Dinucleotides acylation

Step 1 of Figure 29.3 Introduction of a Double Bond The /3-oxidation pathway begins when a fait)7 acid forms a thioester with coenzyme A to give a fatty acyl Co A. Two hydrogen atoms are then removed from C2 and C3 of the fatty acyl CoA by one of a family of acyl-CoA dehydrogenases to yield an a,/3-unsaturated acyl CoA. This kind of oxidation—the introduction of a conjugated double bond into a carbonyl compound—occurs frequently jn biochemical pathways and usually involves the coenzyme flavin adenine dinucleotide (FAD). Reduced FADH2 is the by-product. 

Figure 9.6 Sequence of electron carriers in the electron transfer chain. The positions of entry into the chain from metabolism of glucose, glutamine, fatty acyl-CoA, glycerol 3-phosphate and others that are oxidised by the Krebs cycle are shown. The chain is usually considered to start with NADH and finish with cytochrome oxidase. FMN is flavin mononucleotide FAD is flavin adenine dinucleotide.

Fig. 2.1. Examples from The Energy Hall of Fame. These molecules not only deliver energy, but transfer special groups in the process. Acyl, RCO— ADP, adenosine diphosphate ATP, adenosine triphosphate dUMP deoxyuridine monophosphate FAD, flavin adenine dinucleotide GTP, guanosine triphosphate NADH, nicotinamide adenine dinucleotide NADP, nicotinamide adenine dinucleotide phosphate P, phosphate TMP, thymidine monophosphate UDP, uridine diphosphate UTP, uridine triphosphate.

A saturated acyl CoA is degraded by a recurring sequence of four reactions oxidation by flavin adenine dinucleotide (FAD), hydration, oxidation by NAD+, and thiolysis by CoA (Figure 22.8). The fatty acyl chain is shortened by two carbon atoms as a result of these reactions, and FADH2, NADH, and acetyl CoA are generated. Because oxidation is on... 

The deprotonation and addition of a base to thiazolium salts are combined to produce an acyl carbanion equivalent (an active aldehyde) [363, 364], which is known to play an essential role in catalysis of the thiamine diphosphate (ThDP) coenzyme [365, 366]. The active aldehyde in ThDP dependent enzymes has the ability to mediate an efScient electron transfer to various physiological electron acceptors, such as lipoamide in pyruvate dehydrogenase multienzyme complex [367], flavin adenine dinucleotide (FAD) in pyruvate oxidase [368] and Fc4S4 cluster in pyruvate ferredoxin oxidoreductase [369]. 

Three types of subunit proteins constitute such dehydrogenase complexes (1) a TPP-dependent decarboxylase, which converts the a-keto acid to an a-hydroxyalkyi-TPP complex (2) a transacylase core, which contains lipoyl residues that are acylated by the a-hydroxyalkyl-TPP and (3) a flavin adenine dinucleotide (FAD)-dependent dihy-drolipoyi dehydrogenase, which reoxidizes the reduced Hpoyl... 

Dichlorophenoxy)butyric acid is converted in the presence of ATP into dichlorophenoxybutyryl coenzyme A. This acyl-CoA is converted by the electron acceptor flavine adenine dinucleotide (FAD) into dichlorophenoxycrotonyl-CoA. One carbon atom of the unsaturated bond is hydroxilated and dichlorophenoxy- -hydroxybutyric acid-CoA is formed. In certain plants possessing specific /3-oxidase enzyme systems, -ketobutyric acid-CoA is formed from this intermediate compound by the mediation of NAD and NADH in a reaction catalysed by -hydroxyacyl-CoA dehydrogenase. This compound is decomposed by hydrolysis into 2,4-D and acetyl-CoA. 

Abbreviations FASN, fatty acid synthase ACC, acetyl-CoA-carboxylase ACL, ATP-citrate lyase NADPH, nicotinamide adenine dinucleotide phosphate MAT, malonyl acetyl transferases KS, ketoacyl synthase KR, p-ketoacyl reductase DH, p-hydroxyacyl dehydratase ER, enoyl reductase TE, thioesterase ACP, acyl carrier protein VLCFA, very long chain fatty acids ELOVL, elongation of very long chain fatty acids SCDl, stearoyl-CoA desaturase-1 AMPK, AMP-activated kinase ME, malic enzyme FASKOL, liver-specific deletion of FAS PPARa, Peroxisome Proliferator-Activating Receptor alpha HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA SREBP, sterol response element binding protein SIP, site-one protease S2P, site-two... 

