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heme

Monday 6 October 2003

A heme (or haem) is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin.

Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins.

Structure

Function

Members

- heme A

Heme synthesis (porphyrin synthesis)

The enzymatic process that produces heme is properly called porphyrin synthesis, as all the intermediates are tetrapyrroles that are chemically classified are porphyrins. The process is highly conserved across biology. In humans, this pathway serves almost exclusively to form heme. In other species, it also produces similar substances such as cobalamin (vitamin B12).

The pathway is initiated by the synthesis of D-Aminolevulinic acid (dALA or δALA) from the amino acid glycine and succinyl-CoA from the citric acid cycle (Krebs cycle). The rate-limiting enzyme responsible for this reaction, ALA synthase, is strictly regulated by intracellular iron levels and heme concentration.

A low-iron level, e.g., in iron deficiency, leads to decreased porphyrin synthesis, which prevents accumulation of the toxic intermediates. This mechanism is of therapeutic importance: infusion of heme arginate of hematin can abort attacks of porphyria in patients with an inborn error of metabolism of this process, by reducing transcription of ALA synthase.

The organs mainly involved in heme synthesis are the liver and the bone marrow, although every cell requires heme to function properly. Heme is seen as an intermediate molecule in catabolism of haemoglobin in the process of bilirubin metabolism.

Heme degradation

In the first step, heme is converted to biliverdin by the enzyme heme oxygenase (HOXG). NADPH is used as the reducing agent, molecular oxygen enters the reaction, carbon monoxide is produced and the iron is released from the molecule as the ferric ion (Fe3+).

In the second reaction, biliverdin is converted to bilirubin by biliverdin reductase (BVR).

Bilirubin (free bilirubin) is transported into the liver bound to a protein (serum albumin), where it is conjugated with glucuronic acid to become more water soluble (conjugated bilirubin). The reaction is catalyzed by the enzyme UDP-glucuronide transferase (UDPGUTF).

This form of bilirubin is excreted from the liver in bile. The intestinal bacteria deconjugate bilirubin diglucuronide and convert bilirubin to urobilinogens.

Some urobilinogen is absorbed by intestinal cells and transported into the kidneys and excreted with urine, in which it forms the yellow color. The remainder travels down the digestive tract and is excreted as stercobilinogen, which is responsible for the color of feces.

Pathology

- anomalies of heme metabolism

  • anomalies of heme synthesis
  • anomalies of heme degradation

See also

- hemoproteins