SECTION 13. THE HEME AND IRON METABOLISM

Main subjects:

13.1. Heme biosynthesis and regulation

13.2. Iron metabolism

13.3. Disturbances of iron metabolism

13.4. Heme catabolism

13.5. Heme catabolism disturbances. Jaundices

The heme is the prosthetic group of hemoglobin, myoglobin, cytochromes, as well as coenzyme of cat-alase, peroxidase and cytochromoxidase. The heme is synthesized in the most part of cells of the body except for erythrocytes which don't have protein-synthesizing system. The iron necessary for the heme synthesis enters the body with food or is released because of heme degradation.

The heme catabolism in reticuloendothelial system leads to the formation of bile pigment of bilirubin. As the result of consecutive reactions which occur in the liver, intestine and kidney, the bilirubin is converted to the end products of heme catabolism - stercobilin and urobilin excreted from the body in the feces and urine, respectively.

13.1. HEME BIOSYNTHESIS

AND REGULATION

The heme is the porphyrin derivative which built up from 4 pyrrole rings linked by methenyl bridges with the intercalated divalent iron into its structure. Porphyrins differ from each other by the substituents in pyrrole rings. Hemoglobin heme contains protoporphyrin IX including 2 vinyl and 4 methyl radicals, and 2 propionic acid residues (Fig. 13.1).

Fig. 13.1. The structure of hemoglobin heme

The heme of hemoglobin is the cyclic structure; it is pro-toporphyrin IX linked by 2 covalent and 2 coordination bonds with Fe²⁺. Protoporphyrin IX is composed from 4 pyrrole rings linked by methenyl bridges with each other and including 2 vinyl, 4 methyl radicals, and 2 propionic acid residues.

The hemoglobin molecule is composed of 4 hemes and the protein globin is formed by 2б- and 2в-poly-peptide chains. The substrates of the heme synthesis are glycine, succinyl-CoA, and Fe²⁺. The first and lastt hree reactionstake place in mitochondrial matrix, the others occur in the cytoplasm (Fig. 13.2).