Cofactor coenzyme

Definition of a cofactor, coenzyme, and pros thetic group Some enzymes require cofactors for activity. These can be metal ions or organic molecules called coenzymes that are often derivatives of vitamins. Tightly bound coen zymes are called prosthetic groups. 

Some enzymes require cofactors for the activities Enzymes that require covalent cofactors (prosthetic groups, e.g., heme in cytochromes) or non-covalent cofactors (coenzymes, e.g., NAD(P)+ in dehydrogenases) for activities are called haloenzymes (or simply enzymes). The protein molecule of a haloenzyme is termed proenzyme. The prosthetic group/coenzyme dictates the reaction type catalyzed by the enzyme, and the proenzyme determines the substrate specificity. 

Some non-enzymatic antioxidants play a key role in these defense mechanisms. These are often vitamins (A, C, E, K), minerals (zinc, selenium), caretenoids, organosulfur compounds, allyl sulfide, indoles, antioxidant cofactors (coenzyme Qio)> and polyphenols (flavonoids and phenolic acids) [1,37]. Further, there is good evidence that bilirubin and uric acid can act as antioxidants to help neutralize certain free radicals [38]. Alpha-carotene, lycopene, lutein, and zeaxanthine [39] can be considered subgroups of carotenoids [40] that are effective antioxidant compounds. 

The terms cofactor, coenzymes, and prosthetic group are used to describe the nonprotein moieties of the enzyme active center. The distinction between these terms is not sharp. Some of the cofactors are derivatives of vitamins that form either covalent or noncovalent linkages at or near the active site of the enzyme, and some are metal ions. If a cofactor (coenzyme) is tightly bound to the protein moiety (the apoenzyme), it is often referred to as a prosthetic group. A coenzyme that is easily removed from the holoenzyme, leaving behind the apoenzyme, is often regarded as a second substrate. 

However, this reaction is in fact the sum of five reactions catalyzed by three enzymes and requiring five cofactors coenzyme A (CoA), NAD+, FAD, thiamine pyrophosphate (TPP), and lipoic acid (an 8-carbon acid with sulfhydryl groups at positions 6 and 8). The detailed steps of these reactions are shown in Fig. 12-7. 

Cofactors. Many enzymes require relatively loosely bound organic cofactors (coenzymes) or metal ions for activity. A biochemist must be alert for indications of such a requirement during purification of an enzyme, because it may be necessary to add such cofactors to the assay solution to obtain enzyme activity. The interactions of coenzyme with enzyme can be analyzed by kinetic and spectral techniques. Similar techniques are used to evaluate interactions with metal ions. 

Many enzymes require cofactors. When such cofactors are metal ions (e.g. Cu2+, Zn2+, Ni2+, Fe2+/Fe3+) the enzymes are called metalloenzymes. When organic cofactors (coenzymes) are required the coenzyme may be free or tightly bound to the enzyme (as a so-called prosthetic group ). The enzyme-cofactor complex is termed the holoenzyme and the enzyme free of cofactor or coenzyme is called the apoenzyme . 

Examples of some cofactors (coenzymes) frequently used in biocatalytic oxidation reactions and enzymes using these cofactors... 

The range of functionality provided by the 20 amino acids found in proteins consists of weak acids and bases, nucleophiles, hydrogen bond donors and acceptors, and the redox active thiol/disulfide. This limited range of chemistry is inadequate for the catalysis of many reactions found to occur in biological systems. Therefore, a variety of small organic molecules, called cofactors, coenzymes, or vitamins, have evolved to broaden the limited range of chemistry that can be catalyzed by simple proteins. 

Amino acids and peptides, Proteins Enzymes DNA and RNA, Carotenoids, Carbohydrates, Steroids, and Miscellaneous compounds which include Biochemical reagents. Cofactors, Coenzymes and Vitamins are collected in the separate respective sections in this chapter. 

QUESTION 6.8 Identify each of the following as a cofactor, coenzyme, apoenzyme, or holoenzyme ... 

Although a few enzymes have naturally occurring chromophoric substrates, most enzymes do not require a chromophoric cofactor, coenzyme, or substrate for catalysis. If RSSF spectroscopy is to be of use in the study of enzyme systems that lack a natural chromophoric signal, then... 

Formation of an active enzyme (Section 10.3) apoenzyme + cofactor (coenzyme or inorganic ion) —> active enzyme Reaction 10.4... 

The majority of enzymes are based on complex high-molecular-weight proteins, many of which need organic cofactors (coenzymes) if they are to work efficiently. Others need metallic cofactors, either bound to the enzyme by covalent bonds or forming an integral part of the molecule. Others do not bind to the molecule but bind to the primary substrate. 

In the metabolism of carbohydrates, thiamin diphosphate is needed in the conversion of pyruvic acid and the sub uent formation of acetyl coenzyme A, which in turn enters the Krebs cycle and produces vital energy. This is one of the most complex and important reactions in carbohydrate metabolism. In addition to thiamin diphosphate, it also requires the following cofactors coenzyme A, which contains pantothenic acid, nicotinamide adenine dinucleotide (NAD), which contains niacin magnesium ions and lipoic acid. 

These simple examples illustrate that many of the basic active site chemistry of enzymes can be reproduced with simple organic models in the absence of proteins. The role of the latter is of substrate recognition and orientation and the chemistry is often carried out by cofactors (coenzymes) which also have to be specifically recognized by the protein or enzyme. The last chapter of this book is devoted to the chemistry of coenzyme function and design. 

Some ten years ago Dorfman, Berkman, and Koser and Hills showed that pantothenate deficiency reduced the rate of pyruvate metabolism of Proteus morganii and concluded that pantothenate is required in the process of pyruvate oxidation. More recently it has become clear that pantothenate acts in the form of coenzyme A. Korkes, del Campillo, Gunsalus, and Ochoa and Schweet found that the conversion of pyruvate into acetate and CO2 requires, among other cofactors, coenzyme A and DPN. This holds for animal tissues and for bacteria. Lynen and Reichert proposed the mechanism shown in Scheme 7 for the action... 

CO2 to CH4 and extract the resulting free energy via the Wolfe cycle. In the last step, methylcoenzyme M, 16.17, is hydrogenolyzed to methane by a thiol cofactor, coenzyme B, HS-CoB, catalyzed by the Ni enzyme, methylCoM reductase, MCR. 

TABLE 5.1 List of Cofactor/Coenzyme Names and Abbreviations... 

---