Acetyl coenzyme structure

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

Chemists and biochemists And it convenient to divide the principal organic substances present m cells into four mam groups carbohydrates proteins nucleic acids and lipids Structural differences separate carbo hydrates from proteins and both of these are structurally distinct from nucleic acids Lipids on the other hand are characterized by a physical property their solubility m nonpolar solvents rather than by their structure In this chapter we have examined lipid molecules that share a common biosynthetic origin m that all their carbons are derived from acetic acid (acetate) The form m which acetate occurs m many of these processes is a thioester called acetyl coenzyme A... 

Sulzenbacher, G., Gal, L., Peneff, C., Fassy, F., and Bourne, Y. (2001). Crystal structure of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyl transferase bound to acetyl-coenzyme A reveals a novel active site architecture. J. Biol. Chem. 276, 11844-11851. 

Hegg, E.L. (2004) Unravelling the structure and mechanism of acetyl-coenzyme A synthase, Acc. Chem. Res., 37, 775-783. 

All polyketides use the same general mechanism for chain elongation. Acetyl coenzyme A provides acetate (C2) units, which are condensed by a ketosynthase (KS). This in turn catalyzes condensation of the growing chain onto an acyl carrier protein (ACP), as generalized in Fig. 1.4. Enzymes such as ketoreductase (KR), enoyl reductase (ER), and dehydratase (DH) establish the oxidation state of caibon during translation, imparting structural diversity. Successive translation of each module leads to a chain of the required length that is eventually passed to thioeste-rase (TE), which releases the chain as a free acid or lactone. 

Thioesters are more reactive towards nucleophilic substitution than oxygen esters, and are widely employed in natural biochemical processes because of this property. Coenzyme A is a structurally complex thiol, and functions in the transfer of acetyl groups via its thioester acetyl coenzyme A (acetyl-CoA CH3CO-SC0A). 

Roesler, K.R., Shorrosh, B.S., and Ohlrogge, J.B., Structure and expression of an Arabidopsis acetyl-coenzyme A carboxylase gene. Plant Physiol, 105, 611, 1994. 

RGURE 13-6 Hydrolysis of acetyl-coenzyme A Acetyl-CoA is a thioester with a large, negative, standard free energy of hydrolysis Thioesters contain a sulfur atom in the position occupied by an oxygen atom in oxygen esters. The complete structure of coenzyme A (CoA, or CoASH) is shown in Rgure 8-41. 

A typical example is the synthesis of acetyl coenzyme A (Eq. 12-45). See Fig. 14-1 for the complete structure of - SH group-containing coenzyme A. 

Abbreviation for acetyl coenzyme A (for complete structure, see Figure 26.1)... 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedrally coordinated by a combination of thiolate and sulfide donors. Of the 10 or more structurally characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein rubredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane structures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane structure (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH3 at a MoFe S8 homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

Acetyl coenzyme A synthase of C. thermoaceticum has a (aP)2 dimer-of-dimers structure with subunit molecular masses 78 kDa (a) and 71 kDa (P). Analysis indicated 12 Fe, 14 S, 2 Ni, 1 Zn per ap dimer. CO dehydrogenase activity resides in the P subunit (AcsA). This subunit has 46% identity (75% homology) with the R. rubrum C00S protein and appears to contain cluster C. Cluster A is located at least partially in the a subunit (AcsA) ACS of Methanosarcina barkeri comprises five subunits a, 84-93 kDa P, 63 kDa y, 53 kDa 8, 51 kDa , 20 kDa [141], The CODH activity is associated with the a subunit. 

However, there are a number of other high-energy molecules that are produced in the metabolism of carbohydrates and fats. The first one we ll consider is acetyl coenzyme A (acetyl Co A). The structure of acetyl coenzyme A is given... 

The name acetyl-CoA is an abbreviation for the compound acetyl coenzyme A, which has the structure shown in Fig. 12-1. Coenzyme A has three components ADP with an additional 3 ... 

The chart overleaf shows the molecules of primary metabolism and the connections between them, and needs some explanation. It shows a simplified relationship between the key structures (emphasized in large black type). It shows their origins—from CO2 in the first instance—and picks out some important intermediates. Glucose, pyruvic acid, citric acid, acetyl coenzyme A (Acetyl Co A), and ribose are players on the centre stage of our metabolism and are built into many important molecules. 

Aryloxyphenoxypropanoates and cyclohexanediones are two classes of herbicides that control many monocotyledoneous species. Although these herbicides are structurally very different (Fig. 1), there has been some conjecture that they have a similar mode of action because of their similarity in selectivity and symptomology. This paper describes the experiments that led to the discovery that aryloxyphenoxypropanoate and cyclohexanedione herbicides inhibit acetyl coenzyme A carboxylase (acetyl-coenzyme A bicarbonate ligase [ATP], EC 6.4.1.2) activity in susceptible species (1). In addition, evidence is presented indicating that the inhibition of acetyl coenzyme A carboxylase (ACCase) is well correlated to observed herbicidal activity. Similar, independent findings have recently been reported by two other research groups (2.3). 

Terpenes are composed of isoprenyl (C-,) units and are conveniently grouped as monoter-penes (skeletal basis CI0 = 2X C-,), sesquiterpenes (G13 = 3X C3), diterpenes (C20 = 4X C-,), triterpenes (C3o = 6X C-,) and tetraterpenes (C40 = 8X G-j. The structures of some representative terpenes are shown in the Appendix (Section 3). Terpenes ultimately derive biosynthetically from acetate (C2) via the activated acetyl thioester (CH3—CO—S—X) acetyl-coenzyme A (acetylCoA CH3-CO-S-C0A) as outlined below (enzymes catalysing key steps being indicated in parentheses). 

The glycolysis of glucose proceeds through several steps involving enol intermediates to afford pyruvate, which can be converted into acetyl coenzyme A (acetyl-CoA) to participate in the Krebs cycle. Kinetic and crystal structure studies point to the key role played in enzyme catalysis by the stabilization of such intermediates on binding of enolate to the metal ion(s) of the enzymes. 

In cells, such acylations occur with the sulfur analogue of an ester, called a thioester, having the general structure RCOSR. The most common thioester is called acetyl coenzyme A, often referred to merely as acetyl CoA. 

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