Other Cofactors

Other Cofactors.—NAD+ which has been attached to glass by a diazo-coupling procedure probably through C-8 of the adenine ring  

Thiamine pyrophosphate is formed by the direct transfer of a pyro-phosphoryl group from ATP to thiamine. This reaction is unusual as it is one of the few examples of a pyrophosphoryl group being transferred from ATP in one step. Enzyme systems which will catalyse the formation of thiamine pyrophosphate from thiamine in two stages have now been detected in E. coli and yeast. The phosphorylation reactions appear to follow a more usual course and thiamine monophosphate is an intermediate in a two-stage reaction. 

Nishino, A. Iwashima, and Y. Nose, Biochem. Biophys. Res. Comm., 1971, 45, 363. A. Iwashima, H. Nishino, and Y. Nose, Biochim. Biophys. Acta, 1972, 258, 333. 

Biotin carboxylase, an enzyme which catalyses the carboxylation of biotin in E. coli, will catalyse the transfer of phosphate from carbamyl phosphate (44) to ADP. Carbonyl phosphate (45), but not acetyl phosphate, can replace (44) in this system, and this has been taken to imply that the carboxylation of biotin is not a concerted reaction but that (45) is an intermediate in this process. 

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It is considered that the transition from d to d completely removes the fast motion with eigenfrequencies of H0 peculiar to the former, leaving behind only slow decay with relaxation time equal to or greater than V Since the other cofactor in the integrand of Eq. (4.26), M(t), decays much more rapidly (with time tc [Pg.139]

Fig.1. Differentiation ofT cells content of micromilieu and several cytokines and other cofactors released from DCs are essential for the differentiation of naive T cells into T-helper(Th)l,Th2,Th9,Thl7 effectorT-cell subsets. 

Hydrocarbon formation involves the removal of one carbon from an acyl-CoA to produce a one carbon shorter hydrocarbon. The mechanism behind this transformation is controversial. It has been suggested that it is either a decarbonylation or a decarboxylation reaction. The decarbonylation reaction involves reduction to an aldehyde intermediate and then decarbonylation to the hydrocarbon and releasing carbon monoxide without the requirement of oxygen or other cofactors [88,89]. In contrast, other work has shown that acyl-CoA is reduced to an aldehyde intermediate and then decarboxylated to the hydrocarbon, releasing carbon dioxide [90]. This reaction requires oxygen and NADPH and is apparently catalyzed by a cytochrome P450 [91]. Whether or not a decarbonylation reaction or a decarboxylation reaction produces hydrocarbons in insects awaits further research on the specific enzymes involved. 

The transactivation domains only make their accessibility evident in the dimer bound to the HRE. It is very probable that, in this way, the spatial structure (tertiary) optimizes itself so that the contact surfaces between the receptor and the other cofactors of transcription are formed. 

Hydride-transfer reactions involving other cofactors 64 Hydrogen-atom transfer reactions 67 Proton-transfer reactions 69 Experimental signatures of tunneling 70... 

HYDRIDE-TRANSFER REACTIONS INVOLVING OTHER COFACTORS... 

Distinct coenzymes are required in biological systems because both catabolic and anabolic pathways may exist within a single compartment of a cell. The nicotinamide coenzymes catalyze direct hydride transfer (from NAD(P)H or to NAD(P)+) to or from a substrate or other cofactors active in oxidation-reduction pathways, thus acting as two-electron carriers. Chemical models have provided... 

Why did nature use an Fe-S cluster to catalyze this reaction, when an enzyme such as fumarase can catalyze the same type of chemistry in the absence of any metals or other cofactors One speculation would be that since aconitase must catalyze both hydrations and dehydrations, and bind substrate in two orientations, Fe in the comer of a cubane cluster may provide the proper coordination geometry and electronics to do all of these reactions. Another possibility is that the cluster interconversion is utilized in vivo to regulate enzyme activity, and thus, help control cellular levels of citrate. A third, but less likely, explanation is that during evolution an ancestral Fe-S protein, whose primary function was electron transfer, gained the ability to catalyze the aconitase reaction through random mutation. 

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. 

