Hemes, Inborn Errors of Metabolism, Misc

Question 0

Creatine Breakdown

Answer 0

Creatine –> Creatine Phosphate (Via Creatine Phosphokinase)

Creatine Phosphate –> Creatinine (nonenzymatically)

Question 1

What is creatine made of?

Answer 1

Glycine and Arginine, then methylated with SAM

Question 2

Creatine Phosphate Function

Answer 2

Storage form of ATP during ischemia (infarct, stroke, etc.)

Question 3

Creatinine

Answer 3

Good indication of kidney function and urinary flow.

Question 4

Nitric Oxide is made from…

Answer 4

Arginine and NADPH via NO Synthase (Uses THB).

NO is the major reactive nitrogen radical. Acts as a smooth muscle relaxant, vasodilator, also prevents platelet aggregation.

Question 5

Heme Structure

Answer 5

4 Pyrrole rings with center iron, which is a porphyrin ring. Synthesized in liver for CYP450 enzymes, and synthesized in liver for hemaglobin.

Question 6

Heme Synthesis

Answer 6

In mitochondria: Succinyl CoA + Glycine —> ALA (via ALA synthase). This is the rate limiting step and is inhibited by heme.

ALA moves to the cytoplasm, where it reacts with another ALA via ALA dehydratase to create Porphobilinogen. This step is blocked by lead poisoning.

4 PBG’s fuse to form hydroxybilane, which, after ring closing, is uroporphyrinogen III. Eventually, after becoming coproporphyrinogen, protoporphyrinogen moves back into the mitochondria, where it becomes protoporphyrin. It receives its Fe via Ferrochelatase. This final step is blocked by lead poisoning and end product inhibition.

Question 7

Porphyrias

Answer 7

Diseases of heme synthesis enzymes.

Question 8

Heme Breakdown

Answer 8

Occurs in spleen and liver. Heme loses its Fe and O2 via heme oxygenase, and becomes biliverdin. Biliverdin is reduced by NADPH to become bilirubin (via biliverdin reductase). Bilirubin is then carried by albumin in the blood, is conjugated by UDP-Glucuronate to become Biliruvin Diglucuronide in the liver, which is very soluble. Can then be excreted after use as bile pigments, as urobilinogen and stercobilin.

Question 9

PKU

Answer 9

Due to a defect in phenylalanine dehydroxylase (uses THB). Restrict phe in diet and give Kuvan (THB).

Question 10

Propionic Acidemia

Answer 10

Defect in Propionyl CoA reductase, which converts propionyl CoA to methylmalonyl Coa from Valine, Odd chains, Met, Iso, Thr.

Question 11

OTC Deficiency

Answer 11

Deficiency in ornithine transcarbamylase which converts ornithine and carbamoyl phosphate into citrulline. Need to restrict all AA’s and give citrulline. Dialysis to remove ammonia and drugs like benzoate to drive ammonia excretion.

Question 12

Galactosemia

Answer 12

No UDP-Glucose:Gal-1-P Uridylyltransferase.

Question 13

MCAD

Answer 13

Medium Chain Acyl CoA Dehydrogenase Deficiency. Fatty acid breakdown issues. Don’t fast.