Amino Acid Metabolism Flashcards
What is the major pathway to eliminate the excess of nitrogen?
Convert excess nitrogen to urea in liver ▶️ kidney (through blood) eliminated in urine
What is the major carrier of excess nitrogen from tissues?, what allows that?
Glutamine - glutamine synthetase captures excess of nitrogen aminating glutamate.
*nontoxic substance
What do the transaminases require to mediate the reaction?
Pyridoxal phosphate (PLP) derived from Vit B6
What is the other contributor of elimination excess of nitrogen in addition to liver by urea cycle?
- kidney deaminate glutamine coming from tissues ⏩ glutaminase ▶️ NH3 + H ▶️ NH4 (also act as a buffer) ▶️ urine
How do you identify a liver dysfunction vs kidney dysfunction?
- ⬆️⬆️ BUN - kidney
- ⬇️⬇️ BUN - liver
Major hallmarks in defect in the urea cycle?
- hyperammonemia, ⬆️ glutamine, ⬇️ BUN
How do you distinguish defect in urea cycle by carbamoyl-P synthetase vs ornithine transcarbamoylase deficiency?
- ⬆️ orotic acid and uracil (intermediates of pyrimidine pathway) in ornithine transcarbamoylase deficiency (orotic aciduria)
- ⬆️⬆️ carbamoyl-P ▶️ go to the pyrimidine pathway
What are the similitudes between Marfan and hemocystinemia (cystathionine synthase)?
- long fingers and toes, lens dislocation (inward and downward in cystathionine synthase, and upward and outward in Marfan)
What are the unique enzymes that use vitamin B12 as a coenzyme?
- methylmalonyl CoA mutase (adenosylcobalamin)
- N5 methyl THF homocysteine methyl transferase (methylcobalamin)
Why giving folate you can correct the megaloblastic anemia generated by Vit B12 deficiency? What condition doesn’t correct?
- ⬇️ Vit B12 ▶️ can’t use storage of THF (reduced methyl THF), can’t obtain active pool TFH. Giving it avoid that pass.
- Peripheral neuropathy
Why the deficiency of methylmalonyl CoA mutase and propionyl CoA carboxylase yield neonatal ketoacidosis?
- propionic acid pathway stops ▶️ can’t metabolize ketoacids from Val, Ile, thr, met
Symptoms of alcaptonuria
Dark urine
Ochronosis
Arthritis
Deficiency in maple syrup urine disease, and what uses that enzyme?
Branched chain ketoacid dehydrogenase
*TLCFN - thiamine, lipoic acid, CoA, FAD, NAD+
How can you differentiate deficiency of methylmalonyl CoA mutase and propionyl CoA carboxylase?
- propionyl CoA carboxylase deficiency: ⬆️⬆️ methyl citrate, hydroxypropionic acid, propionic acid
- methylmalonyl CoA mutase deficiency: ⬆️⬆️ methylmalonic acid (methylmalonic aciduria)
Why Vit B6 deficiency can lead mild homocystinemia?
- cystathionine synthase needs Vit B6 as coenzyme
Why do deficiency in Vit B12 and folate cause homocystinemia?
- function impaired of homocysteine methyl transferase N5 methyl THF B12
Most common cause of Vit B12 deficiency, and the others causes
- pernicious anemia (abs against parietal cells) ▶️ absence of intrinsic factor
- aging
- chronic pancreatitis
- long term vegetarian diet
- Infection Diphyllobothrium latum
Risk factors (causes) for folate deficiency
Pregnancy
Alcoholism
Severe malnutrition
If you find ⬇️ methionine what substance would expect to be accumulated?
- 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
What enzyme is deficiency in acute intermittent porphyria? Symptoms
- porphobilinogen deaminase
- porphobilinogen ⬆️⬆️
- abdominal pain, port wine urine, ⬆️⬆️ ALA, weakness, anxiety, paranoia, depression, paralysis, motor, sensory or autonomic neuropathy
What drug can yield an acute episode of intermittent porphyria, even any porphyria?
Barbiturates - ⬆️ synthesis cytochrome p450 ▶️ ⬆️ hem consumption ▶️ ⬇️ hem levels ▶️ ⬆️ ALA synthase activity ▶️ more porphyrin precursors
which deficiency results in porphyria that present with photo sensitivity?
- uroporphyrinogen decarboxylase ▶️ ⬆️⬆️ uroporphyrinogen-III (porphyria cutanea tarda)
Effect of lead in hem synthesis, what could be the pathology associated?
- Pb ▶️ (-) ALA dehydratase and ferrochelatase (avoid incorporation of Fe2 in heme) ▶️ microcytic sideroblastic anemia (ringed sideroblast in bone marrow)
How does isoniazid cause Sideroblastic anemia?
- isoniazid ▶️ ⬇️⬇️ Vit B6 (ALA synthase need it) ▶️ not formation Hem ▶️ iron accumulates - ringed sideroblasts in bone marrow - Sideroblastic anemia
How can you get an “acquired porphyria?
Lead poisoning ▶️ (-) ferrochelatase, Fe2+ no incorporate to porphobilinogen IX ▶️ Zn bind no enzymatic ▶️ fluorescent compound easily to identify
How can you differentiate lead poisoning anemia with Vit B6 deficiency and iron deficiency?
- Coarse basophylic stippling in RBC
How do you confirm hemolytic anemia crisis?
- ⬇️ Hb, ⬆️ Reticulocyte count
What is the level of methionine in both causes of homocystinemia?
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