Aerobic metabolism biosynthesis

Heme A is an obligatory cofactor in all eukaryotic and most bacterial cytochrome c oxidase enzymes (CcO). Because of its importance to CcO and aerobic metabolism, considerable effort has recently been invested in understanding the mechanism and regulation of heme A biosynthesis. The activity of heme A synthase is strictly dependent on O2, and yet there is no incorporation of O2 into the products. Heme A synthase is now known to utilize a unique electron-transfer mechanism when oxidizing heme O to heme A. Interestingly, the heme A biosynthetic pathway is regulated at least partly via a heme-dependent process in which heme A synthase is positively regulated by intracellular heme levels via Hapl. 

Despite the critical importance of heme A to aerobic metabolism, many gaps remain in our understanding of heme A biosynthesis, regulation, and transport. This chapter summarizes recent progress in the field and our current understanding of the heme A biosynthetic pathway. 

During aerobic metabolism, the O2 released by photosynthesis as a waste product is used to oxidize carbohydrates to CO2, driving biological processes such as biosynthesis, muscle contraction, cell division, and nerve conduction. Hence, the sustenance of life on Earth depends on a tightly regulated carbon-oxygen cycle that is driven by solar energy. 

A schematic block diagram of the metabolism of a typical aerobic heterotroph. The block labeled Catabolism represents pathways by which nutrients are converted to small-molecule starting materials for biosynthetic processes. Catabolism also supplies the energy (ATP) and reducing power (NADPH) needed for activities that occur in the second block these compounds shuttle between the two boxes. The block labeled Biosynthesis represents the synthesis of low- to medium-molecular-weight components of the cell as well as the synthesis of proteins, nucleic acids, lipids, and carbohydrates and the assembly of membranes, organelles, and the other structures of the cell. 

The first sub-cellular organelle to be isolated (other than the nucleus), mitochondria are the powerhouse of the cell, generating ATP through aerobic oxidative phosphorylation the TCA (Krebs) cycle (the hub of metabolism ) and fatty acid oxidation take place entirely within mitochondria. Other pathways and cycles (urea cycle, haem biosynthesis, cardiohpin synthesis, quinone and steroid biosynthesis) include steps both outside and inside the mitochondria. 

Sulfate reduction. All plants, animals, and bacteria metabolize sulfur in order to synthesize amino acids such as cysteine and methionine. The sulfur may be assimilated as sulfate or as organic molecules containing sulfate. The reduction of sulfate in biosynthesis is termed assimilatory sulfate reduction and can take place in aerobic or anaerobic environments (cf. Goldhaber and Kaplan 1974 Rheinheimer 1981 Cullimore 1991). 

In nature, oxidation reactions are essential for aerobic life. Energy for cells is provided by the combustion of carbohydrates and fatty acids with dioxygen. Oxidation reactions are also involved in biosynthesis, metabolism reactions, and the detoxification of harmful compounds. In several of these reactions, iron or manganese enzymes are involved. These manganese and iron enzymes have frequently been used as a source of inspiration for the development of manganese- and iron-based oxidation catalysts. 

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