Biochemistry (cofactors and deficiencies) Flashcards
What is biotin (B7) a cofactor for?
several carboxylase reactions including pyruvate carboxylase (pyruvate to oxaloacetate), acetyl-CoA carboxylase (acetyl-CoA to malonyl CoA), and propionyl-CoA carboxylase (propionyl-CoA to methylmalonyl CoA)
What enzyme is B6 a cofactor for? What does the enzyme do?
Alanine transaminase. Catalzyes the reversible reaction from pyruvate and glutamate to alanine and alpha-ketoglutarate.
Heme is broken down to biliverdin by what enzyme?
Biliverdin is broken down into unconjugated bilirubin by what enzyme?
Heme –> biliverdin = heme oxygenase
biliverdin –> unconjugated bili = biliverdin reductase
Tyrosinase deficiency causes what disorder?
Albinism. This is because this enzyme functions in the pathway of melanin production from DOPA or tyrosine as a substrate.
What enzyme does carbidopa inhibit and what rxn does this enzyme catalyze?
Inhibits DOPA decarboxylase which catalyzes the conversion of DOPA to dopamine.
What enzyme converts dopamine to norepinephrine?
Dopamine Beta-hydroxylase
What causes the condition methylmalonic acidemia? What builds up?
Partial or complete deficiency of methylmalonyl CoA mutase.
Causes build-up of methylmalonic acid and propionic acid.
What is thiamine a cofactor for?
- pyruvate dehydrogenase
- alpha-ketoglutarate dehydrogenase (part of TCA cycle)
- branched chain alpha-ketoglutarate dehydrogenase
- transkelotase (part of pentose phosphate pathway, so it’s crucial for restoration of NADPH)
What enzyme catalyzes the rate limiting step in heme synthesis?
aminolevulinic acid synthase (aka ALA synthase)
How can isoniazid lead to a sideoblastic anemia?
Because it inhibits pyridokine phosphokinase which converts B6 into its active form (pyridoxil 5’ phosphate) and this active form is a necessary cofactor for ALA synthase.
What vitamin is a cofactor for transamination reactions?
Pyridoxine (B6)
What enzymes utilize tetrahydrobiopterin (BH4)?
Phenylalanine hydroxylase (why supplementation of BH4 can help tx PKU), tyrosine hydroxylase, and tryptophan hydroxylase.
What is a cofactor for cystathione synthase and what does deficiency in this enzyme cause?
B6 is a cofactor. Deficiency causes homocystinuria.
What is a cofactor for methionine synthase and what can deficiency in this enzyme cause?
B12 is a cofactor. Deficiency can cause homocystinuria.
______ is the non-toxic carrier of glutamine in the bloodstream that delivers ammonia to the liver for the urea cycle?
Glutamine.
What is the first enzyme in gluconeogenesis and how does acetyl CoA affect it?
Pyruvate carboxylase is the first enzyme and acetyl CoA increases its activity.
Patients with alkaptonuria are deficient in what enzyme?
Homogentisic acid dioxygenase
What does enzyme deficiency in acyl CoA dehydrogenase cause?
Fatty acid dehydrogenase deficiencies where you get hypoglycemic w/o ketones from fasting. Presents similarly to carnitine deficiency.
What is the rate limiting step in fatty acid synthesis?
Acetyl-CoA carboxylase
What does deficiency in hypoxanthine guanine phosphoribosyltransferase cause?
Lesch-Nyhan syndrome
What does deficiency is arylsulfatase A (a lysosomal enzyme) cause? How does it present?
Metachromatic leukodystrophy, an autosomal recessive disorder. Presents w/ demyelination of central and peripheral nerves leading to muscle wasting and ataxic gait.
Macrophages with prominent reddish-pink vacuoles in the cytoplasm after staining with toluidine blue is a key histopathological finding.
What is the histopathological finding in Tay-Sachs?
An “onion-skin” appearance to lysosomes.
What does iduronate sulfatase deficiency cause?
Hunter syndrome
How does arginase deficiency present? How do you tx it?
Progressive spastic diplegia, growth delay and abnormal movements in the setting of high arginine levels.
Tx = arginine free, low protein diet.
