Covers porphyrins as precursors of heme, where they are made in the liver and in erythroid marrow, and the stepwise route from glycine and succinyl-CoA through ALA, porphobilinogen, uroporphyrinogen III and protoporphyrin IX to iron insertion by ferrochelatase. It then outlines the porphyrias by enzyme deficiency, with symptoms and accumulated precursors for acute intermittent, cutaneous tarda, congenital erythropoietic and erythropoietic protoporphyria.
Topic 60 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 3 sections, about 295 words (2 min of reading), with 10 flashcards.
In this note
Biosynthesis of Porphyrin. Porphyrias
Biosynthesis of Porphyrins
Clinical Relevance: Porphyrias
Biosynthesis of Porphyrins
Porphyrins are cyclic compounds that serve as precursors for heme, chlorophyll, and other important cofactors.
In humans, porphyrins are mainly synthesized for heme production (for hemoglobin, myoglobin, cytochromes, and catalase).
Site of Synthesis
Liver: for cytochromes and detoxification enzymes.
Bone marrow (erythroid cells): for hemoglobin synthesis.
Mitochondria and cytosol are both involved in steps of synthesis.
Stepwise Biosynthesis of Heme
Formation of δ-Aminolevulinic Acid (ALA)
First and rate-limiting step
Enzyme: ALA synthase (mitochondrial)
Substrates: Glycine + Succinyl-CoA
Cofactor: Vitamin B6 (Pyridoxal phosphate)
Regulation:
Inhibited by heme (negative feedback)
Induced by certain drugs, hormones (glucocorticoids, barbiturates)
Formation of Porphobilinogen (PBG)
Enzyme: ALA dehydratase (cytosolic)
Two ALA molecules condense to form porphobilinogen.
Formation of Hydroxymethylbilane
Four molecules of PBG are condensed → linear tetrapyrrole (hydroxymethylbilane).
Enzyme: PBG deaminase (uroporphyrinogen I synthase).
Formation of Uroporphyrinogen III
Cyclization and isomerization → uroporphyrinogen III (physiologically active).
Enzyme: uroporphyrinogen III synthase
Formation of Coproporphyrinogen III
Decarboxylation of uroporphyrinogen III → coproporphyrinogen III.
Enzyme: uroporphyrinogen decarboxylase
Formation of Protoporphyrin IX
Coproporphyrinogen III enters mitochondria → oxidized to protoporphyrin IX.
