Page 28 - Clinical biochemistry

Regulation of heme synthesis

• The first enzyme in this sequence i.e. ALA synthase is the key regulatory
enzyme for heme synthesis.

• It is inhibited by heme, the end product of the metabolism.

Inhibitors of heme synthesis

The following substances inhibit heme synthesis
• Succinylacetone is an inhibitor of heme synthesis that acts on the enzyme
aminolevulinic acid dehydratase.
• N-methyl mesoporphyrin IX blocks iron insertion into protoporphyrin IX
and thus acts as an inhibitor of heme synthesis.
• Isonicotinic acid hydrazide is an inhibitor of 6-aminolevulinic acid
synthase.
Disorders related to abnormalities in the synthesis of porphyrins

Porphyria’s
• Porphyria’s are a group of diseases in which there is an increased excretion
of porphyrins or porphyrin precursors (intermediates of porphyrin synthesis).
• About 85% of heme synthesis occurs in erythrocyte precursors and 15% in
liver.
• Therefore porphyria’s are classified into two types (1) Erythropoietic and (2)
Hepatic.
• Some of them are inherited while others are acquired.

Hemoglobin Derivatives

There are some derivatives of normal Hb that arise due to metabolic changes in the
RBC.

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