W10 Amino Acid Metabolism

Question 1

primary function of amino acids

Answer 1

act as monomer unit in protein synthesis

used as substrate for biosynthesis reactions for nitric oxide, hormones (nicotinamide), heme, purine and pyrimidine bases

Question 2

how does the body obtain amino acids

Answer 2

amino acids cannot be stored in the body

either by:
- dietary intake
- amino acid synthesis
- degradation of pre-existing proteins

Question 3

amino acid metabolism in fed state

Answer 3

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

Question 4

amino acid metabolism during fasting state

Answer 4

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

Question 5

summary of amino acid metabolism

Answer 5

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

Question 6

what is transamination

Answer 6

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

Question 7

which amino acids can undergo transamination

Answer 7

all amino acids except lysine, proline and threonine

Question 8

what is the coenzyme utilised by aminotransferases

Answer 8

pyridoxal phosphate (PLP), derived from vitamin B6

Question 9

first step of transaminases mechanism

Answer 9

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

Question 10

second step of transaminases mechanism

Answer 10

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

Question 11

what is deamination

Answer 11

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

Question 12

which amino acids undergo non oxidative deamination

Answer 12

serine, threonine, cysteine and histidine > form corresponding alpha keto acid

dehydratase catalyse deamination of serine and throning (PLP dependent)

desulfurases responsible for deamination of cysteine (PLP dependent)

histidase catalyses deamination of histidine

Question 13

what happens during oxidative deaminaiton

Answer 13

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

Question 14

definition of transdeaminase

Answer 14

the combined action of an transaminase and glutamate dehydrogenase

Question 15

alternative pathways of deamination

Answer 15

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

Question 16

how is excess ammonia from most tissues transported to liver to be excreted as urea

Answer 16

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

Question 17

how is excess ammonium in muscle transported to liver

Answer 17

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

Question 18

what is the krebs-henseleit urea cycle

Answer 18

responsible for detoxification of ammonia in body and synthesis of urea (takes place in liver)

Question 19

step one of krebs-henseleit urea cycle

Answer 19

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

Question 20

step two of krebs-henseleit urea cycle

Answer 20

citrulline combines with aspartate (from Krebs cycle) to form argininosuccinate using ATP via argininosuccinate synthetase

Question 21

step three of krebs-henseleit urea cycle

Answer 21

argininosuccinate cleaved non hydrolytic ally to form arginine and fumarate in elimination reaction catalysed by argininosuccinate lyase

arginine serves as precursor of urea

Question 22

step four of krebs-henseleit urea cycle

Answer 22

guanidinium group of arginine is cleaved hydrolytically by arginase to form ornithine (recycled) and urea

Question 23

how is urea cycle regulated

Answer 23

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

Question 24

urea cycle disorders

Answer 24

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

Question 25

what are ketogenic amino acids

Answer 25

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

Question 26

what are glucogenic amino acids

Answer 26

amino acids that are degraded other than pyruvate or TCA intermediates

some amino acids are both glucogenic and ketogenic because different parts of their carbon chains form different products

Question 27

amino acids that are both ketogenic and glucogenic

Answer 27

threonine, tryptophan, phenylalanine, tyrosine

Question 28

what are the 4 metabolic intermediates used for precursors for synthesis of non essential amino acids

Answer 28

pyruvate, oxaloacetate, glutamate and alpha ketoglutarate

Question 29

what is reductive amination

Answer 29

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

Question 30

synthesis of serine (non essential amino acid)

Answer 30

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

Question 31

biosynthesis of glycine using serine

Answer 31

via reversible reaction catalysed by serine hydroxymethyltransferase

two cofactors required: prosthetic group PLP and cosubstrate tetrahydrofolate

Question 32

how is cysteine synthesised from serine in plants and bacteria

Answer 32

by incorporation of H2S with serine providing the carbon skeleton