Heme Transport and Incorporation into Proteins

Heme proteins are located in different compartments and organelles of pro- and eukaryotic cells. For their biosynthesis and assembly heme needs to be delivered to the polypeptides at the correct location. As heme is a hydrophobic molecule, it readily partitions into membranes and is bound to proteins, and the concentration of the free molecule in cells is extremely low. Heme is synthesized from the precursor 5-aminolevulinic acid, with the last step taking place in mitochondria in animals and fungi, and the plastid in plants. Some cells have the capability of taking heme up from the environment. The question therefore arises, how is heme transported across membranes and cellular compartments to its target proteins? The assembly of heme with these proteins is rather specific, and in many cases even stereospecific. For type c-type cytochromes, which bind heme covalendy, specialized maturation systems have evolved that catalyze heme incorporation. It is likely that other heme proteins also need appropriate assembly factors for heme insertion. The current knowledge of intracellular heme transport and the biogenesis of heme-containing proteins is limited, and has only recently been recognized as an attractive field of research.

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