SYLLABUS 20: Amino Acid Catabolism Flashcards Preview

MCG > SYLLABUS 20: Amino Acid Catabolism > Flashcards

Flashcards in SYLLABUS 20: Amino Acid Catabolism Deck (50):

when does amino acid catabolism occur?

when aa are in excess, in positive nitrogen balance, and you're taking in more protein than need to replace body protein or make compounds 

once body has enough aa to synthesize new protein & make nitrogenous molecules, start breaking down excess aa in diet 



how are aa removed from the body

only via break down to other products, as there's no storage form of aa 


what tissues degrade excess aa?

all tissues, but especially liver and muscle


what do aa break down become?

C products: 

acetyl CoA 



TCA cycle intermediates- OAA, aKG, succinyl CoA, fumarate

amino groups become urea 


what are glucogeninc aa?

amino acids that produce pyruvate or any of the 4 TCA cycle intermediates, OAA, succinyl CoA, fumarate, aKG 

aka aa that break down to anything else 

includes all aa except for leucine, and to a large extent lysine


what are ketogenic aa?

aas that produce acetyl CoA and acetoacetate 

leucine, lysine, phenylalanine, tyrosine, isoleucine, tryptophan 



which aa are both glucogenic and ketogenic?

phenylalanine, tyrosine, isoleucine, tryptophan 

b/c when break down, produce either pyruvate or a TCA cycle intermediate as well as acetyl CoA or acetoacetate 


what are the C3  family of aa? what do they break down to?

alanine, serine, glycine, cysteine, tryptophan 

break down to pyruvate 


how does alanine break down

becomes pyruvate via GPT transamination rxn: 

Ala + aKG -> Pyr + GLUT 


how does tryptophan break down

its side chain is released as alanine during break down 


how does cysteine break down? 

bio importances of this?

cysteine loses its SH group, eventually forming sulfate + pyruvate 

sulfate is important in:

1. biochemical conjugation reactions w/ drugs 

2. in interacting w/ estrogens (estradiol sufate)

3. formation of cell surface and joint biochemicals such as chondroitin and hyaluronic acid sulfates  


how does glycine break down?

becomes serine via serine transhydroxymethylase rxn, and Ser -> Pyruvate 


how does serine break down?

serine can be dehydrated to pyruvate by serine dehydratase 


what are the C4 family of aa?

aspartate and asparagine 



how is aspartate broken down?

Aspartate -> OAA via GOT transaminase reaction


how is asparagine broken down?

Asparagine -> aspartate + ammonia by asparaginase 



usefulness of asparaginase?

besides breaking down asparagine -> ammonia + aspartate, used to treat some leukemias beacuse asparagine is the AA in lowest level in proteins, so if remove asparagine with asparaginase and hydrolyze it to aspartate, can deplete tumor cell of asparagine and stop it from rapidly growing and dividing


what aa are in the C5 family? what do they make?

glutamate, glutamine, histidine, proline, arginine 

all metabolized to aKG 


how are the c5 family aa broken down?

glutamine, histidine, proline, arginine are all converted to glutamate 

glutamate is oxidized to aKG by glutamate DH reaction 


how does glutamine get metabolized

glutamine is hydrolyzed to glutamate + NH3 by glutaminase 



how is histidine metabolized

histidine's metabolized to N-formimino glutamic acid 

formimino group is transferred to THF to produce N-formimino THF + glutamate

N-Formiminot THF is major source of C for foic acid pool 


how is arginine metabolized

arginine is hydrolyzed to ornithine + urea by arinase 

ornithine can produce glutamic semi-aldehyde, which -> glutamate


what aa make succinyl CoA?

Met, Val, Thr, Isol which -> propionyl CoA -> methylmalonyl CoA -> succinyl CoA 


what happens to the succinyl CoA made from the succinyl CoA family of aa?

breaks down to propionyl CoA 

propionyl CoA -> D methylmalonyl -> L methylmalonyl -> succinyl CoA via methylmalonyl CoA mutase rxn 



what causes methylmalonyl aciduria?

inborn error of metabolism causing deficiency of the methylmalonyl CoA mutase or of B12 or of the deoxyadenosyl transferase 


what are the branched chain aa? 

what happens to them in their breakdown?

valine, isoleucine, leucine 

1. transamination, which converts the aa to the respective alpha keto acid of that particular amino acid 

2. alpha keto acid undergoes oxidative decarboxylation to produce CO2 and acyl CoA product 

this is catalyzed by acyl CoA DH complex

DH complex uses CoA, NAD, FAD, lipoic acid 

3. acyl COA is further metabolized 

acyl CoA from valine or isoleucine -> propionyl CoA -> methylmalonyl COA 

acyl CoA from leucine -> acetyl CoA & acetoacetate


what's acetoacetate's categorization?

ketogenic because becomes acetoacetate and acetyl CoA, ultimately 


what causes maple syrup urine disease? 

what happens as result?

deficiency of branch chain a-keto acid DH needed for breakdown of Val, Iso, Leu 

causes accumulation of these aa (Valine, Isoleucine, Leucine), and of the alpha keto acids produced by the transamination reaction 

these are toxic compounds to the developing nervous system and cause severe neuro disturbances, failure to thrive, coma, death w/in first 2 years of life 


how to treat maple syrup urine disease?

limit branch chain aa in diet, easy b/c these are all essential aa



how does maple syrup urine disease get its name?

urine spells like maple syrupe when a-keto acids spill over into the urine 


how is phenylalanine metabolized?

phenylalanine -> tyrosine by phenylalanine hydroxylase 

this uses oxygen and THB as cofactor 

this is a mixed function oxidation 

THB is oxidized to DHB


function of THB in phenylalanine catabolism?

supplies the reducing equivalents to form the OH of tyrosine and water 

it becomes oxidized to DHB



how is cofactor regenerated for phenylalanine catabolism?

