Other Acyltransferases

While storage in membrane phospholipids is, from the standpoint of signal transduction, a predominant fate of arachidonoyl-CoA, additional pathways do exist. For instance, as shown in Figure 2.3, arachidonoyl-CoA may be converted back to arachidonate by a fatty acyl-CoA hydrolase activity, whose biological roles, if any, remain unknown. Moreover, arachidonoyl-CoA is an acceptable substrate for other acyltransferase activities, and it may therefore be used for the synthesis of cholesterol esters (a reserve supply of cholesterol) and triacylglycerols. Arachidonic acid in... 

Hepatocytes sequester RE and cholesteryl esters by receptor-mediated endocytosis of chylomicron remnants. Substantial RE hydrolysis apparently occurs before engulfing of the remnants by lysosomes. CRBP(I) sequesters the atROH released and allows esterification by LRAT but protects from esterification via other acyltransferases, just like CRBP(II) functions in the intestine. Ultimately, liver stellate cells accumulate most of the RE. CRBP(I) seems necessary for retinoid transfer from hepatocytes to stellate cells because the CRBP(I) null mouse does not accumulate RE in stellate cells. The mechanism of transfer, however, has not been estabhshed. 

All of the other enzymes of the /3-oxidation pathway are located in the mitochondrial matrix. Short-chain fatty acids, as already mentioned, are transported into the matrix as free acids and form the acyl-CoA derivatives there. However, long-chain fatty acyl-CoA derivatives cannot be transported into the matrix directly. These long-chain derivatives must first be converted to acylearnitine derivatives, as shown in Figure 24.9. Carnitine acyltransferase I, located on the outer side of the inner mitochondrial membrane, catalyzes the formation of... 

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

ApoC-I is expressed mainly in liver but also in lung, skin, testis, spleen, neural retina, and RPE. Its multiple functions include the activation of lecithin cholesterol acyltransferase (LCAT) and the inhibition, among others, of lipoprotein and hepatic lipases that hydrolyze triglycerides in particle cores. Notably, both LCAT and lipoprotein lipases are expressed in RPE and choroid (Li et al., 2006). Moreover ApoC-I has been shown to displace ApoE on the VLDL and LDL and thus hinder their binding and uptake via their corresponding receptors (Li et al., 2006). 

The best-known effect of APOE is the regulation of lipid metabolism (see Fig. 10.13). APOE is a constituent of TG-rich chylomicrons, VLDL particles and their remnants, and a subclass of HDL. In addition to its role in the transport of cholesterol and the metabolism of lipoprotein particles, APOE can be involved in many other physiological and pathological processes, including immunoregu-lation, nerve regeneration, activation of lipolytic enzymes (hepatic lipase, lipoprotein lipase, lecithin cholesterol acyltransferase), ligand for several cell receptors, neuronal homeostasis, and tissue repair (488,490). APOE is essential... 

The substrates for capsaicinoid synthase were first defined by Fujiwake et al. [70] to be vanillylamine and 8-methyl-6-nonenoyl CoA. The synthesis of dihydrocapsaicin and the other naturally occurring variants are achieved by condensation of vanillylamine with the respective branched chain acyl, for example, 8-methylnonanoyl-CoA. The gene for capsaicinoid synthase has been linked to an acyltransferase At3 or Punl) cloned by Kim et al. [66] and mapped to the C locus on chromosome 2 [71, 72], Direct biochemical confirmation of capsaicinoid synthase remains to be established. 

This enzyme [EC 2.3.1.76], also referred to as retinol fatty-acyltransferase, catalyzes the reaction of an acyl-CoA derivative with retinol to generate coenzyme A and the retinyl ester. The CoA derivative can be palmi-toyl-CoA or other long-chain fatty-acyl derivatives of coenzyme A. 

A major class of enzymes that catalyze the transfer of a group or moiety from one compound to another. The groups being transferred can be one-carbon units such as methyl, hydroxyhnethyl, carbamoyl, or amidino moieties. Enzymes transferring aldehyde or ketonic groups such as transketolase are members of this class. Other examples include acyltransferases, glycosyltransferases, aminotransferases, phosphotransferases, and sulfotrans-ferases. 

Biosynthesis of Digalloylglucose. Besides the above mentioned acyltransferase, oak leaves also contained a completely different type of acyltransferase that catalyzed the formation of digalloylglucose (41). It became evident that this ester was synthesized by a new reaction mechanism in which / -glucogallin was utilized as both acyl donor and acceptor this conclusion was supported by the isolation of analogous acyltransferases related to other metabolic pathways (cf. Table III). Recent studies (54) have shown, in accordance with previous proposals (5,7,8), that 1,6-O-digalloylglucose was produced by the enzyme, and that the stoichiometry of the reaction... 

Suzuki, H. et al.. Identification and characterization of a novel anthocyanin malonyltransferase from scarlet sage Salvia splendens) flowers an enzyme that is phylogenetically separated from other anthocyanin acyltransferases. Plant J., 38, 994, 2004. 

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

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