To read the complete version access from the following link:
An excerpt of the lecture note:
Metabolism of Heme
Heme’s function is to transport O2 in our body. O2 is insoluble in our body. Heme is also insoluble but in globular form, hemoglobin, it becomes soluble.
It functions as a prosthetic group of biological and chemical importance.
HbA is the most common form of heme (>98%):
· α2β2 (4 polypeptides)
· α2 is made up of 141 amino acids, β2 146 amino acids.
· Molecular weight: 66,000
· ~400 variants
Congenital or acquired deficiency of enzymes needed for heme synthesis. This would cause accumulation of heme precursors in blood, uring and CSF. Thus, there is increased excretion of these precursors in feces or urine. High concentration of heme is toxic and can cause various problems including mental retardation.
1. Porphyria cutania tarda is the most common type.
Cause: Iron overload inhibiting production of uroporphyrinogen decarboxylase ↓. As a result, heme precursors and porphyrin gets deposited under skin. Under sunlight these become oxidized and damages cell.
Symptoms: Sunlight hypersensitivity. Urine color would be black/brown, because of oxidized porphyrin in. It is more severe for alcoholics with severe hepatic damage.
Cure: Avoid drinking, avoid sunlight, phlebotomy (puncture blood vessel to decrease iron level in blood)
2. Acute intermittent porphyria
Cause: Uroporphyrinogen synthase deficiency.
a. Visceral: abdominal pain, vomiting
b. CNS: Agitation, seizure, mental retardation
c. Sympathetic: Tachycardia, hypertension
d. Peripheral nervous system: Muscle weakness, paresthesia (tickling or burning sensation of skin)
c. Hypnotics (like barbiturates or phenytoin, Griseofulvin)
a. Hematin (inhibits ALA synthase to decrease heme precursor levels)
b. High carbohydrate infusion
c. Stop taking drugs that might be causing the problem