30-31: AMINO ACID METABOLISM

Question 1

amino acid degradation

Answer 1

• excess AAs can’t be stored; degraded; used as fuel to provide energy or biosynthetic intermediates
• @-amino group is removed; most N is excreted as urea
• carbon skeleton broken down into TCA cycle intermediates (7)
• all 20 AAs feed into TCA
• glucogenic AAs: broken down to oxaloacetate, pyruvate, a-ketoglu, succinyl coa, fumarate can be converted to glucose via phosphoenolpyruvate then gluconeogenesis
• ketogenic AAs: broken down to acetyl coa; cannot be used to synthesise glucose (lys, leu); can be used to make ketone bodies
• both: broken down to more than one component; parts of can be converted to glu (phe, tyr tryp, isoleu)

Question 2

why need to remove amino acids?

Answer 2

• due to genetic disorders
• if not treated, can get serious brain damage
• AAs toxic if they build up in the body

e.g phenylketonuria- defect in enzyme that converts Phe to Tyr (quite common); easy to treat; control diet for low Phe

Question 3

transamination - removal of @-amino group

Answer 3

-transfer of amino group to a-keto acid
-catalysed by aminotransferases/transaminases using PLP as cofactor (pyridoxine B6)
-collect NH3 groups from all 20 AAs to form glutamate
-e.g. Asp + a-ketoglu = oxaloacetate + glutamate
Ala + a-ketoglu = pyruvate + glutamate
-completely reversible; operate at eq; direction depends on concentration of reactants in cell

Question 4

glutamate dehydrogenase reaction

Answer 4

-oxidative deamination reaction
1. oxidation to give schiff base intermediate (use NAD/P)
2. hydrolysis releases ammonia; forms a-ketoglu
-in mammals, glu DH is in mit.matrix (ammonia to urea in urea cycle drives reaction forwards)
-

Question 5

urea cycle

Answer 5

-starts in mit.matrix; rest in cytosol

1. ammonia + bicarbonate = “carbamoyl phosphate” (activated donor of carbamoyl group); uses 2ATP; cat by “” synthetase I
2. transfer carbamoyl group to ornithine = citrulline; cat by ornithine transcarbamoylase
3. 2nd N from urea comes from Asp; condensation bet amino group of Asp and carbonyl of citrulline = arginosuccinate; cat by arginosuccinate synthetase; hydrolysis ATP to AMP+Ppi
4. cleavage; release fumarate and make arginine; by arginosuccinase
5. water comes in and breaks off 2N as urea; hydrolysis by arginase; excrete urea and recreate ornithine

-to get rid of 2N need equivalent of 4ATP; essential cycle

Question 6

control entry of nitrogen into urea cycle

Answer 6

-1st reaction cat by carbamoyl phosphate synthetase I

1. bicarbonate phosphorylated; hydrolyse ATP
2. P group displaced by ammonia
3. phosphorylate carbamate to give carbamoyl phosphate

uses 2ATP

Question 7

link of urea to TCA cycle

Answer 7

-linked by fumarate; produced when you cleave arginosuccinate to make arginine

Question 8

where to get Asp from?

Answer 8

-transamination of oxaloacetate using glutamate as N-donor; cat by asp aminotransferase; produces a-ketoglu

Question 9

amino acid synthesis

Answer 9

• can all be synthesised from common precursors of TCA cycle/ glycolysis/pentose-P-pathway
• essential AAs must be obtained from diet (e.g. plants); PVT TIM HALL
• phenylalanine hydroxylation to tyrosine
• ribose-5-P to histidine by phosphoribosyl pyrophosphate

Question 10

nitrogen metabolism

Answer 10

-role of glutamine
don’t want to excrete all (ammonia) NH4+ as urea; some needed for synthesis e.g. nucleotides, amino sugars, other AAs
-some ammonia incorporated in glutamine; acts as non-toxic carrier of N; can be used as N donor
-reaction cat by glutamine synthase