amino acids

Question 1

why does the body need amino acids? (6)

Answer 1

1. protein synthesis
2. Energy and gluconeogenic substrates
3. Neurotransmitters
4. Non-peptide hormones eg. thyroxine, epinephrine.
5. Heme biosynthesis.
6. Nucleotide biosynthesis.

Question 2

what are the sources of amino acids in the body? (3)

Answer 2

1. dietary proteins (exogenous, MAIN)
2. breakdown of body’s own proteins (endogenous)
3. biosynthesis

Question 3

what are aminoacidurias?

Answer 3

• high amount of amino acid in urine
• due to:
  1. defective amino-acid transport through renal (reabsorption)
  2. defective small intestinal epithelia (absorption)

Question 4

what is cystinuria?

Answer 4

• failure in reabsorption and uptake of cystine, ornithine, arginine, lysine (COAL)
• may cause cystine kidney stones

Question 5

what is hartnup’s disease?

Answer 5

• 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)

Question 6

how are amino acids lost by the body (4)?

Answer 6

1. use in protein synthesis (e.g. enzyme, peptide hormones)
2. non-protein body constituents (nucleic acids, creatine, etc)
3. metabolism for energy or conversion of fat to carbs
4. small loss in urine or sweat

Question 7

what happens to excess amino acids?

Answer 7

used as metabolic fuel (stored as glucose or ketones)

Question 8

how are amino acids converted to keto acids? (3)

Answer 8

1. oxidative deamination (main)
2. transamination
3. non-oxidative deamination

Question 9

what is the process of oxidative deamination?

Answer 9

L-glutamate→ (below)→ alpha-Keto Glutarate

1. enzyme: L-Glutamate-dehydrogenase, GDH
2. NAD+/NADP+→ NADH/NADPH (oxidative)
3. H2O→ NH4+ (deamination)

Question 10

describe the process of transamination

Answer 10

transfer of amino group from amino acid (e.g. aspartate) to ketoacid (a-KG)→ ketoacid (e.g. oxaloacetate) and amino acid (glutamate)

Question 11

describe the process of aspartate transamination

Answer 11

aspartate + aKG ↔ (AST)↔ oxaloacetate + glutamate

Question 12

describe the process of alanine transamination

Answer 12

alanine + aKG ↔ (ALT) ↔ pyruvate + glutamate

Question 13

how can NH4+ be obtained from transamination?

Answer 13

link to deamination!!
1. transamination: AA + aKG → KA + glutamate
2. oxidative deamination: glutamate + NAD+ + H2O→[GDH]→ a-KG + NADH + H+ + NH4+

Question 14

what is the importance of transamination? (2)

Answer 14

1. funnels amino grp fr amino acids to form glutamate to convert into ammonia (via oxidative deamination)
2. synthesis of non-essential amino acids

Question 15

how are ALT & AST used as diagnostic tools?

Answer 15

• 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

Question 16

how is ammonia excreted?

Answer 16

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+)

Question 17

how is NH4+ trapped for excretion?

Answer 17

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

Question 18

what determines the direction of GDH in oxidative deamination?

Answer 18

NH4+ + aKG→ glutamate
GDH stimulated by HIGH energy: ATP & GTP

glutamate→ aKG + NH4+
GDH stimulated by LOW energy: ADP & GDP
ETC

Question 19

why is NH4+ accumulation toxic?

Answer 19

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

Question 20

what are the functions of glutamate? (3)

Answer 20

synthesized from a-KG (via oxidative deamination)

1. synthesize non-essential amino acids (via transamination)
2. synthesize glutathione
3. synthesize GABA in the brain (neurotransmitter)

Question 21

what are the functions of glutamine (4)

Answer 21

synthesized from glutamate (using glutamine synthetase)

1. catabolizes to glutamate (via glutaminase)
2. allows transamination of fructose-6-phosphate to glucosamine-6-P
3. synthesizes purines & pyrimidines (from amide N of glutamine)
4. nucleotide metabolism

Question 22

what is the metabolism of aspartate? (4)

Answer 22

1. synthesized by transamination from oxaloacetate + glutamate→ aspartate + aKG
2. synthesized from asparagine→(asparaginase)→ aspartate + NH4+)
3. synthesizes asparagine via asparagine synthetase
4. synthesizes purines & pyrimidines (gets incorporated)

Question 23

what enzymes are defective in phenylketonuria?(2)

Answer 23

1. phenylalanine hydroxylase
2. tetrahydropteridine reductase

Question 24

what enzyme is defective in tyrosinemia type 1/tyrosinosis?

Answer 24

fumarylacetoacetate hydroxylase

Question 25

what enzyme is defective in tyrosinemia type 2

Answer 25

tyrosine transaminase