4. Key intermediates and some characteristic reactions in degradation of amino acids and those of biosynthesis of non-essential aa's

where are most of the aa’s metabolised?

in the liver

which aa’s are exclusively metabolized in muscle?

branched chain aa: leucine, isoleucine and valine

what kind of enzymes catalyze the switching of the amino group from the carbon skeleton?

by aminotransferases

aminotransferase?

enzymes which switches the amino group with an ⍺-keto group

what do the aminotransferase need for proper function?

PLP

PLP?

derived from vitamin B6

accepts and donates the amnio group in chemical reactions, this is accomplished by a ping-pong reaction mechanism

how is the amino group removed from glutamate?

removed from the glutamate in a reaction catalyzed by glutamate dehydrogenase

special reaction, where both NAD+ or NADP+ can be used

the reaction is an oxidative deamination reaction

which aminoacids does not need an aminotransferase?

serine and threonine does not need aminotransferases, their amino group is non-oxidatively removed by serine/threonine dehydratase

this reaction requires PLP

what are the fates of the amnio group?

can be excreted through the urea cycle

can be used to synthesize new biomolecules

* new amino acids
* nucleotides
* biological amines (histamine, dopamine, melatonin)

describe how aminoacids are excreted to the urea cycle?

in case they are broken in liver: ammonium directly excreted through urea cycle

in extrahepatic cycle: go to liver where it will enter the urea cycle

ammonium is incorporated into glutamine, by glutamine synthetase reaction

where does the glutaminase reaction take place? what does it do?

only in liver mitochondria

converts glutamine into glutamate and ammonium

what are the fate of the carbon skeleton?

depends on wether they are ketogenic, glucogenic or both

* ketogenic: can be substrates for ketone body synthesis
* glucogenic: can be substrates for gluconeogenesis

ketogenic amino acids?

their carbon skeleton is metabolised into acetyl-CoA

lysine and leucine

glucogenic amino acids?

carbon skeleton is metabolised into pyruvate or any of the intermediates of the TCA cycle

\
* aspargine
* aspartate
* methionine
* valine
* arginine
* glutamine
* glutamate
* histidine
* proline

mixed amino acids?

carbon skeleton can enter two different pathways, one yielding acetyl-coa and one yielding a glucogenic substrate

\
* alanine
* tryptophan
* phenylalanine
* tyrosine
* threonine
* isoleucine
* cystein
* glycine
* serin

essential amino acids?

those who the body is unable to synthesize by itself, so they have to be acquired through diet

\
* histidine
* isoleucine
* leucine
* lysine
* methionine
* phenylalanine
* threonine
* tryptophan
* valine

non-essential amino acids?

those amino acis our body is able to synthesize in large amounts

\
* alanine
* aspartate
* aspargin
* glutamine
* serine

conditionally essential aa?

those aa which can be synthesized in the body, but not always in large enough amounts

\
* proline
* arginine
* glycine
* cysteine
* glutamine
* tyrosine

what are the main classes of reactions involved in biosynthesis of aa’s?

transamination reaction - using PLP

one-carbon group transfers - THF, adoMet

glutamine amidotransferase reactions

PRPP?

5-phosphoribosyl-1-pyrophosphate

important intermediate of the pathway of histidine and tryptophan

describe biosynthesis of glutamate

glutamate is synthetized by transamination of ⍺-ketogluterate, often by ALT or AST

it can be synthetized by glutamate DH, but this pathway is less important in humans

describe biosynthesis of glutamine?

synthetized from ammonia and glutamate by glutamine synthetase

glutamine synthethase is allosterically regulated by 8 molecules, all of which are downstream products = neg. feedback

* if one or some are present, it gives partial inhibition
* all 8 shuts down the enzyme
* glycine, alenine, AMP, tryptophan, Carbanoyl P, CTP, histidine, glucosamine-6-P

it can also covalently regulated by adenylation

biosynthesis of proline?

from glutamate in bacteria

from arginine in humans

biosynthesis of arginine

synthetized from glutamate

glutamate is converted into ornithine, which enters urea cycle

arginine is an intermediate of urea cycle

biosynthesis of glycine, cysteine and serine

serine is synthetized from 3-phosphoglycerate in a 3-step process

serine can be converted into glycine in a one step process

serine and homeocysteine can be converted to cystathione by cystathione β-synthase

one more reaction converts cystathione into cysteine

biosynthesis of alanine, aspartate and aspargine

alanine and aspartate are produced by alanine and aspartate aminotransferase, from pyruvate and OAA respectively

aspargine is synthetized from glutamine amidotransferase which transfers the amino group from glutamine to aspartate, forming aspargine

biosynthesis of tyrosine?

tyrosine is formed from phenylalanin by phenylalanin hydroxylase reaction

how can we regulate amino acid synthesis?

allosterically

the rate-limiting enzyme is usually the first in the sequence of synthesis

it is usually inhibited by the final product in a feedback mechanism