Coenzymes evolution

In terms of coenzyme evolution, it is also noteworthy that the biosynthesis of a given coenzyme frequently requires the cooperation of other coenzymes. For example, the biosynthesis of riboflavin (24) requires tetrahydrofolate (33) for the biosynthesis of GTP serving as precursor (Fig. 3). Pyridoxal 5 -phosphate is required for the biosynthesis of the activated pyrosulfide type protein (2) that serves as the common precursor for iron/sulfur clusters and various sulfur-containing organic coenzymes (Fig. 1). 

We next focus on the use of fixed-site cofactors and coenzymes. We note that much of this coenzyme chemistry is now linked to very local two-electron chemistry (H, CH3", CH3CO-, -NH2,0 transfer) in enzymes. Additionally, one-electron changes of coenzymes, quinones, flavins and metal ions especially in membranes are used very much in very fast intermediates of twice the one-electron switches over considerable electron transfer distances. At certain points, the chains of catalysis revert to a two-electron reaction (see Figure 5.2), and the whole complex linkage of diffusion and carriers is part of energy transduction (see also proton transfer and Williams in Further Reading). There is a variety of additional coenzymes which are fixed and which we believe came later in evolution, and there are the very important metal ion cofactors which are separately considered below. 

In evolution parts of the code, even parts essential for independent functioning, have been lost so that higher organisms are dependent on vitamins, for example for coenzymes, and on amino acids, lipids and saccharides, or even on selenium incorporation, from other forms of life. This is selective loss in an environment of supportive organisms. Can this be random ... 

Cukovic, D. et al.. Structure and evolution of 4-coumarate coenzyme A ligase (4CL) gene families. Biol Chem., 382, 645, 2001. 

Oxidative phosphorylation produces most of the ATP made in aerobic cells. Complete oxidation of a molecule of glucose to C02 yields 30 or 32 ATP (Table 19-5). By comparison, glycolysis under anaerobic conditions (lactate fermentation) yields only 2 ATP per glucose. Clearly, the evolution of oxidative phosphorylation provided a tremendous increase in the energy efficiency of catabolism. Complete oxidation to C02 of the coenzyme A derivative of palmitate (16 0), which also occurs in the mitochondrial matrix, yields 108 ATP per palmitoyl-... 

SHELLEY D. COPLEY is a professor of molecular, cellular and developmental biology at the University of Colorado at Boulder. Her research interests center on the molecular evolution of enzymes and metabolic pathways and protein structure-function relationships. Dr. Copley is a member of the Council of Fellows of the University of Colorado s Cooperative Institute for Research in Environmental Sciences. Dr. Copley served on the NSF Molecular Biochemistry Panel (1999-2003), was co-chair for the Gordon Conference on Enzymes, Coenzymes, and Metabolic Pathways (2004), and currently serves on the National Institutes of Health Genetic Variation and Evolution Study Section. 

White, H.B. 1976. Coenzymes as fossils of an earlier metabolic age. Journal of Molecular Evolution, 7, 101-104. 

Of some relevance to this review is adenine, which is a component of nucleic acids, and of key nucleotide coenzymes like NAD". This base, and its nucleosides and nucleotides 35>, exhibit a single reduction wave, with about the same total current as the parent purine, of the magnitude expected for a 4e process15,153). On controlled-potential electrolysis, however, it undergoes a 6e reduction to give the same product as does purine in its overall 4e reduction 15,35,36 153), as shown in Scheme 25. The reduction of adenine is accompanied by catalytic hydrogen evolution, so that it is not possible to determine directly the number of electrons involved. 

In the mimicking of an enzymatic process there is no need to copy the structure of protein and coenzyme groups and all stages of this process. In the course of evolution, Nature created enzymes in specific conditions in certain media and utilized certain building materials . Besides chemical functions, enzymes bear many other obligations, serving as units of complicated enzymatic and membrane ensembles. These conditions have not always been the most favorable for catalytic properties and the stability of enzymes. 

Several coenzymes are involved in the biosynthesis of their own precursors. Thus, thiamine is the cofactor of the enzyme that converts 1-deoxy-D-xylulose 5-phosphate (43) (the precursor of thiamine pyrophosphate, pyridoxal 5 -phosphate and of iso-prenoids via the nomnevalonate pathway) into 2 C-methyl-D-erythritol 4-phosphate (90, Fig. 11). Similarly, two enzymes required for the biosynthesis of GTP, which is the precursor of tetrahydrofolate, require tetrahydrofolate derivatives as cofactors (Fig. 3). When a given coenzyme is involved in its own biosynthesis, we are faced with a hen and egg problem, namely how the biosynthesis could have evolved in the absence of the cmcially required final product. The answers to that question must remain speculative. The final product may have been formed via an alternative biosynthetic pathway that has been abandoned in later phases of evolution or that may persist in certain organisms but remains to be discovered. Alternatively, the coenzyme under study may have been accessible by a prebiotic sequence of spontaneous reactions. An interesting example in this respect is the biosynthesis of flavin coenzymes, in which several reaction steps can proceed without enzyme catalysis despite their mechanistic complexity. 

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