The reduction in enzymatic activity that results from the formation of nonproductive enzyme complexes at high substrate concentration. The most straightforward explanation for substrate inhibition is that a second set of lower affinity binding sites exists for a substrate, and occupancy of these sites ties up the enzyme in nonproductive or catalytically inefficient forms. Other explanations include (a) the removal of an essential active site metal ion or other cofactor from the enzyme by high concentrations of substrate, (b) an excess of unchelated substrate (such as ATP" , relative to the metal ion-substrate complex (such as CaATP or MgATP ) which is the true substrate and (c) the binding of a second molecule of substrate at a subsite of the normally occupied substrate binding pocket, such that neither substrate molecule can attain the catalytically active conformation". For multisubstrate enzymes, nonproductive dead-end complexes can also result in substrate inhibition in the presence of one of the reaction... 

Copper in proteins is not usually accompanied by any other cofactors such as hemes or inorganic sulfur in iron-containing proteins, so that the... 

Fe S-containing enzymes frequently have other redox-active prosthetic groups, notably, flavins FAD or FMN. Likewise, the redox partner for many Fe S proteins is a flavoprotein this provides a convenient mechanism for turning a one-electron transfer reaction into a two-electron donor/acceptor. Hence, the structures elucidating the interactions between Fe S clusters and other cofactors are of considerable interest. At present there are only two examples for which we have crystallographic structures, yet both provide a basis to propose possible mechanisms for electron transfer to Fe S clusters. 

The major secondary events are changes in membrane structure and permeability, changes in the cytoskeleton, mitochondrial damage, depletion of ATP and other cofactors, changes in Ca2+ concentration, DNA damage and poly ADP-ribosylation, lysosomal destabilization, stimulation of apoptosis, and damage to the endoplasmic reticulum. 

Depletion of other cofactors such as UTP, NADH, and NADPH may also be involved in cell injury either directly or indirectly. Thus, the role of NADPH in maintaining reduced GSH levels means that excessive GSH oxidation such as caused by certain quinines, which undergo redox cycling, may in turn cause NADPH depletion (see below). Alternatively, NADPH may be oxidized if it donates electrons to the foreign compound directly. However, NADPH may be regenerated by inter conversion of NAD+ to NADP+. Some quinones such as menadione, l,2-dibromo-3-chloropropane (DBCP), and hydrogen peroxide also cause depletion of NAD, but probably by different mechanisms. Thus, with menadione, the depletion may be the result of... 

The enzyme catalyzing the transfer of D-apiose from UDP-apiose to 4, 5-dihydroxyflavon-7-yl /3-D-glucopyranoside is commonly called apiin synthetase.7 Activity is measured by the formation of [14C]apiin from UDP-[U-14C]apiose. Apiin synthetase can be measured by the rapid separation and isolation, by poly(ethylenimine)-paper chromatography, of a product of the reaction, namely, [14C] apiin, from UDP-D-[U-14C]xylose and degradation products of UDP-[U-14C]apiose.31 There are reports of the isolation and purification of apiin synthetase from parsley leaves,31 from cell-suspension cultures of parsley,121 and from foxglove (Digitalis purpurea).31 Apiin synthetase isolated from parsley does not require metal ions, NAD+, or other cofactors, and is soluble. It is inhibited by several heavy metals, but not by tetra-N-... 

The pyruvate carboxylase reaction requires the vitamin biotin (Fig. 16-16), which is the prosthetic group of the enzyme. Biotin plays a key role in many carboxyla-tion reactions. It is a specialized carrier of one-carbon groups in their most oxidized form C02. (The transfer of one-carbon groups in more reduced forms is mediated by other cofactors, notably tetrahydrofolate and 5-adenosylmethionine, as described in Chapter 18.)... 

Enzyme Source Mass (kDa) Subunit composition Other cofactors... 

An interesting observation relating to the possible control of FDP cleavage in chloroplasts has been reported by Buchanan et al. 111). A latent FDPase present in spinach chloroplast extracts was shown to be specifically activated by reduced ferrodoxin. No other cofactors were required, which appeared to distinguish the latent FDPase from the alkaline FDPase studied by other workers. 

The committee recommends that investigators, including CDC, that conduct surveys of biomarkers in the population should routinely collect detailed information about SES, lifestyle, and other cofactors on each subject and routinely present results organized so as to address the question of whether biomarker concentrations vary as a function of each. Epidemiologic analyses of biomarkers in relation to health should routinely include appropriate adjustments for such covariates. 

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