B3, pantothenic acid dinucleotide, essential for oxidative systems and oxygen transport As CoA precursor, necessary for acyl transfers... 

The ACDs constitute a family of flavin-containing enzymes with at least nine members that catalyze the a,/3-oxidation of fatty acyl-CoA thioesters (see Chapter 7.03). Interest in the structure and mechanism of ACDs stems in part from their potential role in diseases such as sudden infant death syndrome. Most ACDs are homotetramers binding one molecule of flavin adenine dinucleotide (FAD) per subunit, and MCAD, from the mitochondrial /3-oxidation pathway, is the most heavily studied family member. Several reviews on the structure and mechanism of the ACDs have appeared, and the reader s attention is drawn to Thorpe and Kim, Kim and Miura, and Ghisla and Thorpe. ... 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

The cytoplasmic pool of plastidially derived acyl-CoAs can in turn serve as substrates for the reactions of TAG assembly, which occur through the catalytic action of membrane-bound enzymes in the ER in a process that involves membrane metabolism (Weselake 2005). The glycerol backbone used for TAG bioassembly is derived from OT-glycerol-S-phosphate (G3P), which is produced from dihydroxyacetone phosphate (DHAP) and reduced nicotinamide adenine dinucleotide (NADH)... 

Nicotinamide adenine dinucleotide, oxidation-reduction flavin adenine dinucleotide, oxidation-reduction coenzyme A, acyl transfer pyridoxal phosphate, transamination biotin, carboxylation lipoic acid, acyl transfer. 

Pantothenic acid dinucleotide (NAD, NADP) Coenzyme A (CoA) Acyl group transfer... 

Figure 11.2 Reaction sequences catalyzed by 2-oxoacid dehydrogenase complex Pyruvate dehydrogenase complex (PDC) and a-ketoglutarate dehydrogenase complex (aKGDC) catalyze the oxidative decarboxylation of pyruvate (R = CH3) and a-ketoglutarate (R = CH2CH2COOH) to Acetyl-CoA and succinyl CoA respectively. Three component enzymes 2-oxoacid (pyruvate/a-ketoglutarate) decarboxylase, lipoate acetyltransferase/succinyltransferase, dihydrolipoate dehydrogenase as well as five cofactors, namely (1) thiamine pyrophosphate (TPP) and its acylated form, (2) lipoamide (LipS2), reduced form and acylated form, (3) flavin adenine dinucleotide (FAD) and its reduced form, (4) nicotinamide adenine dinucleotide (NAD ) and its reduced form, and (5) coenzyme A (CoASH) and its acylated product are involved.

One mechanism that has been proposed to explain the hepatotoxicity of 1,1,2-trichloroethane is the generation of free radical intermediates from reactive metabolites of 1,1,2-trichloroethane (acyl chlorides). Free radicals may stimulate lipid peroxidation which, in turn, may induce liver injury (Albano et al. 1985). However, Klaassen and Plaa (1969) found no evidence of lipid peroxidation in rats given near-lethal doses of 1,1,2-trichloroethane by intraperitoneal injection. Takano and Miyazaki (1982) determined that 1,1,2-trichloroethane inhibits intracellular respiration by blocking the electron transport system from reduced nicotinamide adenine dinucleotide (NADH) to coenzyme Q (CoQ), which would deprive the cell of energy required to phosphorylate adenosine diphosphate (ADP) and thereby lead to depletion of energy stores. 

Fatty acid beta-oxidation is depicted in Fig. 22.2. hi the first step, the acyl-CoA is oxidized by acyl-CoA dehydrogenase removing two hydrogens and transferring them to FAD (flavin adenine dinucleotide) resulting in 2,3-enoyl-CoA. The unsaturated bond is between atoms 2 and 3 on the beta-carbon. There are several different acyl-CoA dehydrogenases, which differ in the chain length specificity of their substrates. Short-chain... 

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