Acetyl coenzyme syntheses with

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. 

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]... 

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. 

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. 

Isoniazid interferes with mycolic acid synthesis by inhibiting an enoyl reductase (InhA) which forms part of the fatty acid synthase system in mycobacteria. Mycolic acids are produced by a diversion of the normal fatty acid synthetic pathway in which short-chain (16 carbon) and long-chain (24 carbon) fatty acids are produced by addition of 7 or 11 malonate extension units from malonyl coenzyme A to acetyl coenzyme A. InhA inserts a double bond into the extending fatty acid chain at the 24 carbon stage. The long-chain fatty acids are further extended and condensed to produce the 60-90 carbon (3-hydroxymycolic acids which are important components of the mycobacterial cell wall. Isoniazid is converted inside the mycobacteria to a free radical species by a catalase peroxidase enzyme, KatG. The active free radicals then attack and inhibit the enoyl reductase, InhA, by covalent attachment to the active site. 

LDL takes place by way of specific ceE surface LDL receptors on the adrenal gland surface that internalize the cholesterol moiety, releasing it as substrate for steroidogenesis however, ail steroidogenic cells are capable of de novo synthesis from acetyl coenzyme A. To ensure a continuous supply of free cholesterol for steroid synthesis, lipoprotein cholesterol uptake is coordinated with intracellular cholesterol synthesis and with the mobilization of intracellular cholesteryl ester pools. When the rate of cholesterol uptake exceeds the rate of steroidogenesis, intracellular cholesterol synthesis is suppressed, and cholesterol in excess of cellular needs is esterified and stored for future use. 

Choline acetyltransferase catalyzes the synthesis of ACh—the acetylation of choline with acetyl coenzyme A (Co A). Choline acetyltransferase, like other protein constituents of the neuron, is synthesized within the perikaryon and then is transported along the length of the axon to its terminal. Axonal terminals contain a large number of mitochondria, where acetyl CoA is synthesized. Choline is taken up from the extracellular fluid into the axoplasm by active transport. The synthetic step occurs in the cytosol most of the ACh is then sequestered within synaptic vesicles. Inhibitors of choline acetyltransferase have no therapeutic utility, in part because the uptake of choline, not the activity of the acetyltransferease, is rate-limiting in ACh biosynthesis. 

The direct route of acyl coenzyme A synthesis from a free carboxylic acid is catalysed by a group of nucleoside triphosphate-requiring en mes, collectively known as thiokinases. The general mechanism, as exemplified for acetate activation by acetyl thiokinase, proceeds as follows. The carboxylic acid is first activated by acetyl adenylate formation with the displacement of pyrophosphate from ATP. While the initial reaction is fully reversible, subsequent action of pyrophosphatase drives the reaction... 

It is generally considered that there are three systems of fatty acid synthesis. The first, which is highly active, is centred in the cell cytoplasm and results mainly in the production of palmitate from acetyl-coenzyme A or butyryl-coenzyme A. Nearly all other fatty acids are produced by modification of this acid. The second system occurs chiefly in the endoplasmic reticulum and to a minor extent in the mitochondria. It involves elongation of fatty acid chains by two-carbon addition, with malonyl-CoA as donor. The third system, confined to the endoplasmic reticulum, brings about desaturation of preformed fatty acids. 

In dealing with such a vast domain some decisions concerning the subjects addressed in this short chapter had to be made. Consequently, only selected enzymes containing the transition metals copper, iron, manganese, molybdenum/ tungsten, nickel and the related zinc, will be discussed also, we will consider only X-ray structures of active sites published relatively recently and for which some discussion on the catalytic mechanism is included. Some reference is also made to Co in the context of the correnoid iron sulfur protein that interacts with acetyl Coenzyme A synthase in the synthesis or cleavage of acetyl CoA. With a few exceptions, the protein structure beyond the metal coordination sphere will not be described unless it impinges in the catalytic mechanism. 

With the acetyl-CoA synthetase (ACS EC 6.2.1.1) and the pyruvate dehydrogenase complex (PDC) chloroplasts possess two pathways for the synthesis of acetyl coenzyme A. In the meantime, the physiological levels of acetate and pyruvate in spinach chloroplasts have been estimated by nonaqueous fractionation (Treede et al. 1986) and were found to be 5 fold higher in acetate (0.2-0.6 mM). However, the stromal pool size of acetyl coenzyme A, calculated by the same procedure, proved to be too low (about 20 pM) for comparing determinations of the plastidial acetyl coenzyme A level intermediarily formed from both substrates. Thus, in order to check the physiological relevance of acetate and pyruvate for fatty acid synthesis in chloroplasts, which at present is still controversial (Yamada et al. 1975 Roughan et al. 1978), their incorporation into fatty acids by... 

In the presence of suitable enzymes, which can be prepared from animal tissues or bacteria, acetate becomes reactive, provided that coenzyme A and ATP are present. With these two cofactors and the appropriate enzymes acetate can acetylate sulfanilamide, undergo esterification with choline, or combinefwith oxalacetate to form citrate. Since acetyl coenzyme A is an intermediary in these reactions, one of the main problems concerning the enzymic mechanisms is that of the role of ATP in the synthesis of acetyl coenzyme A. Lynen and Reichert pointed out that it is very unlikely that ATP, acetate, and coenzyme A react together simultaneously, and that the most probable sequence is a primary phosphorylation of coenzyme A by ATP... 

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