Acetyl coenzyme A synthesis

The liver meets the larger part (60%) of its requirement for cholesterol by synthesis de novo from acetyl-coenzyme A. Synthesis rate is regulated at the step leading from hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonic acid (p.l61A), with HMG-CoA reductase as the rate-limiting enzyme. 

Barondeau, D. P., and Lindahl, P. A., 1997, Methylation of carbon monoxide dehydrogenase from Clostridium thermoaceticum and mechanism of acetyl coenzyme A synthesis, J. Am. Chem. Soc. 119(17) 3959n3970. 

Harder SR, Lu W-P, Freiberg BA, Ragsdale SW (1989) Spectroelectrochemical studies of corri-noid iron-sulfur protein involved in acetyl coenzyme-A synthesis by Clostridium thermoace-ticum. Biochemistry 28 9080-9087... 

Treede H.J., Riens B. and Heise K.P., 1986. Species-specific differences in acetyl coenzyme A synthesis of chloroplasts. Z. Naturforsch. 41c, 733-740 Uchiyama M., Washio N., Ikar T., Igarashi H. and Suzuki I., 1986. Stereospecific responses to (R)-(+)-and (S)-(-)-quizalofop-ethyl in tissues of several plants. J. Pesticide Sci 459-467. 

REGULATION OF ACETYL COENZYME A SYNTHESIS IN CHLC OPLASTS... 

CODH can bring about two reactions (e.g., Eq. 16.26 and Eq. 16.28) of particular organometallic interest the reduction of atmospheric CO2 to CO (CODH reaction, Eq. 16.26) and acetyl coenzyme A synthesis (ACS reaction, Eq. 16.28) from CO, a CH3 group possibly taken from a corrinoid iron-sulfur protein (denoted CoFeSP in the equation), and coenzyme A, a thiol. Tliese are analogous to reactions we have seen earlier the water-gas shift reaction (Eq. 16.25) and the Monsanto acetic acid process (Eq. 16.27). 

Roberts, J.R., Lu, W.P., Ragsdale, S.W., 1992. Acetyl-coenzyme-A synthesis from methylte-trahydrofolate, CO, and coenzyme-A by enzymes purified from clostridium-thermoaceticum — attainment of invivo rates and identification of rate-limiting steps. Journal of Bacteriology 174 (14), 4667—4676. 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Acetylcholine synthesis and neurotransmission requires normal functioning of two active transport mechanisms. Choline acetyltransferase (ChAT) is the enzyme responsible for ACh synthesis from the precursor molecules acetyl coenzyme A and choline. ChAT is the neurochemical phenotype used to define cholinergic neurons although ChAT is present in cell bodies, it is concentrated in cholinergic terminals. The ability of ChAT to produce ACh is critically dependent on an adequate level of choline. Cholinergic neurons possess a high-affinity choline uptake mechanism referred to as the choline transporter (ChT in Fig. 5.1). The choline transporter can be blocked by the molecule hemicholinium-3. Blockade of the choline transporter by hemicholinium-3 decreases ACh release,... 

Brain ChAT has a KD for choline of approximately 1 mmol/1 and for acetyl coenzyme A (CoA) of approximately 10pmol/l. The activity of the isolated enzyme, assayed in the presence of optimal concentrations of cofactors and substrates, appears far greater than the rate at which choline is converted to ACh in vivo. This suggests that the activity of ChAT is repressed in vivo. Surprisingly, inhibitors of ChAT do not decrease ACh synthesis when used in vivo this may reflect a failure to achieve a sufficient local concentration of inhibitor, but also suggests that this step is not rate-limiting in the synthesis of ACh [18-20]. 

Figure 2.14 Iriter-relationship between intermediary. metabolism of glucose, phospholipids and acetylcholine synthesis. Acetyl CoA acetyl coenzyme A CAT-catechol-O-methyltransferase AChE acetylcholinesterase.

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose 5-phosphate (Figure 21). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthraniUc acid as aromatized CoA ester (antraniloyl-CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate (Figure 21). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline and acridine. 

The biosynthesis of steroids is complex, as one wonld expect since all the compounds in this group must be derived from a single precnrsor (cholesterol (5.4)). The primary sonrce of all the compounds involved in steroid synthesis is acetate, in the form of acetyl-coenzyme A. Cholesterol, besides being ingested in food, is synthesized in large amounts, and an adnlt human contains about 250 g of cholesterol. In contrast, the steroid hormones are produced at the milligram level or lower. 

S ATP -P acetate <1-18> (<8> acetate kinase/phosphotransacetylase, major role of this two-enzyme sequence is to provide acetyl coenzyme A which may participate in fatty acid synthesis, citrate formation and subsequent oxidation [1] <3> function in the metabolism of pyruvate or synthesis of acetyl-CoA coupling with phosphoacetyltransacetylase [15] <11> function in the initial activation of acetate for conversion to methane and CO2 [19] <10> key enzyme and responsible for dephosphorylation of acetyl phosphate with the concomitant production of acetate and ATP [30]) (Reversibility r <1-18> [1, 2, 5-21, 24-27, 29-33]) [1, 2, 5-21, 24-27, 29-33]... 

The synthesis of fatty acids for incorporation into milk fat within the mammary gland is similar to that seen in other tissues. There are two basic reactions the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA, followed by incorporation of the latter into a growing acyl chain via the action of the fatty acid-synthetase complex. However, the product of these reactions in lactating mammary tissue from many species is short and medium chain fatty acids. In most other tissues the product is palmitate. For more complete details see Moore and Christie, (1978), Bauman and Davis (1974), and Patton and Jensen (1976). 

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. 

Acetylcholine synthesis. Acetylcholine (ACh) is a prominent neurotransmitter, which is formed in cholinergic neurons from two precursors, choline and acetyl coenzyme A (AcCoA) (Fig. 12—8). Choline is derived from dietary and intraneuronal sources, and AcCoA is synthesized from glucose in the mitochondria of the neuron. These two substrates interact with the synthetic enzyme choline acetyltransferase to produce the neurotransmitter ACh. 

This is followed by removal of the glutamic acid and the glycine residues, which is followed by acetylation of the remaining cysteine. Essential amino acids are required for the synthesis of the proteins involved, pantothenic acid for coenzyme A synthesis, and phosphorus for synthesis of the ATP needed for glutathione synthesis. Similar scenarios can be developed for glucuronide and sulfate formation, acetylation, and other phase II reaction systems. 

CO to C02 in a similar way to the CODH of photosynthetic bacteria, and also the synthesis of acetyl coenzyme A [140]. 

Acetyl coenzyme A synthase of C. thermoaceticum is able to catalyze the whole reaction for reductive synthesis of acetyl coenzyme A from carbon dioxide, a methylated corrinnoid/iron-sulfur protein, and coenzyme A. The enzyme catalyzes several exchange reactions [147-149] ... 

When cucurbit cells are fed O-acetylserine or its metabolic precursors the rate of hydrogen sulfide emission in response to sulfate declines, and the incorporation of labeled sulfur from 35S-sulfate into cysteine increases (18). Inhibition of the synthesis of the O-acetylserine precursor acetyl coenzyme A by 3-fluoropyruvate (22) enhances hydrogen sulfide emission, but inhibits cysteine synthesis (1 ). These observations indicate that the availability of O-acetylserine is the rate limiting factor in cysteine synthesis. Hydrogen sulfide may be emitted to the extent the amount of sulfate reduced exceeds the synthesis of O-acetylserine. Therefore, direct release of sulfide from carrier-bound sulfide appears to be responsible for the emission of hydrogen sulfide in response to sulfate (Figure 1, pathway 1). 

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