Long-chain fatty acids synthesis

Acetyl-CoA, formed from pyruvate by the action of pyruvate dehydrogenase, is the major building block for long-chain fatty acid synthesis in nonruminants. (In ruminants, acetyl-CoA is derived directly from acetate.)... 

Long-chain fatty acid synthesis is controlled in the short term by allosteric and covalent modification of euTymes and in the long term by changes in gene expression governing rates of synthesis of enzymes. 

Kim KH, Lopez-Casillas F, Bai DH, Luo X, Pape ME. Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J 3 2250-2256, 1989. 

In animals and fungi there is a similar dichotomy. NADPH can be generated by cytosolic malic enzyme which catalyses the reaction malate + NADP+ — pyruvate + COg + NADPH. Cytosolic malate derives from the following successive reactions the pyruvate/ citrate shuttle on the mitochondrial inner membrane takes pyruvate to the mitochondrion in exchange for citrate cytosolic ATP citrate lyase catalyses ATP + citrate + CoA-SH —> acetylCoA (CH3CO-S-C0A) + oxaloacetate and cytosolic malate dehydrogenase, which catalyses NADH + oxaloacetate NAD+ + malate. This scheme provides both acetylCoA and NADPH for subsequent long chain fatty acid synthesis (see section on Fatty acid synthesis ). 

Citrate provides the precursors (acetyl-CoA, NADPH) for fatty acid synthesis and is a positive allosteric modulator of acetyl-CoA carboxylase, which is involved in the initiation of long-chain fatty acid synthesis (Chapter 18). It regulates glycolysis by negative modulation of 6-phosphofructokinase activity (see above). All of the above reactions occur in the cytoplasm, and citrate exits from mitochondria via the tricarboxylate carrier. 

A small proportion of our diet consists of very-long-chain fatty acids (20 or more carbons) or branched-chain fatty acids arising from degradative products of chlorophyll. Very-long-chain fatty acid synthesis also occurs within the body, especially in cells of the brain and nervous system, which incorporate them into the sphin-golipids of myelin. These fatty acids are oxidized by peroxisomal p- and a-oxidation pathways, which are essentially chain-shortening pathways. 

This might be expected since ACP-butyrate Is an Intermediate In long chain fatty acid synthesis, and Is unlikely to Inhibit synthesis, although auto-lnhlbltlon by free butyrate cannot be excluded. In any event It Is most likely that cerulenln and butyrate Inhibit C. albicans germination by different mechanisms. 

Long-Chain Fatty Acid Synthesis from Carbohydrate... 

Until recently little information was available concerning the mechanism of long-chain fatty acid synthesis in adipose tissue. Martin et al. (1961) have isolated and partially purified a soluble enzyme system from rat epi-didymal adipose tissue that synthesizes long-chain fatty acids. When acetyl CoA, malonyl CoA, and reduced triphosphopyridine nucleotide are used as substrates, the major product of the reaction is palmitic acid. 

Ikeda, M., Kanao, Y., Yamanaka, M., Sakuraba, H., Mizutani, Y., et al. (2008) Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. FEES Lett. 582 2435-2440. 

Acetyl-CoA carboxylase catalyzes the ATP-dependent carboxylation of acetyl-CoA in the formation of malonyl-CoA [reaction (1)]. Malonyl-CoA is then condensed to acetyl-CoA in the process of long-chain fatty acid synthesis as shown in reaction (2). 

Macey M J K, Stumpf P K 1968 Fat metabolism in higher plants. 36 Long chain fatty acid synthesis in germinating peas. Plant Physiol 43 1637-1647... 

This is not the place to review in detail the elegant studies in Vagelos laboratory nor those in the laboratories of Lynen and Wakil that led to complete elucidation of the mechanism of long-chain fatty acid synthesis which is depicted in Fig. 2, steps 12-18. Needless to say, for the reasons summarized above, the studies with enzymes from C. kluyveri contributed richly to this effort. 

These results raise two intriguing questions. First, what is different in grasses which makes acetyl-CoA carboxylase susceptible to inhibition Second, the relative insensitivity of very long chain fatty acid synthesis to fluazifop inhibition poses a problem as to the source of malonyl-CoA for the elongation reactions. 

Medium and Long-chain Fatty Acid Synthesis. 455... 

M. Yamada and Q. Usami, Long chain fatty acid synthesis in developing castor bean seeds. IV. The synthetic system in protoplastids. Plant Cell Physiol. 16 879 (1975). 

MEDIUM AND LONG-CHAIN FATTY ACID SYNTHESIS... 

In order to examine the apparently selective inhibition of very long chain fatty acid synthesis in vivo, experiments have been carried out in our laboratories using microsomal fractions these contain endoplasmic reticulum, which is the site of fatty acid elongation (Section 3.2). 

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