Riboflavine, structure, function

In this section we provide an overview of recent approaches that have contributed to clarify riboflavin eflects in MADD, one focusing on global pro-teomic responses upon riboflavin supplementation and the other detailing the molecular rationale for such eflects in respect to consequences on the structure, function and folding of ETF. 

Flavin analogs are of special use in the study of structure/function relationship within different flavin dependent enzymes. Even before 1989, a variety of flavin analogs at the riboflavin, FMN, and FAD level were separated, quantitated, or isolated by FIPLC, including 5-deazaflavin, 1-deazaflavin, and malonylriboflavin (85). A simultaneous separation of 12 different flavin analogs by reversed-phase FIPLC is demonstrated in Figure 11 (85). 

Thiobacillus ferrooxidans function. 6, 651 Rhus vernicifera stellacyanin structure, 6,651 Riboflavin 5 -phosphate zinc complexes, 5,958 Ribonucleotide reductases cobalt, 6,642 iron, 6,634... 

Flavin coenzymes are usually bound tightly to proteins and cycle between reduced and oxidized states while attached to the same protein molecule. In a free unbound coenzyme the redox potential is determined by the structures of the oxidized and reduced forms of the couple. Both riboflavin and the pyridine nucleotides contain aromatic ring systems that are stabilized by resonance. Part of this resonance stabilization is lost upon reduction. The value of E° depends in part upon the varying amounts of resonance in the oxidized and reduced forms. The structures of the coenzymes have apparently evolved to provide values of E° appropriate for their biological functions. 

Structures of the vitamin riboflavin (a) and the derived flavin coenzymes (b). Like NAD+ and NADP+, the coenzyme pair FMN and FAD are functionally equivalent coenzymes, and the coenzyme involved with a given enzyme appears to be a matter of enzymatic binding specificity. The catalytically functional portion of the coenzymes is shown in red. 

Therapeutic Function Enzyme cofactor vitamin source Chemical Name Riboflavin monomethylol Common Name -Structural Formula ... 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Riboflavin, physiology and biochemistry of formation 84PHA805. Tocopherol, chemistry and natural occurrence of 81KPS263. Tocopherol, structure and functions of 86ACR194. 

A. Bacher H. Schnepple B. Mailaender M. K. Otto Y. Ben-Shaul, Structure and Function of the Riboflavin Synthase Complex ot Bacillus subtilis. In Elavins Flavoproteins, Proceedings of the 6th International Symposium, 1980, pp 579-586. 

A fold also can be formed by one domain. In the example of secondary structures provided by lactate dehydrogenase (see Fig. 7.8), domain 1 alone forms the nucleotide binding fold. This fold is a binding site for NAD or, in other proteins, molecules with a generally similar structure (e.g., riboflavin). However, many proteins that bind NAD or NADP contain a very different fold from a separate fold family. These two different NAD binding folds arise from different ancestral lines and have different structures, but have similar properties and function. They are believed to be the product of convergent evolution. 

The 1930s were a golden age for the discoveries of structures and functions of other vitamins. In 1935, the laboratories of both Kuhn and Karrer reported synthesis of vitamin B2 (riboflavin, see the strucmre below). Two years earlier Warburg found a yellow oxidative enzyme in bottom yeasts and Kuhn identified it as vitamin B2. Its REDOX role in the metabolism of carbohydrates, fats, and proteins would soon be under-... 

Figure 3.8. Structures of vitamins or vitamin-derived molecules that function in oxidation-reduction reactions. The oxidation of these redox groups in the inner mitochondricil membrane contributes to the electron transport chain that carries electrons from the oxidation of glucose to oxygen and in the process pumps protons from one side to the other of the inner mitochondrial membrane (see Chapter 8 for details). The proton gradient thus formed is used to phosphorylate ADP to form 32 of the 36 ATPs resulting from the oxidation of one glucose molecule to six CO2 and six H2O molecules. A Vitamin B3, also called niacin or nicotinic acid, becomes converted to the amide (nicotinamide) and dressed up with a ribose sugar. Then, in a manner like that of riboflavin in B becomes phosphorylated to form nicotinamide mononucleotide (NMN) or further reacted with the addition of adenosine monophosphate (AMP) to form nicotinamide adenine dinucleotide (NAD). B Vitamin B2, also known as riboflavin, is shown converted to the forms involved in redox reactions such as those of the electron transport chain. (From Biochemistry, Second Edition, D. Voet and J. Voet, Copyright 1995, John Wiley Sons, New York. Reprinted with permission of John Wiley Sons, Inc.)...

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