porphyrins

Definition: A porphyrin is a heterocyclic macrocycle derived from four pyrroline subunits interconnected via their α carbon atoms via methine bridges (=CH-).

Porphyrins are aromatic and they obey Hückel’s rule for aromaticity in that they possess 4n+2 pi electrons which are delocalized over the macrocycle.

The macrocycle, therefore, is a highly-conjugated system, and, as a consequence, is deeply coloured - the name porphyrin comes from a Greek word for purple. The macrocycle has 22 pi electrons.

The parent porphyrin is porphine, and substituted porphines are called porphyrins. Many porphyrins occur in nature, such as in green leaves and red blood cells, and in bio-inspired synthetic catalysts and devices.

Metals

Porphyrins bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+, is in the central N4 cavity formed by the loss of two protons. Most metals can be inserted. A schematic equation for these syntheses is shown:

H2porphyrin + [MLn]2+ → M(porphyrinate)Ln-4 + 4 L + 2 H+

A porphyrin in which no metal is inserted in its cavity is sometimes called a free base.

Heme

Some iron-containing porphyrins are called hemes; and heme-containing proteins, or hemoproteins, are found extensively in nature. Hemoglobin and myoglobin are two O2-binding hemoproteins that contain iron porphyrins.

Porphyrin biosynthesis

The "committed step" for porphyrin biosynthesis is the formation of D-aminolevulinic acid (dALA) by the reaction of the amino acid glycine and succinyl-CoA, from the citric acid cycle.

Two molecules of dALA combine to give porphobilinogen (PBG), which contains a pyrrole ring.

Four PBGs are then combined through deamination into hydroxymethyl bilane (HMB), which is hydrolysed to form the circular tetrapyrrole uroporphyrinogen III.

This molecule undergoes a number of further modifications. Intermediates are used in different species to form particular substances, but, in humans, the main end-product protoporphyrin IX is combined with iron to form heme. Bile pigments are the breakdown products of heme.

Pathology: porphyrias

The anomalies of heme biosynthesis are porphyrias.

Enzyme	Substrate	Product	Chromosome	EC	OMIM	Porphyria
ALA synthase	Glycine, succinyl CoA	D-Aminolevulinic acid	3p21.1	2.3.1.37	MIM.125290	none
ALA dehydratase	D-Aminolevulinic acid	Porphobilinogen	9q34	4.2.1.24	MIM.125270	ALA-Dehydratase deficiency
PBG deaminase	Porphobilinogen	Hydroxymethyl bilane	11q23.3	2.5.1.61	MIM.176000	acute intermittent porphyria
Uroporphyrinogen III synthase	Hydroxymethyl bilane	Uroporphyrinogen III	10q25.2-q26.3	4.2.1.75	MIM.606938	congenital erythropoietic porphyria
Uroporphyrinogen III decarboxylase	Uroporphyrinogen III	Coproporphyrinogen III	1q34	4.1.1.37	MIM.176100	porphyria cutanea tarda
Coproporphyrinogen III oxidase	Coproporphyrinogen III	Protoporphyrinogen IX	3q12	1.3.3.3	MIM.121300	coproporphyria
Protoporphyrinogen oxidase	Protoporphyrinogen IX	Protoporphyrin IX	1q22	1.3.3.4	MIM.600923	variegate porphyria
Ferrochelatase	Protoporphyrin IX	Heme	18q21.3	4.99.1.1	MIM.177000	erythropoietic protoporphyria