Amino Acid Metabolism

Question 1

What is the major pathway to eliminate the excess of nitrogen?

Answer 1

Convert excess nitrogen to urea in liver ▶️ kidney (through blood) eliminated in urine

Question 2

What is the major carrier of excess nitrogen from tissues?, what allows that?

Answer 2

Glutamine - glutamine synthetase captures excess of nitrogen aminating glutamate.
*nontoxic substance

Question 3

What do the transaminases require to mediate the reaction?

Answer 3

Pyridoxal phosphate (PLP) derived from Vit B6

Question 4

What is the other contributor of elimination excess of nitrogen in addition to liver by urea cycle?

Answer 4

• kidney deaminate glutamine coming from tissues ⏩ glutaminase ▶️ NH3 + H ▶️ NH4 (also act as a buffer) ▶️ urine

Question 5

How do you identify a liver dysfunction vs kidney dysfunction?

Answer 5

• ⬆️⬆️ BUN - kidney

- ⬇️⬇️ BUN - liver

Question 6

Major hallmarks in defect in the urea cycle?

Answer 6

• hyperammonemia, ⬆️ glutamine, ⬇️ BUN

Question 7

How do you distinguish defect in urea cycle by carbamoyl-P synthetase vs ornithine transcarbamoylase deficiency?

Answer 7

• ⬆️ orotic acid and uracil (intermediates of pyrimidine pathway) in ornithine transcarbamoylase deficiency (orotic aciduria)
• ⬆️⬆️ carbamoyl-P ▶️ go to the pyrimidine pathway

Question 8

What are the similitudes between Marfan and hemocystinemia (cystathionine synthase)?

Answer 8

• long fingers and toes, lens dislocation (inward and downward in cystathionine synthase, and upward and outward in Marfan)

Question 9

What are the unique enzymes that use vitamin B12 as a coenzyme?

Answer 9

• methylmalonyl CoA mutase (adenosylcobalamin)

- N5 methyl THF homocysteine methyl transferase (methylcobalamin)

Question 10

Why giving folate you can correct the megaloblastic anemia generated by Vit B12 deficiency? What condition doesn’t correct?

Answer 10

• ⬇️ Vit B12 ▶️ can’t use storage of THF (reduced methyl THF), can’t obtain active pool TFH. Giving it avoid that pass.
• Peripheral neuropathy

Question 11

Why the deficiency of methylmalonyl CoA mutase and propionyl CoA carboxylase yield neonatal ketoacidosis?

Answer 11

• propionic acid pathway stops ▶️ can’t metabolize ketoacids from Val, Ile, thr, met

Question 12

Symptoms of alcaptonuria

Answer 12

Dark urine
Ochronosis
Arthritis

Question 13

Deficiency in maple syrup urine disease, and what uses that enzyme?

Answer 13

Branched chain ketoacid dehydrogenase

*TLCFN - thiamine, lipoic acid, CoA, FAD, NAD+

Question 14

How can you differentiate deficiency of methylmalonyl CoA mutase and propionyl CoA carboxylase?

Answer 14

• propionyl CoA carboxylase deficiency: ⬆️⬆️ methyl citrate, hydroxypropionic acid, propionic acid
• methylmalonyl CoA mutase deficiency: ⬆️⬆️ methylmalonic acid (methylmalonic aciduria)

Question 15

Why Vit B6 deficiency can lead mild homocystinemia?

Answer 15

• cystathionine synthase needs Vit B6 as coenzyme

Question 16

Why do deficiency in Vit B12 and folate cause homocystinemia?

Answer 16

• function impaired of homocysteine methyl transferase N5 methyl THF B12

Question 17

Most common cause of Vit B12 deficiency, and the others causes

Answer 17

1. pernicious anemia (abs against parietal cells) ▶️ absence of intrinsic factor
   - aging
   - chronic pancreatitis
   - long term vegetarian diet
   - Infection Diphyllobothrium latum

Question 18

Risk factors (causes) for folate deficiency

Answer 18

Pregnancy
Alcoholism
Severe malnutrition

Question 19

If you find ⬇️ methionine what substance would expect to be accumulated?

Answer 19

• methylmalonic acid (methylmalonic aciduria)
• methylmalonyl CoA mutase can’t work properly without B12, suspect that deficiency with ⬇️ met ▶️ def B12 can’t covert homocysteine to met

Question 20

What enzyme is deficiency in acute intermittent porphyria? Symptoms

Answer 20

• porphobilinogen deaminase
• porphobilinogen ⬆️⬆️
• abdominal pain, port wine urine, ⬆️⬆️ ALA, weakness, anxiety, paranoia, depression, paralysis, motor, sensory or autonomic neuropathy

Question 21

What drug can yield an acute episode of intermittent porphyria, even any porphyria?

Answer 21

Barbiturates - ⬆️ synthesis cytochrome p450 ▶️ ⬆️ hem consumption ▶️ ⬇️ hem levels ▶️ ⬆️ ALA synthase activity ▶️ more porphyrin precursors

Question 22

which deficiency results in porphyria that present with photo sensitivity?

Answer 22

• uroporphyrinogen decarboxylase ▶️ ⬆️⬆️ uroporphyrinogen-III (porphyria cutanea tarda)

Question 23

Effect of lead in hem synthesis, what could be the pathology associated?

Answer 23

• Pb ▶️ (-) ALA dehydratase and ferrochelatase (avoid incorporation of Fe2 in heme) ▶️ microcytic sideroblastic anemia (ringed sideroblast in bone marrow)

Question 24

How does isoniazid cause Sideroblastic anemia?

Answer 24

• isoniazid ▶️ ⬇️⬇️ Vit B6 (ALA synthase need it) ▶️ not formation Hem ▶️ iron accumulates - ringed sideroblasts in bone marrow - Sideroblastic anemia

Question 25

How can you get an “acquired porphyria?

Answer 25

Lead poisoning ▶️ (-) ferrochelatase, Fe2+ no incorporate to porphobilinogen IX ▶️ Zn bind no enzymatic ▶️ fluorescent compound easily to identify

Question 26

How can you differentiate lead poisoning anemia with Vit B6 deficiency and iron deficiency?

Answer 26

• Coarse basophylic stippling in RBC

Question 27

How do you confirm hemolytic anemia crisis?

Answer 27

• ⬇️ Hb, ⬆️ Reticulocyte count

Question 28

What is the level of methionine in both causes of homocystinemia?

Answer 28

.