Synthesis of Long-Chain Saturated Fatty Acids

Ethanol is a teratogen partly because it inhibits embryonic cellular proliferation. Maternal alcoholism causes fetal alcohol syndrome, which is characterized by abnormal function of the central nervous system, microcephaly, cleft palate, and micrognathia. 

4 Synthesis of Long-Chain Saturated Fatty Acids 

De novo synthesis takes place in the cytosol (whereas fatty acid oxidation occurs in mitochondria). 

All carbon atoms are derived from acetyl-CoA (obtained from carbohydrates or amino acids), and 

The committed (rate-controlling) step is the biotin-dependent carboxylation of acetyl-CoA by acetyl-CoA carboxylase. Important allosteric effectors are citrate (positive) and long-chain acyl-CoA derivatives (negative). 

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Malic enzyme catalyses the NADP-dependent oxidative decarboxylation of malate to pyruvate and C02 with the production of NADP which is utilized for the synthesis of long chain saturated fatty acids from malonyl CoA. 

SECTION 18.4 Synthesis of Long-Chain Saturated Fatty Acids... 

Synthesis of 22 6n-3 was not impaired in cell lines with X-ALD (Table 2), suggesting that the adrenoleukodystrophy protein (ALDP), a peroxisomal membrane protein that has been hypothesized to transport very-long-chain saturated fatty acids, does not participate in the retroconversion step of 24 6n-3 to 22 6n-3. The biosynthesis of 22 6n-3 was also normal in fibroblasts from patients with Refsum disease, who have a defect in peroxisomal fatty acid a-oxidation, indicating that a-oxidation does not contribute to 22 6n-3 synthesis. 

Chemical synthesis of the palmitoyl- and stearoyl-derivatives of dihydrosphingomyelin confirmed this structure (Shapiro et al. 1958). Long chain saturated fatty acids, mono- and even diunsaturated fatty acids (predominantly stearic, lignoceric and nervonic acids) have been isolated from sphingomyelin, but no hydroxy fatty acids (Sweeley 1963 Kishimoto et al. 1963 O Brien et al. 1964). 

Figure 16.4 Long-chain and very long-chain fatty acid biosynthesis in mammals. The long-chain saturated fatty acids and unsaturated fatty acids of the n-10, n-7, and n-9 families (Top panel) can be synthesized from palmitic acid (Cl6 0) produced by the cellular fatty acid synthesis machinery. Long-chain fatty acids of the n-6 and n-3 famihes can only be synthesized from their respective precursors obtained from diets. The symbols of, , and stand for the involved activities of desaturation, elongation, and peroxisomal 3-oxidation, respectively, in the steps. Many isoforms of the genes corresponding to these activities were identified (see the review [34] for details).

Vegetable oils or fats have also been used as starting materials for the enzymatic synthesis of structured lipids with valuable dietetic or nutritional properties. Milk fat substitutes for use in baby foods have been produced enzymatically from pahn oil mid-fractions (King and Padley, 1990). Using the same enzymatic process, long-chain saturated fatty acids (which have been implicated in atherogenesis) at the sn-2 position of peanut oil triacylglycerols have been replaced with oleic acid (Sridhar et al, 1991). 

Fatty acids are long-chain carboxylic acids. The carboxyl carbon is number 1, and carbon number 2 is referred to as the a carbon. When designating a fatty acid, the number of carbons is given along with the number of double bonds (carbons double bonds). Saturated fatty acids have no double bonds. Palmitic acid (palmitate) is the primary end product of fetty acid synthesis. 

Figure 11.7 Synthesis of triaq/lglyceroL The precursors are glycerol 3-phosphate and long-chain acyl-CoA. R, is a saturated fatty acid, R2 is an unsaturated fatty acid (one or two doubte bonds) and R3 is either saturated or unsaturated. The activity of GPAT-1 regulates triacylglycerol synthesis. In all reactions involving RCO.SCoA, the CoASH is released but is not shown in this diagram. P,- - phosphate.

The composition of the free fatty acids is also unique. In both human and pig stratum cornea, the free fatty acid fraction consists mainly of long and saturated hydrocarbon chains [44,45], Oleic and linoleic acid are the only unsaturated free fatty acids detected in the stratum corneum. There are various sterols present in human stratum corneum, of which cholesterol predominates. Cholesterol is the only major lipid class that is present in both plasma membranes and the intercellular lipid lamellae. Cholesterol is synthesized in the epidermis and this synthesis is independent of the hepatic one. A minor fraction is sulfated to... 

Lipase A seems to be responsible for the interesterification characteristics of the immobilized crude lipase preparation, including its unique specificity towards saturated fatty acids. Further, Lipase A can explain some of the activity found in ester synthesis with long-chain alcohols. On the other hand, Lipase B is responsible for the activity in ester synthesis of short-chain alcohols, and for some of the activity on long-chain alcohols. 

The enzyme system that catalyzes the synthesis of saturated long-chain fatty acids from acetyl CoA, malonyl CoA, and NADPH is called the fatty acid synthase. The constituent enzymes of bacterial fatty acid synthases are dissociated when the cells are broken apart. The availability of these isolated enzymes has facilitated the elucidation of the steps in fatty acid synthesis (Table 22.2). In fact, the reactions leading to fatty acid synthesis in higher organisms are very much like those of bacteria. 

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