Metabolic transformations cofactors

Two important implications of the reactions described in Equations (5.1) and (5.2) are (i) that redox reactions play an important role in metabolic transformations, with the cofactors nicotinamide adenine dinucleotide (NAD+) acting as electron acceptor in catabolic pathways and nicotinamide adenine dinucleotide phosphate (NADPH) as electron donor in anabolism, and (ii) that energy must be produced by catabolism and used in biosyntheses (almost always in the form of adenosine triphosphate, ATP). 

The antimetabolites discussed so far, are all compounds of relatively small molecular weight. In the majority of cases, they act by competitively inhibiting the metabolic transformations of the analogous normal metabolites which usually are intermediates (precursors) or cofactors in the biosyntheses of nucleic acids and proteins. In some other cases, the inhibitory action of the antimetabolites is a consequence of their incorporation into the macromolecules (see Section 2.3. B) however, also this type of action depends on their... 

Two important implications of the reactions described in Equations (1) and (2) are (i) that redox reactions play an important role in metabolic transformations, with the cofactors nicotinamide adenine dinucleotide (NAD )... 

Galactose, a constituent of the disaccharide lactose found in dairy products, is metabolized by a patiiwav that includes the isomerization of UDP-galactose to UDP-glucose. where UDP = uridylyl diphosphate. The enzyme responsible for the transformation uses NAD+ as cofactor. Propose a mechanism. 

Since many of the transformations undergone by metabolites involve changes in oxidation state, it is understandable that cofactors have been developed to act as electron acceptors/ donors. One of the most important is that based on NAD/NADP. NAD+ can accept what is essentially two electrons and a proton (a hydride ion) from a substrate such as ethanol in a reaction catalysed by alcohol dehydrogenase, to give the oxidized product, acetaldehyde and the reduced cofactor NADH plus a proton (Figure 5.2). Whereas redox reactions on metal centres usually involve only electron transfers, many oxidation/reduction reactions in intermediary metabolism, as in the case above, involve not only electron transfer but... 

Those nucleosides found in the nucleic acids DNA and RNA involve the joining of ribose of deoxyribose to a purine or a pyrimidine base. One such nucleoside is adenosine, in which a nitrogen of adenine is linked to carbon 1 of the pentose, ribose. In this form it is a component of RNA but as a phosphory-lated derivative of adenosine (e.g. ATP), which is a high energy compound, it fulfils an important role in metabolism. The dinucleotides NAD and NADP are two cofactors necessary for many enzymic transformations and these also contain /V-glycosides of ribose phosphate. Other important nucleosides are found... 

Coenzymes are densely functionalized organic cofactors capable of catalyzing numerous diverse chemical reactions. Nature exploits the intrinsic chemical reactivity of these molecules to extend the chemical fimctionaUty of enzymes well beyond the reactivity of the coded amino acids. When these constituents are incorporated via covalent or non-covalent interactions into coenzyme-depen-dent enzymes, the inherent reactivity of the co enzyme is augmented and directed to effect chemical transformations with substrate and product selectivities, rates, and yields that are unachievable by either the protein or coenzyme alone. Thus, coenzymes play a critical role in the execution of a large number of essential metabolic processes. 

Methanopterin (20) is a folate analogue that is isolated from an archae-bacteria, Methanosarcina thermophila, and the bacteria produces methane from CO2 under anaerobic conditions [18-24]. In the methane-producing metabolic process (Scheme 2), tetrahydromethanopterin (21) is known to work as a cofactor for the reduction of the Ci unit. Here, 21 accepts a formyl group that originates from CO2 and transforms it into the formyl... 

The ability to perform even the simplest of muscle movement requires complex coordination of the physical and chemical activities of the tissue. In recent years, nutritionists and exercise physiologists have described how the primary energy sources in food carbohydrates, fats, and proteins are transformed into the universal "currency" of biological energy, ATP. Oxidative metabolism processes the substrates through a cascade of enzymatic events to Insure maximal efficiency in energy conversion. At every level of this conversion, one or more metal ions serve as a cofactor to facilitate these biochemical reactions. The requirement of metals in the production of... 

Genetic and nutritional studies have illustrated the essential nature of copper for normal brain function. Deficiency of copper during the foetal or neonatal period will have adverse effects both on the formation and the maintenance of myelin (Kuo et al., 2001 Lee et al., 2001 Sun et al., 2007 Takeda and Tamana, 2010). In addition, various brain lesions will occur in many brain regions, including the cerebral cortex, olfactory bulb, and corpus striamm. Vascular changes have also been observed. It is also of paramount importance that excessive amounts of copper do not occur in cells, due to redox mediated reactions such that its level within cells must be carefully controlled by regulated transport mechanisms. Copper serves as an essential cofactor for a variety of proteins involved in neurotransmitter synthesis, e.g. dopamine P-hydroxylase, which transforms dopamine to nor-adrenahne, as well as in neuroprotection via the Cu/Zn superoxide dismutase present in the cytosol. Excess free copper is however deleterious for cell metabolism, and therefore intracellular copper concentration is maintained at very low levels, perhaps as low as 10 M. Brain copper homeostasis is still not well understood. 

R—COOH) forming an acyl-CoA thioester (R—CO—S— CoA) as the metabolic intermediate and as a cofactor. The reaction requires ATP and is catalyzed by various acyl-CoA synthetases also known as acyl-CoA Ugases (Table 32.5) of overlapping substrate specificity. The acyl-CoA conjugates thus formed are seldom excreted, but they can be isolated and characterized relatively easily in in vitro studies. In the present context, the interest of acyl-CoA conjugates is then-further transformation by a considerable variety of path-ways22.37,52 54 summarized in Table 32.6. 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

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