Prosthetic group or cofactor

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. 

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. 

In this review the term fluorescent protein refers to proteins being able to autocatalytically form a chromophore, thus possessing the intrinsic property to emit light without the need for any substrate, prosthetic group or cofactor. 

Fig. 2. Tentative scheme for the conversion of glycine to serine associated with the inside of the inner membrane and matrix of plant mitochondria. E, Ej, E3, and E4 are regarded as enzyme proteins with pyridoxal phosphate, lipoyl, possibly tetrahydrofolate and FAD as prosthetic groups or cofactors. The scheme incorporates published information for similar systems in microorganisms, liver mitochondria, and plants and shows the three phosphorylations of ADP to ATP considered to be associated with the reaction in plants.

A molecule of dihydroxyacetone is split from sedo-heptulose-7-phosphate and is condensed with glyceraldehyde in an aldol condensation reaction. Since no free dihydroxyacetone accumulates in the medium, the enzyme has been called transaldolase rather than aldolase, and the formation of a dihydroxyacetone enzyme intermediate has been demonstrated. The enzyme was purified 700 times from yeast and was found to catalyze the reaction without the help of a prosthetic group or cofactor. 

Intrinsic reporter groups are already present in an essential component of the reaction under study. They may be located within the protein, a prosthetic group or cofactor, such as flavins (3), NADH (2), pyridoxal-5 -phosphate (4). or a substrate or other ligand (5). 

Knzyme Prosthetic group or cofactors Products Refs. 

The ability of proteins to bind prosthetic groups or cofactors and other proteins may have led to the development of enzymatic activity. Those proteins (e.g., hemoglobin, etc.) which have both nonenzymatic and enzymatic functions may represent one evolutionary pathway by... 

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... 

As mentioned before, the main problem for the application of such oxidizing enzymes in organic synthesis is the availability of an effective reactivation method for the prosthetic groups or the freely dissociated cofactors. Especially, the long-term stability of the whole system is the limiting factor [25]. All oxidases mentioned previously can be reactivated by an aerobic... 

Biochemically, FMN and FAD act as cofactors, i.e., as covalently bound prosthetic groups, or as noncovalently bound coenzymes in a variety of biological oxidation-reduction reactions, such as ... 

HET and FORMUL lines, listing the cofactors, prosthetic groups, or other nonprotein substances present in the structure. On-line versions of PDB files often contain links to more information about HET groups, including links to graphics displays of their structures (see Chapter 11). 

Because xenobiotic metabolism involves many enzymes with different cofactor requirements, prosthetic groups, or endogenous cosubstrates, it is apparent that many different nutrients are involved in their function and maintenance. Determination of the effects of deficiencies, however, is more complex because reductions in activity of any particular enzyme will be effective only if it affects a change in a rate-limiting step in a process. In the case of multiple deficiencies, the nature of the rate-limiting step may change with time... 

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. 

The ultimate identification of a particular enzyme is possible through its Enzyme Commission (E.C.) number.2 The assignment of E.C. numbers is described in guidelines set out by the International Union of Biochemistry, and follows the format E.C. w.x.y.z, where numerical values are substituted for w, x, y and z. The value of w is always between 1 and 6, and indicates one of six main divisions values of x indicate the subclassification, and are often related to either the prosthetic group or the cofactor required for the reaction values of y indicate a subsubclassification, related to a substrate or product family and the value of z indicates the serial number of the enzyme. 

Reaction specificity is the most significant and most widespread classification of enzymes (Tab. 3.10). Another way of classifying enzymes is by their complexity (Tab. 3.11). As already pointed out, enzymes are proteins or at least consist predominantly of a protein portion. Some enzymes need cofactors (prosthetic groups or cosubstrates see Tab. 3.11). 

Protein enzymes frequently operate with the help of metal ions and with that of organic cofactors, which either are covalently bound to the enzyme molecule (prosthetic groups) or act in free, soluble form (coenzymes). As is to be expected, these cofactors serve mostly as carriers in transfer reactions. Several are nucleotide derivatives or have a nucleotide-like structure, thus being related to nucleic acid components. Many contain a vitamin in their molecule. 

Many enzymes are initially synthesized as inactive forms, which require exogenous cofactors for their activity. Only after the inactive apoprotein combines with the cofactor it becomes the active holoenzyme. Cofactors may be dissociable or tightly bound with the latter often referred to as a prosthetic group. A cofactor may be a metal (e.g., iron or copper), an organic compound (e.g., pyridoxal phosphate or flavin), or an organometallic compound (e.g., heme or cobalamin). Cofactors are necessary to assist amino acid residues at the active sites... 

Coenzymes, then, are a type of cofactor. They are small organic molecules that bind tightly (prosthetic groups) or loosely (cosubstrates) to enzymes as they participate in catalysis, see also Active Site Cofactor Enzymes. 

Many proteins function as enzymes and are, therefore, the most important biocatalysts found in organisms. Of course, the enzymes often contain additional components which act as cofactors (firmly linked as prosthetic groups or reversibly bound as coenzymes). The cofactors are not proteins rather, they are macro- or micronutrient elements, or small molecules which contain such elements, and are essential for correct functioning of the enzyme. In addition there are effectors which either increase or... 

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