Acyl transferases

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

SxxK free-standing penicillin-binding proteins (PBPs) are uncoupled SxxK acyl transferases that work mainly as bacterial wall peptidoglycan-hydrolases and function as auxiliary cell-cycle proteins. They are not essential. 

SxxK (3-lactamases are uncoupled SxxK acyl transferases that work as (3-lactam antibiotic hydrolases. They represent a mechanism of defence of great efficiency. On good (3-lactam substrates, their catalytic centres can turn over 1000 times per second. 

Tocotrienols present in rice bran inhibit the liver microsomal enzyme HMGCoA reductase (Qureshi and Qureshi, 1992), the key enzyme involved in the endogenous synthesis of cholesterol, and this helps to lower the circulating cholesterol. Inhibition of another enzyme, ACAT (Acyl coenzyme A acyl transferase), by y-oryzanol results in lowered LDL-C synthesis and enrichment... 

This reaction has been used in the large-scale preparation of an intermediate in the synthesis of a cholesterol acyl-transferase inhibitor.27... 

DHAP-AT dihydroxyacetone phosphate acyl transferase GGF glial growth factor... 

Aromatic amines 4 are metabolised in vivo by cytochrome P450 mediated oxidation to phenolic and hydroxylamine derivatives 5 and 6. Phase II conjugation of the latter with PAPS or acyl transferase results in formation of the sulfuric or acetic acid esters 7. Nitrogen conjugation to give the A-acetyl analogues is also possible (Scheme l).54 65... 

Raetz, C. R., and Roderick, S. L. (1995). A left-handed parallel beta helix in the structure of UDP-N-acetylglucosamine acyl transferase. Science 270, 997-1000. 

A catalytic effect that may be of the same type as the mimicry of acyl transferase enzymes is reported by Gandour et al. (1978). They describe the rate enhancement of the aminolysis of p-nitrophenyl acetate in the presence of bis(2,6-pyridinyl) crown ethers [328] and [329] in chlorobenzene. The rate of... 

At this point, the acyl-CoA is still in the cytosol of the muscle cell. Entry of the acyl-CoA into the mitochondrial matrix requires two translocase enzymes, carnitine acyl transferase I and carnitine acyl transferase II (CAT I and CAT II), and a carrier molecule called carnitine the carnitine shuttles between the two membranes. The process of transporting fatty acyl-CoA into mitochondria is shown in Figure 7.15. 

Regioselective esterification of the 8-hydroxyl group of accumulated monacolin J, produced using a truncated lovastatin biosynthetic pathway, could provide a viable biocatalytic route to simvastatin. With this aim, Xie and Tang cloned and expressed the acyl transferase LovD from the lovastatin biosynthetic pathway into E. colv, they found... 

Recently, the purification of recombinant protein acyl transferases was published. Future investigations will show whether these biocatalysts may also serve as tools for acylating proteins. Depending on their substrate tolerance the incorporation of non-natural acyl analogues could also be possible. 

The initial acylation at the 1-position of glycerol 3-phosphate is catalysed by glycerol 3-phosphate acyl-transferase-1, abbreviated to GPAT-1. This enzyme is specific for a saturated fatty acid (in the acyl form). 

The third acylation is catalysed by diacylglycerol acyl-transferase (DGAT), which is less specific, so that an unsaturated or saturated fatty acid can be incorporated. The final product is as shown in Figure 11.7. 

DAG diacylglycerol LCAT lecithin-cholesterol acyl transferase... 

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