THB is regenerated from DHB by NADPH + DHB reductase 



what is a mixed function oxidation? when does it occur?

in phenylalanine -> tyrosine by phenylalanine hydroxylase, which uses oxygen and THB as cofactor, the 2 atoms of O go to different products:

1 atom of O from O2 is incorporated into tyrosine product 

1 atom of O from O2 is incorporated into water 



is Phe an essential aa? is Tyr?

Phe is essential 

Tyr is non-essential, as it can be made from Phe 


what causes phenylketonuria?

inborn error of metabolism caused by deficiency of phenylalanine hydroxylase, which converts phenylalanine -> tyrosine and in some rarer cases, deficiency of THB, the cofactor 

phenylalanine thus accumulates, -> side pathways, produces phenylketones: phenylpyruvate, pheynacetate, and phenyllactate 

these cause severe neurological disturbances, mental retardation, death by age 20-30 if not treated


incidience of phenylketonuria?



how can you treat PKU? what aa would you add to a diet developed to treat PKU? 

limit phenylalanine intake 

supplement tyrosine intake 


how does tyrosine catabolism proceed?

tyrosine itself or tyrosine from phenylalanine -> fumarate and acetoacetate by this pathway: 

1. tyrosine undergoes transamination, produces para-hydroxyphenylpyruvate 

2. p-hydroxyphenylpyruvate -> homogentisic acid by p-hydroxyphenylpyruate hydroxylase, which require sVitamin C (ascorbic Acid) 

this step is an oxidation, hydroxylation, decarboxylation and ring migration! 

3. homogentisic acid oxidized to fumarylacetoacetate by homogentisic acid oxidase 


how are tyrosine and phenylalanine both ketogenic and glucogenic?

phenylalanine -> tyrosine 

and tyrosine -> fumarate, which is TCA cycle = glucogenic, and acetoacetate, which is ketone body = ketogenic


what causes alcaptonuria? how does it manfest?

deficiency in the enzyme homogentisic acid oxidase which oxidizes homogentisic acid to fumarylacetoacetate 

homogentisic acid is excreted into the urine, which becomes black as homogentisic acid gets further oxidized 

not severe disease, but assoc w/ severe arthritis


treatment for alcaptonuria?

decrease phenylalanine and tyrosine intake


how does tryptophan metabolism proceed?

broken to alanine, acetyl CoA, and ammonia 

thus it's both ketogenic and glucogenic 


why are phenylalanine or isoleucine considered both glucogenic and ketogenic aa? 

because they can form both glucogenic and ketone body intermediates.

Phenylalanine -> fumarate which is a TCA cycle intermediate which -> gluconeogenesis, and

isoleucine -> propionyl CoA -> L/D methylmalonyl CoA -> succinyl CoA -> gluconeogenesis,

however phenylalanine also -> acetoacetate, which is a ketone body, and

isoleucine -> acetyl CoA which + acetoacetyal CoA -> HMG CoA -> acetoacetate. 


why can't leuceine be used for glugoneogenesis? 

because it is catabolized to HmG CoA which is a ketone body intermediate that becomes acetoacetate; it’s not broken down to an intermediate i.e. from the TCA cycle that can undergo gluconeogenesis


how would carbon atoms from an aa like alanine wind up in a newly synthesized FA like palmitate? 

Carbon atoms from an aa like alanine could become part of a FA like palmitate because alanine -> pyruvate via GPT transamination reaction, and pyruvate -> acetyl CoA -> malonyl CoA ->->-> FA synthesis pathway -> palmitic acid


what are causes for PKU? how is it treated? 

PKU is caused by a deficiency in phenylalanine hydroxylase, which converts phenylalanine -> tyrosine; this causes phenylalanine to accumulate and undergo side pathway reactions to phenylketones: phenylpyruvate, phenylacetate, and phenyllactate.

Presence of these compounds causes severe neurological disturbances, mental retardation, and death by age 20-30 if not treated.

This is treatable by restriction of phenylalanine in the diet, while supplementing tyrosine since tyrosine is a metabolic product of phenylalanine catabolism


what are casues for MSUD, how is it treated? 

Maple Syrup Urine Disease is caused by deficiency of a branch chain a-keto acid DH needed for the breakdown of Val, Iso, or Leu.

This causes accumulation of Val, Iso, or Leu, and of a-keto acids produced by the transamination reactions they undergo.

These acids are toxic compounds to the developing nervous system and cause severe neurological disturbances, failure to thrive, coma, and death within the first 2 years of life.

This is treatable by limiting brach chain amino acid in the diet. 


what is a mixed function oxidase?

is a reaction that uses O2, and splits the atoms of O to put each in a different product of the reaction.

In aa catabolism, this occurs with phenylalanine -> tyrosine by phenylalanine hydroxylase, in which 1 atom of O is incorporated into the tyrosine product and 1 atom of O is incorporated into water


what is alkaptonuria?

caused by a deficiency in homogentisic acid oxidase, which oxidizes homogentisic acid to fumarylacetoacetate.

Homogentisic acid’s excreted into the urine, and thus further oxidized, turning urine black

Decks in MCG Class (77):