Coenzyme catabolism

Nicotinamide is an essential part of two important coenzymes nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ) (Figure 18.19). The reduced forms of these coenzymes are NADH and NADPH. The nieotinamide eoenzymes (also known as pyridine nucleotides) are electron carriers. They play vital roles in a variety of enzyme-catalyzed oxidation-reduction reactions. (NAD is an electron acceptor in oxidative (catabolic) pathways and NADPH is an electron donor in reductive (biosynthetic) pathways.) These reactions involve direct transfer of hydride anion either to NAD(P) or from NAD(P)H. The enzymes that facilitate such... 

Until now we have viewed the TCA cycle as a catabolic process because it oxidizes acetate units to COg and converts the liberated energy to ATP and reduced coenzymes. The TCA cycle is, after all, the end point for breakdown of food materials, at least in terms of carbon turnover. However, as shown in Figure 20.22, four-, five-, and six-carbon species produced in the TCA cycle also fuel avariety of biosynthetic processes. a-Ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate are all precursors of important cellular species. (In order to par-... 

Vnother pathway of glucose catabolism, the pentose phosphate pathway, is the primary source of N/ E)PH, the reduced coenzyme essential to most reductive biosynthetic processes. For example, N/VDPH is crucial to the biosynthesis of... 

The next three steps—reduction of the /3-carbonyl group to form a /3-alcohol, followed by dehydration and reduction to saturate the chain (Figure 25.7) — look very similar to the fatty acid degradation pathway in reverse. However, there are two crucial differences between fatty acid biosynthesis and fatty acid oxidation (besides the fact that different enzymes are involved) First, the alcohol formed in the first step has the D configuration rather than the L form seen in catabolism, and, second, the reducing coenzyme is NADPH, although NAD and FAD are the oxidants in the catabolic pathway. 

As a rule, the anabolic pathway by which a substance is made is not the reverse of the catabolic pathway by which the same substance is degraded. The two paths must differ in some respects for both to be energetically favorable. Thus, the y3-oxidation pathway for converting fatty acids into acetyl CoA and the biosynthesis of fatty acids from acetyl CoA are related but are not exact opposites. Differences include the identity of the acvl-group carrier, the stereochemistry of the / -hydroxyacyl reaction intermediate, and the identity of the redox coenzyme. FAD is used to introduce a double bond in jS-oxidalion, while NADPH is used to reduce the double bond in fatty-acid biosynthesis. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs tycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

Lactate, a product of glucose catabolism in oxygen-starved muscles, can be converted into pyruvate by oxidation. What coenzyme do you think is needed Write the equation in the normal biochemical format using a curved arrow. 

Ebert S, P-G Rieger, H-J Knackmuss (1999) Function of coenzyme P420 in aerobic catabolism of 2,4,6-trinitro-phenol and 2,4-dinitrophenol by Nocardiodes simplex FJ2-1 A. J Bacterial 181 2669-2674. 

Schleissner C, ER Olivera, M Eernandez-Valverde, M Luengo (1994) Aerobic catabolism of phenylacetic acid in Pseudomonas putida U biochemical characterization of a specific phenylacetic acid transport system and formal demonstration that phenylacetyl-coenzyme A is a catabolic intermediate. J Bacterial 176 7667-7676. 

Gescher J, W Ismail, E Olgeschlager, W Eisenreich, J Wort, G Fuchs (2006) Aerobic benzoyl-coenzyme A (Co A) catabolic pathway in Azoarcus evansii conversion of ring cleavage product by 3,4-dehydroadipyl-CoA semialdehyde dehydrogenase. J Bacterial 188 2919-2927. 

Introductions to enzyme kinetics and bioenergetics are given with explanations of key terms such as Km and Vmax coenzymes, cofactors and inhibitors typical metabolic reactions free energy exergonic and endergonic reactions, catabolism and anabolism. 

Allosteric regulatory molecules are small molecular weight compounds which may be coenzymes (NAD+, ATP, etc.) or intermediate substrates, possibly generated by enzymes found within the same pathway as the regulated enzyme. Alternatively, the allosteric modulator may be generated within another, perhaps complementary, pathway. For example, a regulator may be stimulatory for a catabolic route and at the same time inhibitory for the opposing anabolic pathway. 

