W10 Amino Acid Metabolism Flashcards
primary function of amino acids
act as monomer unit in protein synthesis
used as substrate for biosynthesis reactions for nitric oxide, hormones (nicotinamide), heme, purine and pyrimidine bases
how does the body obtain amino acids
amino acids cannot be stored in the body
either by:
- dietary intake
- amino acid synthesis
- degradation of pre-existing proteins
amino acid metabolism in fed state
amino acids released by digestion pass from gut through hepatic portal vein to liver
most amino acids used for synthesis of proteins in liver and other tissues
excess amino acids converted to glucose or triacylglycerol
amino acid metabolism during fasting state
amino acids released from muscle protein
glutamine oxidised by various tissues including lymphocytes, gut and kidney
alanine and other amino acids travel to liver > carbons converted to glucose and ketone bodies, while nitrogen converted to urea and excreted out by kidneys
summary of amino acid metabolism
amino group is removed and incorporated into urea for disposal
remaining carbon skeleton broken down into CO2 and H2O or converted into glucose, acetylene CoA or ketone bodies
what is transamination
the removal of the amino group
most aminotransferases use glutamate/alpha-ketoglutarate as one of the two alpha-amino/apha-keto acid pairs involved
process used to create different amino acids the body needs by transferring amino acid groups to different keto acids > provide route for redistribution of amino acid nitrogen
which amino acids can undergo transamination
all amino acids except lysine, proline and threonine
what is the coenzyme utilised by aminotransferases
pyridoxal phosphate (PLP), derived from vitamin B6
first step of transaminases mechanism
aldehyde group of PLP forms imine (schiff base) linkage with lysine side chain on enzyme > amine nitrogen on amino acid substrate replaces enzyme lysine nitrogen in imine linkage > substrate-coenzyme stabilised by favourable hydrogen bond between PLP and imine nitrogen
second step of transaminases mechanism
abstraction of alpha-proton from PLP-amino acid adduct > immediately followed by reprotonation at aldehyde carbon of PLP > new carbon nitrogen double bond between alpha carbon and nitrogen of original amino acid > imine is hydrolysed where nitrogen is removed from amino acid to form alpha keto acid which can be degraded further > pyridoxamine phosphate (PMP) formed
what is deamination
the removal of an amino group from the amino acids as NH3
results in liberation of ammonia for urea
may be oxidative or non-oxidative
which amino acids undergo non oxidative deamination
serine, threonine, cysteine and histidine > form corresponding alpha keto acid
dehydratase catalyse deamination of serine and threonine (PLP dependent)
desulfurases responsible for deamination of cysteine (PLP dependent)
histidase catalyses deamination of histidine
what happens during oxidative deaminaiton
oxidatively removes glutamate amino group as ammonium ion to giveback alpha ketoglutarate
reaction catalysed by enzyme glutamate dehydrogenase
enzyme used NAD+ and NADP+ as coenzyme
takes place mostly in liver and kidney
definition of transdeaminase
the combined action of an transaminase and glutamate dehydrogenase
alternative pathways of deamination
L-amino acid oxidase: uses FMN as cofactor
D-amino oxidase: uses FAD as cofactor
both enzymes present in liver and kidney
both enzymes do not act on amino acids containing hydroxyl or dicarboxylic acids
how is excess ammonia from most tissues transported to liver to be excreted as urea
in tissues, glutamine synthetase uses ATP to combine glutamate with ammonium ion to form glutamine > transported to liver
in liver, glutaminase hydrolyses glutamine into glutamate with the release of the ammonium ion > urea
how is excess ammonium in muscle transported to liver
via glucose-alanine cycle
glucose converted to pyruvate via glycolysis > pyruvate interacts with glutamate to form alanine > transported to liver > converted back into pyruvate with the release of glutamate > release ammonia as urea
what is the krebs-henseleit urea cycle
responsible for detoxification of ammonia in body and synthesis of urea (takes place in liver)
step one of krebs-henseleit urea cycle
carbamoyl phosphate synthesise (CPS-I) catalyses reaction that converts ammonia from glutamate into carbamoyl phosphate > combines with ornithine to form citruline, catalysed by ornithine transcarbamoylase
occurs in mitochondria
step two of krebs-henseleit urea cycle
citrulline combines with aspartate (from Krebs cycle) to form argininosuccinate using ATP via argininosuccinate synthetase
step three of krebs-henseleit urea cycle
argininosuccinate cleaved non hydrolytically to form arginine and fumarate in elimination reaction catalysed by argininosuccinate lyase
arginine serves as precursor of urea
step four of krebs-henseleit urea cycle
guanidinium group of arginine is cleaved hydrolytically by arginase to form ornithine (recycled) and urea
how is urea cycle regulated
regulated via enzyme carbamoyl phosphate synthetase (CPS-I)
increased arginine > promotes urea cycle indirectly through NAG as it is an activator of NAG
NAG produced from acetyl coA and glutamate > when a.a catabolism increases during fasting > glutamate increases > higher NAG production > increase CPS-I activation
urea cycle disorders
hyperammonemia-I: CPS-I defective > ammonia accumulated
hyperammonemia-II: ornithine transcarbamolyase defective > ammonia accumulated
citrullinemia: argininosuccinate synthase defective: citrulline accumulated
arginosuccinic acuduria: arginase defective > arginosuccinate accumulated
argininemia: arginase defective > arginine accumulated
what are ketogenic amino acids
amino acids that form acetyl coA or acetoacetyl coA for contribution of formation of fatty acid and ketone bodies
ketogenic amino acids: isoleucine, leucine, lysine, threonine, phenylalanine, tryptophan and tyrosine
what are glucogenic amino acids
amino acids that are degraded to pyruvate and TCA cycle intermediates
some amino acids are both glucogenic and ketogenic because different parts of their carbon chains form different products
amino acids that are both ketogenic and glucogenic
threonine, tryptophan, phenylalanine, tyrosine
what are the 4 metabolic intermediates used for precursors for synthesis of non essential amino acids
pyruvate, oxaloacetate, glutamate and alpha ketoglutarate
what is reductive amination
process where glutamate is made from NH4+ and alpha ketoglutarate
nadh/nadph required
catalysed by glutamate dehydrogenase
glutamate acts as major donor of amino groups and alpha ketoglutarate acts as major acceptor of the amino groups
synthesis of serine (non essential amino acid)
OH group in 3-phosphoglycerate oxidised to keto group by 3-phosphoglycerate dehydrogenase with use of NAD+ > form 3 phosphohydroxypyruvate
undergo transmutation with glutamate to form 3-phosphoserine and alpha ketoglutarate using PLP
3-phosphoserine hydrolysed to give serine and pi
biosynthesis of glycine using serine
via reversible reaction catalysed by serine hydroxymethyltransferase
two cofactors required: prosthetic group PLP and cosubstrate tetrahydrofolate
how is cysteine synthesised from serine in plants and bacteria
by incorporation of H2S with serine providing the carbon skeleton
