids yielding other end products are
Glucogenic
After amino group is removed what happens
Carbon backbone serves as an intermediate for TCA cycle
Amino acids that are both glucogenic and ketogenic
Isoleucine Pnenylalanine Threonine Tryptophan Tyrosine
What amino acids are only ketogenic ( do not yield glucose)
Lysine and leucine
Pyruvate can be obtained from what AAs
From alanine Tryptophan Cysteine Serine Glycine Threonine
Acetyl-CoA can be obtained from what AAs
Tryptophan Lysine Phenylalanine Tyrosine Leucine Isoleucine Threonine
alpha-ketogluterate can be obtained from what AAs
Proline Glutamate Glutamine Arginine Histidine
Succinyl-CoA can be obtained from what amino acids
Methionine
Isoleucine
Threonine
Valine
Oxaloacetate can be obtained from what amino acids
Asparagine
Aspartate
Fumurate can be obtained from what amino acids
Phenyalanine
Tyrosine
What makes Leucine, Isoleucine and Valine a group
They are used as fuel in muscle/adipose tissue/brain
They are called Branched chain amino acids
Branched chain aminotransferase is only expressed in
Extra-hepatic cells ( outisde liver)
How glutamate dehydrogenase is regulated
Increased by ADP and decreased by GTP
How urea cycle is regulated
All four enzymes of urea cycle and carbomoyl phosphate synthase I are regulated by nutritional status (diet and starvation)
High energy demand of urea cycle is offset
by NADH (2.5 ATP) when malate is cinverted back to oxaloacetate
