Prosthetic Groups, and Cofactors

Prosthetic groups and coenzymes are complex organic compounds, many of which are derived from vitamins. These compounds are recycled and are needed only in catalytic amounts to convert a large amount of reactants to products. Coenzymes function as substrates in 

These compounds are derived from the vitamin niacin (nicotinic acid, nicotinamide) and require it for their synthesis. Small amounts of niacin are derived from the essential amino acid tryptophan. 

These compounds are derived from the vitamin riboflavin. They are not true nucleotides, because the flavin ring system is attached to ribitol, a sugar alcohol, rather than ribose. 

CHAPTER6 Enzymes I General Properties, Kinetics, and Inhibition 

Metal cofactors in enzymes may be bound reversibly or firmly. Reversible binding occurs in metal-activated enzymes (e.g., many phosphotransferases) firm (or tight) binding occurs in metalloenzymes (e.g., carboxypeptidase A). Metals participate in enzyme catalysis in a number of different ways. An inherent catalytic property of a metal ion may be augmented by the enzyme protein, or metal ions may form complexes with the substrate and the active center of the enzyme and promote catalysis, or metal ions may function in electron transport reactions between substrates and enzymes. 

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Prosthetic groups and cofactors, whether organic or metallic, may be removed from a protein to create an inactive apo protein or enzyme. Loss of these groups may occur through environmental changes, such as removing metal ions from solution or adding denaturants to unfold... 

There is a reasonable argument to suggest that protein prosthetic groups and cofactors should arise in advance of proteins and enzymes, since these are often directly responsible for the chemical reactivity of a given protein, supported by the surrounding polypeptide infrastructure. For this reason prosthetic groups and cofactors are sometimes referred... 

Circumstances of protein function to guide approach and analyses It is possible to consider functional proteins, for example, with their natural prosthetic groups and cofactors, to suggest important variables that relate to function, and these become tools with which to achieve protein engineering (see Tables 5.1 and... 

For example, prosthetic groups and cofactors can be attached to model proteins, and the role of each as regards function can be quantified and utilized. 

Frequently, metal ions are associated with the prosthetic group or cofactor. Heme rings usually contain a chelated iron atom. Occasionally, however, these metals are merely bound within folded polypeptide regions with no additional organic constituents required. Many metal ions are known to participate in enzymatic activity. One or more of the ions of Na, K, Ca, Zn, Cu, Mg, Mn, as well as Co and Mo are often required by enzymes to maintain activity. 

Biosynthesis of Cofactors, Prosthetic Groups, and Carriers Biotin Folic acid... 

Only the enzymes mentioned in this atlas are listed here, from among the more than 2000 enzymes known. The enzyme names are based on the iUBlVlB s of dal Enzyme nomenclature 1992. The additions shown in round brackets belong to the enzyme name, while prosthetic groups and other cofactors are enclosed in square brackets. Common names of enzyme groups are given in italics, and trivial names are shown in quotation marks. 

HETATM lines, which contain the same information as ATOM lines for any nonprotein molecules (cofactors, prosthetic groups, and solvent molecules, collectively called heteromers) included in the structure and listed in HET and FORMUL lines above. 

Phase II Reactions. As with phase I reactions, phase II reactions usually depend on several enzymes with different cofactors and different prosthetic groups and, frequently, different endogenous cosubstrates. All of these many components can depend on nutritional requirements, including vitamins, minerals, amino acids, and others. Mercapturic acid formation can be cited to illustrate the principles involved. The formation of mercapturic acids starts with the formation of glutathione conjugates, reactions catalyzed by the glutathione -transferases. 

Vitamins are essential in mammalian physiology because their coenzyme forms are prosthetic groups or cofactors in many enzyme reactions or because they can perform certain specialized functions in the human organism. Vitamin A and its role in the visual process is an example. The biology of vitamins may be examined from the nutritional or biochemical points of view. The former is concerned with minimum daily requirements, dietary sources, bioavailability, and deficiency syndromes. The biochemist looks for structures, functional groups, conversion to coenzymes, mechanisms of action, mode of transport, and storage. Both aspects will be addressed in this chapter, though the emphasis will be on the biochemical properties of vitamins. 

Flavoenzymes are widespread in nature and are involved in many different chemical reactions. Flavoenzymes contain a flavin mononucleotide (FMN) or more often a flavin adenine dinucleotide (FAD) as redox-active prosthetic group. Both cofactors are synthesized from riboflavin (vitamin B2) by microorganisms and plants. Most flavoenzymes bind the flavin cofactor in a noncovalent mode (1). In about 10% of aU flavoenzymes, the isoalloxazine ring of the flavin is covalently linked to the polypeptide chain (2, 3). Covalent binding increases the redox potential of the flavin and its oxidation power, but it may also be beneficial for protein stability, especially in flavin-deficient environments. 

Yes, Many prosthetic groups and coenz5mies are water-soluble derivatives of vitamins. It should be noted that the main clinical symptoms of dietary vitamin insufficiency generally arise from the malfunction of enzymes, which lack sufficient cofactors derived from vitamins to maintain homeostasis. 

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