ABSTRACT

Heme is a macromolecule found in all mammalian cells and is essential for life. Its major role is in the transport and delivery of oxygen to cells and also in oxidative metabolism. Heme-containing molecules include but are not limited to:

• Hemoglobin, neuroglobin, cytoglobin

• Myoglobin

• Cytochromes a, a + c3 (cytochrome oxidase), b, b5, and c1, other hemoproteins

• Cytochrome P450-linked enzymes

• Oxidative enzymes, for example catalase Heme consists of a porphyrin ring chelated to iron using the nitrogen atoms

of the four cyclic tetrapyrrole rings. The most common type of heme, heme B (ferroprotoporphyrin IX), is shown in Figure 16.1; the six β substituents are four methyl, two vinyl, and two propionyl groups. No function is known in man for porphyrins other than as part of the heme molecule and the biosynthetic route is unique to this molecule. Heme is synthesized in all cells for assembly into mitochondrial cytochromes, but the major sites of synthesis are liver (50 mg/day) and erythrocyte precursor cells (300 mg/day in bone marrow). Total heme production in erythropoietic cells reflects cell number. A deficiency in any of the

N

Fe2+

N

N N

H3C

H3C

CH3

OHOH OO

CH3 CH2

CH2

Figure 16.1 Structure of heme (ferroprotoporphyrin IX). Heme is a conjugated porphyrin in which a single ferrous iron (Fe2+) is chelated to each nitrogen atom of the four tetrapyrrole rings. Substituents on the individual pyrrole rings are methyl and either vinyl or propionyl.