Fatty acid synthase complex

The Fatty Acid Synthase Complex Is a Polypeptide Containing Seven Enzyme Activities... 

The Fatty Acid Synthase Complex Acetyl-CoA Carboxylase Are Adaptive Enzymes... 

Figure 11.5 Reactions of the fatty acid synthase complex. A single multi-subunit enzyme is responsible for the conversion of acetyl-CoA to palmitate. The subunits in the enzyme are (i) acetyltransferase, (ii) malonyltransferase, (iii) oxoacyl synthase, (iv) oxoacyl reductase, (v) hydroxyacyl dehydratase, (vi) enoyl reductase. Finally, a separate enzyme, thioester hydrolase, hydrolyses palmitoyl-CoA to produce palmitate (vii).

The Fatty Acid Synthase Complex Has Seven Different Active Sites... 

TABLE 21-1 Proteins of the Fatty Acid Synthase Complex of coli... 

FIGURE 21-5 Sequence of events during synthesis of a fatty acid. The fatty acid synthase complex is shown schematically. Each segment of the disk represents one of the six enzymatic activities of the complex. At the center is acyl carrier protein (ACP), with its phosphopantetheine arm ending in an —SH. The enzyme shown in blue is the one that will act in the next step. As in Figure 21-3, the initial acetyl group is shaded yellow, C-1 and C-2 of malonate are shaded pink, and the carbon released as C02 is shaded green. Steps (T) to (7) are described in the text. 

Synthesis of palmitate (16 0) by the fatty acid synthase complex. [Note Numbers in brackets correspond to bracketed numbers in the text. A second repetition of the steps is indicated by numbers with an asterisk ( ). Carbons provided directly by acetyl CoA are shown in red.]... 

Overview Fatty acid synthesis involves the condensation of two-carbon units, in the form of acetyl CoA, to form long hydrocarbon chains in a series of reactions. These reactions are carried out on the fatty acid synthase complex using NADPH as reductant. The fatty acids are covalently linked to acyl carrier protein (ACP) during their synthesis. 

In prokaryotes, each of the reactions of fatty acid synthesis is catalyzed by a separate enzyme. However, in eukaryotes, the enzymes of the fatty acid synthesis elongation cycle are present in a single polypeptide chain, multifunctional enzyme complex, called fatty acid synthase. The fatty acid synthase complex exists as a dimer, with the ACP moiety shuttling the fatty acyl chain between successive catalytic sites, and from one subunit of the dimer to the other. It is, in effect, a highly efficient production line for fatty acid biosynthesis. 

The (R)-enzyme (molecular mass 800000) was shown to be identical with a subunit of the fatty acid synthase complex. It reduced 3-oxoacid esters specifically to (R)-hydroxyacid esters. K -values for ethyl 3-oxobutanoate and ethyl 3-oxohexanoate were determined as 17.0 mM and 2.0 mM, respectively. Intact fatty acid synthase showed no activity in catalyzing the reduction of 3-oxoacid esters. 

Elongation by the fatty acid synthase complex stops on formation ofpalmitate ( 55). Further elongation and the insertion of double bonds are carried out by other enzyme systems. 

The most important functions of pantothenic acid are its incorporation in coenzyme A and acyl carrier protein (AGP). Both CoA and AGP/4-phosphopantetheine function metabolically as carriers of acyl groups. Coenzyme A forms high-eneigy thioester bonds with carboxylic acids. The most important coenzyme is acetyl CoA. Acetic acid is produced during the metabolism of fatty acids, amino acids, or carbohydrates. The active acetate group of acetyl CoA can enter the Krebs cycle and is used in the synthesis of fatty acids or cholesterol. AGP is a component of the fatty acid synthase multienzyme complex. This complex catalyzes several reactions of fatty acid synthesis (condensation and reduction). The nature of the fatty acid synthase complex varies considerably among different species (91). 

The de novo synthesis of fatty acids from acetyl CoA occurs in the cytosol on the fatty acid synthase complex. 

The growing fatty acid chain on the fatty acid synthase complex is elongated, two carbons at a time, by the addition of the three-carbon compound, malonyl CoA, which is subsequently decarboxylated. With each two-carbon addition, the growing chain, which initially contains a P-keto group, is reduced in a series of steps that require NADPH. NADPH is produced by the pentose phosphate pathway and by the reaction catalyzed by the malic enzyme. 

Palmitate, the product released by the fatty acid synthase complex, is converted to a series of other fatty acyl CoAs by elongation and desaturation reactions. 

Figure 6-7. Fatty acid synthesis. Malonyl CoA provides the 2-carbon units that are added to the growing fatty acyl chain. The addition and reduction steps are repeated until palmitic acid is produced. P = a phosphopantetheinyl group attached to the fatty acid synthase complex Cys-SH = a cys-teinyl residue.

Which one of the following is a characteristic of the product of the fatty acid synthase complex in the liver ... 

C. Biotin is required for the acetyl CoA carboxylase reaction in which the substrate, acetyl CoA, is carboxylated by the addition of C02 to form malonyl CoA. This reaction occurs in the cytosol. Malonyl CoA provides the 2-carbon units that add to the growing fatty acid chain on the fatty acid synthase complex. As the growing chain is elongated, malonyl CoA is decarboxy-lated. 

B. The synthesis of fatty acids from glucose occurs in the cytosol, except for the mitochondrial reactions in which pyruvate is converted to citrate. Biotin is required for the conversion of pyruvate to oxaloacetate, which combines with acetyl CoA to form citrate. Biotin is also required by acetyl CoA carboxylase. Pantothenic acid is covalently bound to the fatty acid synthase complex as part of a phosphopantetheinyl residue. The growing fatty acid chain is attached to this residue during the sequence of reactions that produce palmitic acid. NADPH, produced by the malic enzyme as well as by the pentose phosphate pathway, provides reducing equivalents. Citrate, not isocitrate, is a key regulatory compound. 

A. The 16-carbon, fully saturated fatty add, palmitate (16 0), is the product of the fatty acid synthase complex. It may be elongated by two carbons to form stearic add (18 0), or it may be oxidized to form palmitoleic acid (16 1,A9). Stearate can be oxidized to oleic acid (18 1,A ). Arachidonic acid (20 4,A5,8 11 14) can be synthesized from the essential fatty acid linoleate (18 2,A9 12). It cannot be produced from palmitate. Fatty acids synthesized in the liver are converted to triacylglycerols, packaged in VLDL, and secreted into the blood. 

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