CoenzymeA

Histone acetyltransferases (HATs) are enzymes that acetylate specific lysine residues in histones through the transfer of an acetyl group from an acetyl-coenzymeA (AcCoA) molecule, causing profound effects on chromatin structure and assembly as well as gene transcription. HATs are found in most, if not all, eukaryotic organisms as multiprotein complexes, some HAT catalytic subunits even being shared between various complexes that display different substrate specificities based on their subunit composition [12]. Despite their name, HATs do not restrict themselves to the acetylation of histones, since these enzymes have also been shown to act on nonhistone proteins, broadening their scope of action [13]. 

Figure 2.2 Structures of CcnS histone acetyltransferase (HAT) bound to coenzymeA and various peptides. Schematic representation of Tetrahymena thermophiia CcnS HAT domain (ribbon representation) bound to coenzymeA and 19mers (both shown as ball and sticks) from (a) histone H3 (PDB code lpu9),...

Hoffman L, Besseau S, Geoffroy P, Ritzenthaler C, Meyer D, Lapierre C, Pollet B, Legrand M. 2004. Silencing of hydroxycinnamoyl-coenzymeA shikimate/quinate hydroxycinnomyoltransferase affects phenylpropanoid biosynthesis. Plant Cell 16 1446-1465. 

A familiar example of this type of metabolite adaptation is the thiol ester derivative of acetic acid, acetyl-coenzymeA (acetylCoA). AcetylCoA has a much larger negative free energy of hydrolysis than acetate, so metabolic transformations involving the acetate ion can occur with much lower concentrations of acetylCoA than of acetate. Phosphorylated metabolic intermediates likewise allow metabolites to have high chemical potentials and occur at relatively low concentrations in the cellular water. Use of such activated intermediates enables the cell to avoid high concentrations of metabolites that can tax solvent capacity and, perhaps more important, disrupt the cell through uncontrolled chemical reactions with inappropriate molecules. 

Fig. 4 Reconstruction of the carotenoids biosynthetic pathway in S. cerevisiae. Heterologous activities t-HMGl 3 hydroxy-3-methylglutaryl-coenzymeA, ctrE geranylgeranyldiphosphate synthase (from Xanthophyllomyces dendrorhous), Ctrl phytoene desaturase, ctrYB bifunctional enzyme phytoene synthase and lycopene cyclase. Endogenous yeast activities ISIS I geranylgeranyldiphosphate synthase. Metabolites IPP isopentenyl diphosphate, GPP geranyl diphosphate, FPP famesyl-diphosphate, GGPP geranylgeranyl diphosphate...

Fig. 14. Proposed pathway of maltose and of pyruvate fermentation to acetate, H2 and CO2 in Pyrococcus furiosus. Fdox, oxidized ferredoxin Fdred, reduced ferredoxin CoA, coenzymeA. Numbers in circles refer to enzymes involved (1) Q-glucosidase [296] (2) glucoserferredoxin oxidoreductase (3) gluconate dehydratase (this enzyme has not been detected so far in Pyrococcus furiosus) (4) 2-keto-3-deoxygluconate aldolase (5) glyceraldehyde ferredoxin oxidoreductase (6) glycerate kinase (2-phosphoglycerate forming) (7) enolase (8) pyruvate kinase (9) pyruvateiferredoxin oxidoreductase (10) ADP-forming acetyl-CoA synthetase (11)...

FIGURE 21-3. Biosynthetic pathway for cholesterol. The rate-limiting enzyme in this pathway is 3-hydroxy-3-methylglutaryl coenzymeA reductase (HMG-CoA reductase). 

Bakg + Bqaa- Abbreviations T, activity of the citric acid dele P, activity of the oxidative pentose phosphate pathway Glc6P, glucose 6-phosphate Fru6P, fructose-6-phosphate Gra3P, glyceraldehyde 3-phosphate PEP, phosphoenolpyruvate PYR, pyruvate AcCoA, acetyl coenzymeA OAA, oxaloacetate, AKG, 2-oxoglutarate... 

RNA/(-)RNA plus/minus (sense and antisense) RNA strands AcylCoA acyl coenzymeA ADP adenosine diphosphate DDAB didodecyl dimethyl ammoninm bromide DMPC l,2-dimyristoyl-OT-glycero-3-phosphatidylcholine DNA deoxynncleic acid dNTPs deoxynncleotide triphosphates DOH 1-decanol... 

Matsubara, Y, Indo, Y, Naito, E., Ozasa, H., Glassberg, R., Vockley, J., Ikeda, Y, Kraus, J. Tanaka, K. (1989) J. Biol. Chem. 264, 16321—16331. Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzymeA, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases. Sequence homology of four enzymes of the acyl-CoA dehydrogenase family. 

Scheme 6. Biosynthesis of the quinolizidine alkaloids (+ )-4-coumaroylepilupinine and (-)-13a-tigloyloxymultiflorine. Molecular clones have been isolated for the enzymes shown. Abbreviations ECT,/7-coumaroyl-coenzymeA ( + )-epilupinine 0-/ -coumaroyltransferase HMT/HLT, tigloyl-coenzymeA (-)-13a-hydroxymultiflorine/( +)-13a-hydroxylupanine 0-tigloyltransferase LDC, lysine decarboxylase.

Athappilly FK, Hendrickson WA (1995) Structure of the biotinyl domain of acetyl-coenzymeA carboxylase determined by MAD phasing. Structure 3 1407-19... 

SCoA SCoA acetyl-CoenzymeA aoetyl-CoenzymeA... 

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