Biochemistry (cofactors and deficiencies)

Question 1

What is biotin (B7) a cofactor for?

Answer 1

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)

Question 2

What enzyme is B6 a cofactor for? What does the enzyme do?

Answer 2

Alanine transaminase. Catalzyes the reversible reaction from pyruvate and glutamate to alanine and alpha-ketoglutarate.

Question 3

Heme is broken down to biliverdin by what enzyme?

Biliverdin is broken down into unconjugated bilirubin by what enzyme?

Answer 3

Heme –> biliverdin = heme oxygenase

biliverdin –> unconjugated bili = biliverdin reductase

Question 4

Tyrosinase deficiency causes what disorder?

Answer 4

Albinism. This is because this enzyme functions in the pathway of melanin production from DOPA or tyrosine as a substrate.

Question 5

What enzyme does carbidopa inhibit and what rxn does this enzyme catalyze?

Answer 5

Inhibits DOPA decarboxylase which catalyzes the conversion of DOPA to dopamine.

Question 6

What enzyme converts dopamine to norepinephrine?

Answer 6

Dopamine Beta-hydroxylase

Question 7

What causes the condition methylmalonic acidemia? What builds up?

Answer 7

Partial or complete deficiency of methylmalonyl CoA mutase.

Causes build-up of methylmalonic acid and propionic acid.

Question 8

What is thiamine a cofactor for?

Answer 8

• 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)

Question 9

What enzyme catalyzes the rate limiting step in heme synthesis?

Answer 9

aminolevulinic acid synthase (aka ALA synthase)

Question 10

How can isoniazid lead to a sideoblastic anemia?

Answer 10

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.

Question 11

What vitamin is a cofactor for transamination reactions?

Answer 11

Pyridoxine (B6)

Question 12

What enzymes utilize tetrahydrobiopterin (BH4)?

Answer 12

Phenylalanine hydroxylase (why supplementation of BH4 can help tx PKU), tyrosine hydroxylase, and tryptophan hydroxylase.

Question 13

What is a cofactor for cystathione synthase and what does deficiency in this enzyme cause?

Answer 13

B6 is a cofactor. Deficiency causes homocystinuria.

Question 14

What is a cofactor for methionine synthase and what can deficiency in this enzyme cause?

Answer 14

B12 is a cofactor. Deficiency can cause homocystinuria.

Question 15

______ is the non-toxic carrier of glutamine in the bloodstream that delivers ammonia to the liver for the urea cycle?

Answer 15

Glutamine.

Question 16

What is the first enzyme in gluconeogenesis and how does acetyl CoA affect it?

Answer 16

Pyruvate carboxylase is the first enzyme and acetyl CoA increases its activity.

Question 17

Patients with alkaptonuria are deficient in what enzyme?

Answer 17

Homogentisic acid dioxygenase

Question 18

What does enzyme deficiency in acyl CoA dehydrogenase cause?

Answer 18

Fatty acid dehydrogenase deficiencies where you get hypoglycemic w/o ketones from fasting. Presents similarly to carnitine deficiency.

Question 19

What is the rate limiting step in fatty acid synthesis?

Answer 19

Acetyl-CoA carboxylase

Question 20

What does deficiency in hypoxanthine guanine phosphoribosyltransferase cause?

Answer 20

Lesch-Nyhan syndrome

Question 21

What does deficiency is arylsulfatase A (a lysosomal enzyme) cause? How does it present?

Answer 21

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.

Question 22

What is the histopathological finding in Tay-Sachs?

Answer 22

An “onion-skin” appearance to lysosomes.

Question 23

What does iduronate sulfatase deficiency cause?

Answer 23

Hunter syndrome

Question 24

How does arginase deficiency present? How do you tx it?

Answer 24

Progressive spastic diplegia, growth delay and abnormal movements in the setting of high arginine levels.

Tx = arginine free, low protein diet.

Question 25

What does PBG Deaminase deficiency cause and how does it present?

Answer 25

Causes acute intermittent porphyria which presents w/ acute attacks of abdominal pain, neuropsychiatric sxs, and red-brown urine.

Question 26

What does uroporphyrinogen decarboxylase deficiency cause?

Answer 26

Porphyria cutanea tarda which presents w/ chronic blistering photosensitivity in sun exposed areas and uroporphyrinogen in the urine.

Question 27

What is acid maltase?

Answer 27

It is the enzyme that is deficient in Pompe disease. It is a lysosomal enzyme w/ a1-4 and a1-6 glucosidase activity.

Question 28

What reaction does enolase catalyze?

Answer 28

COnversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis