amino acids Flashcards
why does the body need amino acids? (6)
- protein synthesis
- Energy and gluconeogenic substrates
- Neurotransmitters
- Non-peptide hormones eg. thyroxine, epinephrine.
- Heme biosynthesis.
- Nucleotide biosynthesis.
what are the sources of amino acids in the body? (3)
- dietary proteins (exogenous, MAIN)
- breakdown of body’s own proteins (endogenous)
- biosynthesis
what are aminoacidurias?
- high amount of amino acid in urine
- due to:
1. defective amino-acid transport through renal (reabsorption)
2. defective small intestinal epithelia (absorption)
what is cystinuria?
- failure in reabsorption and uptake of cystine, ornithine, arginine, lysine (COAL)
- may cause cystine kidney stones
what is hartnup’s disease?
- failure in the reabsorption and uptake of trp, phe and other neutral amino acids.
symptoms:
- Cerebellar ataxia (lack of coordination of involuntary movement)
- Pellagra-like symptoms eg. skin lesions, dermatitis (nicotinic acid/nicotinamide deficiency)
how are amino acids lost by the body (4)?
- use in protein synthesis (e.g. enzyme, peptide hormones)
- non-protein body constituents (nucleic acids, creatine, etc)
- metabolism for energy or conversion of fat to carbs
- small loss in urine or sweat
what happens to excess amino acids?
used as metabolic fuel (stored as glucose or ketones)
how are amino acids converted to keto acids? (3)
- oxidative deamination (main)
- transamination
- non-oxidative deamination
what is the process of oxidative deamination?
L-glutamate→ (below)→ alpha-Keto Glutarate
- enzyme: L-Glutamate-dehydrogenase, GDH
- NAD+/NADP+→ NADH/NADPH (oxidative)
- H2O→ NH4+ (deamination)
describe the process of transamination
transfer of amino group from amino acid (e.g. aspartate) to ketoacid (a-KG)→ ketoacid (e.g. oxaloacetate) and amino acid (glutamate)
describe the process of aspartate transamination
aspartate + aKG ↔ (AST)↔ oxaloacetate + glutamate
describe the process of alanine transamination
alanine + aKG ↔ (ALT) ↔ pyruvate + glutamate
how can NH4+ be obtained from transamination?
link to deamination!!
1. transamination: AA + aKG → KA + glutamate
2. oxidative deamination: glutamate + NAD+ + H2O→[GDH]→ a-KG + NADH + H+ + NH4+
what is the importance of transamination? (2)
- funnels amino grp fr amino acids to form glutamate to convert into ammonia (via oxidative deamination)
- synthesis of non-essential amino acids
how are ALT & AST used as diagnostic tools?
- ALT primarily found in the liver, AST found in various tissues (e.g. liver, heart, muscles, brain etc)
- intracellular AST & ALT are released into blood when cells are damaged
- raised ALT→ liver damage/inflammation
- raised AST→ necrosis of disease of liver/other tissues
how is ammonia excreted?
CARRY AMMONIA
1. reversal of oxidative deamination by GDH (NH4+ + a-KG→ glutamate)
2. glutamine synthesis by glutamine synthetase (glutamate + NH4+→ L-glutamine)
EXCRETE AMMONIA (reverse)
3. glutamate regeneration by glutaminase (glutamine→ glutamate + NH4+)
4. oxidative deamination by GDH (glutamate→ aKG + NH4+)
how is NH4+ trapped for excretion?
pKa of NH4+ is 9.3
hence at body’s pH of 7.4, ~99% of ammonia will be NH4+→ ion cannot cross cell membranes→ ion trapping
what determines the direction of GDH in oxidative deamination?
NH4+ + aKG→ glutamate
GDH stimulated by HIGH energy: ATP & GTP
glutamate→ aKG + NH4+
GDH stimulated by LOW energy: ADP & GDP
ETC
why is NH4+ accumulation toxic?
refer to oxidative deamination:
Glutamate ↔ a-KG + NH4+
fwd: NADH/NADPH
bwd: NAD+/NADP+
when NH4+ accumulates, backward reaction is favoured, NADH/NADPH and aKG falls→ toxicity
what are the functions of glutamate? (3)
synthesized from a-KG (via oxidative deamination)
- synthesize non-essential amino acids (via transamination)
- synthesize glutathione
- synthesize GABA in the brain (neurotransmitter)
what are the functions of glutamine (4)
synthesized from glutamate (using glutamine synthetase)
- catabolizes to glutamate (via glutaminase)
- allows transamination of fructose-6-phosphate to glucosamine-6-P
- synthesizes purines & pyrimidines (from amide N of glutamine)
- nucleotide metabolism
what is the metabolism of aspartate? (4)
- synthesized by transamination from oxaloacetate + glutamate→ aspartate + aKG
- synthesized from asparagine→(asparaginase)→ aspartate + NH4+)
- synthesizes asparagine via asparagine synthetase
- synthesizes purines & pyrimidines (gets incorporated)
what enzymes are defective in phenylketonuria?(2)
- phenylalanine hydroxylase
- tetrahydropteridine reductase
what enzyme is defective in tyrosinemia type 1/tyrosinosis?
fumarylacetoacetate hydroxylase