Fatty acid utilized by muscle may arise from storage triglycerides from either adipose tissue depot or from lipid stores within the muscle itself. Lipolysis of adipose triglyceride in response to hormonal stimulation liberates free fatty acids (see Section 9.6.2) which are transported through the bloodstream to the muscle bound to albumin. Because the enzymes of fatty acid oxidation are located within subcellular organelles (peroxisomes and mitochondria), there is also need for transport of the fatty acid within the muscle cell this is achieved by fatty acid binding proteins (FABPs). Finally, the fatty acid molecules must be translocated across the mitochondrial membranes into the matrix where their catabolism occurs. To achieve this transfer, the fatty acids must first be activated by formation of a coenzyme A derivative, fatty acyl CoA, in a reaction catalysed by acyl CoA synthetase. 

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

The flavin-based coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are associated with a wide variety of enzymes that catalyze reactions in critical biosynthetic and catabolic processes (Fig. 16). Unlike other coenzymes, the reactions catalyzed do not conserve specific mechanistic pathways. In each case the apoenzyme serves to steer the course of the reaction through specific interactions with substrate and coenzyme [55]. Nonetheless, there are common features of the interactions of the apoenzymes with the flavin which can be exploited in the design of functional peptides and proteins. 

The nicotinamide coenzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) are associated with a wide variety of enzymes involved in oxidation-reduction reactions (Fig. 21). NADH is typically involved in oxidative catabolic reactions, while NADPH is primarily used in biosynthetic pathways [58]. 

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... 

Taurine (H3N CH2CH2S03 ) is formed as a product of cysteine catabolism and also arises from the oxidation of cyste-amine, which is produced during coenzyme-A degradation. It was given the name taurine because it was first isolated from the bile of the ox, Bos taurus. 

The reaction involves formation of an imine through reaction of ammonia with the ketone, followed by reduction of this imine (see Section 7.7.1). As we noted earlier (see Section 15.1.1), nicotinamide coenzymes may also participate in imine reductions as well as aldehyde/ketone reductions, further emphasizing the imine-carbonyl analogy (see Section 7.7.1). The reverse reaction, removal of ammonia from glutamate, is also of importance in amino acid catabolism. 

The pyridine nucleotides NAD"" and NADP" (1) are widely distributed as coenzymes of dehydrogenases. They transport hydride ions (2e and 1 see p. 32) and always act in soluble form. NAD" transfers reducing equivalents from catabolic pathways to the respiratory chain and thus contributes to energy... 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

The oxidation of aciy lic acid can be rationalized in terms of the endogenous catabolism of propionic acid, in which acrylyl coenzyme A is an intermediate. This pathway is analogous with fatty acid 3-oxidation, common to all species and, unlike the corresponding pathway in plants, does not involve vitamin 8,2. 3-Hydroxypropionic acid has been found as an intennediate in the metabolism of acrylic acid in vitro in rat liver and mitochondria (Finch Frederick, 1992). The CO2 excreted derives from the carboxyl carbon, while carbon atoms 2 and 3 are converted to acetyl coenzyme A, which participates in a variety of reactions. The oxidation of acrylic acid is catalysed by enzymes in a variety of tissues (Black Finch, 1995). In mice, the greatest activity was found in kidney, which was five times more active than liver and 50 times more active than skin (Black et al., 1993). 

An early step in the catabolism of amino acids is the separation of the amino group from the carbon skeleton. In most cases, the amino group is transferred to a-ketoglutarate to form glutamate. This transamination reaction requires the coenzyme pyridoxal phosphate. 

Oxidative phosphorylation produces most of the ATP made in aerobic cells. Complete oxidation of a molecule of glucose to C02 yields 30 or 32 ATP (Table 19-5). By comparison, glycolysis under anaerobic conditions (lactate fermentation) yields only 2 ATP per glucose. Clearly, the evolution of oxidative phosphorylation provided a tremendous increase in the energy efficiency of catabolism. Complete oxidation to C02 of the coenzyme A derivative of palmitate (16 0), which also occurs in the mitochondrial matrix, yields 108 ATP per palmitoyl-... 

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