Amino Acid Metabolism

Question 1

Describe the anabolic fate of AAs

Answer 1

Symthesis of
1. Non-essential amino acids
2. Biologically active peptide (heme, purine p, pyrimidine….)

Question 2

Describe catabolic fate of AAs

Answer 2

1. Ketogenic aa: lysine & leucine give acetoacetyl CoA or acetyl CoA
2. Glucogenic except 2L, produce glucose through gluconeogenesis
3. Mixed aa (phenylalanine, tyrosine, tryptophan, threonine, isoleucine) glucose & ketone body production

Question 3

Describe how the following AAs enter gluconeogensis
1. Glycine
2. Methionine

Answer 3

1. Glycine, serince -dehydratase-pyruvate, glucose
2. Methionine-transmethylation->homocysteine(react with serine), homoserine-dehydratase->a-ketobutyrate by oxidative decarboxylation ~>propionyl CoA (gluconeogenesis substrate)

Question 4

Describe fate of C-skeleton of the following:
1. Aspargine
2. Glutamine
3. Valine, isoleucine, methionine
4. Alanine
5. Serine
6. Glycine

Answer 4

1. Cleaved by asparginase into ammonia & aspartate which is converted to oxaloacetate by AST
2. Cleaved by glutaminase into ammonia & glutamate which is converted to a-ketoglutarate by transamination or through deamination by glutamate dehydrogenase
3. Converted to succinyl CoA thus are glucogenic
4. Transaminated to pyruvate (it is the major glucogenic aa)
5. Like Ala but also can be converted by serine dehydratase
6. Like Ala but can be converted to glyoxylate which can be oxidised to oxalate or transaminate to glycine. Also it can be cleaved into methylene-THF, CO2 & NH3 by glycine cleavage system

Question 5

List the essential aa

Answer 5

Lysine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, threonine

Question 6

Describe the biological imp of methionine

Answer 6

Met & Cys are major sources of sulfur in the body, it is essential & glucogenic amino acids
Imp for Synthesis of S-adenosyl methionine which is the major methyl-group donor. Methionine reacts with ATP forming SAM. After donation it forms SAH which is hydrolysed to homocysteine & adenosine.
Reactions requiring transmethylation:
Synthesis of creatine, choline from serine, melatonin from serotonin, epinepherine from NE & catabolism of CAs

Question 7

Describe the fates of homocysteine

Answer 7

1. Resynthesis of methionine: in case of Met def homocysteine accepts a methyl group from N5-methyl-THF in a methylcobalamin-requiring reaction forming Met
2. Syntheisis of cysteine if adequate stores of methionine are present

Question 8

Compare type 1 & 2 homocystinuria with respect cause & serum level of met

Answer 8

Type 1: cystathionine synthase/vit B6 def. Serum Met level is increased
Type 2: def of homocysteine methyl transferase, folic acid, THF reductase, B12. Serum Met is dec

Question 9

Describe C/P of homocytinuria

Answer 9

Homocysteine binds lysine of collagen, preventing cross-linking so weak ECM is present, resulting in:
1. Mental retardation
2. Cataracts, dislocation of lens, retinal detachment
3. Bone deformities
4. Vascular disease, athersclerosis
5. Accumulation of homocysteine in serum & inc excretion in urine

Question 10

How does homocysteine elevation cause atherogenesis

Answer 10

Homocysteine forms homocysteine thiolactone (free radical) , which thiolates LDL. These modified particles tend to aggregate & are endocytosed by macrophages increasing tendency for atherogenesis and intravascular thrombosis.

Question 11

Describe treatment of types of homocysteinuria

Answer 11

Type 1: dec methionine in diet, provide B6 & cysteine, choline supplementation as B6 is imp for its synthesis
Type 2: folic acid/vit B12 supplements

Question 12

Mode of inheritance of primary hyperoxaluria is……

Answer 12

Autosomal recessive

Question 13

Describe the pathogenesis of 1ry hyperoxaluria

Answer 13

Due to transaminase deficiency that converts glyoxylate to glycine. Thus glyoxylate accumulates & oxidized to oxalate, which will precipitate in presence of Ca & causes formation of oxalate stones & kidney damage. Build up of oxalate in body results in renal & bladder stones. Stones cause urinary obstruction, 2ry infection of urine & eventually kidney damage.

Question 14

What is the cause of alkaptonuria?

Answer 14

Due to accumulation of homogentisic acid, an intermediate of tyrosine metabolism due to def of homogentisate oxidase.

Question 15

List symptoms of alkaptonuria

Answer 15

1. Homogentisic aciduria
2. Later there is Chronic accumulation of this pigment in cartilage may cause arthritic joint pain with black ochronotic pigmentation of cartilage & collagenous tissue.

Question 16

Treatment of alkaptonuria

Answer 16

Low protein diet esp phenylalanine & tyrosine to reduce level of homogentisic acid & dec amount of pigment deposited in the body. It is not life-threatining but can be crippling.