Acyl-carrier proteins

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

Using HSCoA and HS—ACP as abbreviations for coenzyme A and acyl carrier protein respectively write a structural formula for the tetrahedral... 

Formation of malonyl coenzyme A is followed by a nucleophilic acyl substitution which transfers the malonyl group to the acyl carrier protein as a thioester... 

When both building block units are m place on the acyl carrier protein carbon-carbon bond formation occurs between the a carbon atom of the malonyl group and the carbonyl carbon of the acetyl group This is shown m step 1 of Figure 26 3 Carbon-carbon bond formation is accompanied by decarboxylation and produces a four carbon acetoacetyl (3 oxobutanoyl) group bound to acyl earner protein... 

Acetyl and malonyl groups bound to acyl carrier protein... 

Biosynthesis of coen2yme A (CoA) ia mammalian cells incorporates pantothenic acid. Coen2yme A, an acyl group carrier, is a cofactor for various en2ymatic reactions and serves as either a hydrogen donor or an acceptor. Pantothenic acid is also a stmctural component of acyl carrier protein (AGP). AGP is an essential component of the fatty acid synthetase complex, and is therefore requited for fatty acid synthesis. Free pantothenic acid is isolated from hver, and is a pale yeUow, viscous, and hygroscopic oil. 

By analogy to the intermediates given in steps 1-4 of Figure 26.3, write the sequence of acyl groups that are attached to the acyl carrier protein in the conversion of... 

Pantothenic acid, sometimes called vitamin B3, is a vitamin that makes up one part of a complex coenzyme called coenzyme A (CoA) (Figure 18.23). Pantothenic acid is also a constituent of acyl carrier proteins. Coenzyme A consists of 3, 5 -adenosine bisphosphate joined to 4-phosphopantetheine in a phosphoric anhydride linkage. Phosphopantetheine in turn consists of three parts /3-mercaptoethylamine linked to /3-alanine, which makes an amide bond with a branched-chain dihydroxy acid. As was the case for the nicotinamide and flavin coenzymes, the adenine nucleotide moiety of CoA acts as a recognition site, increasing the affinity and specificity of CoA binding to its enzymes. 

The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

Intermediates in fatty acid synthesis are linked covalently to the suifhydryl groups of special proteins, the acyl carrier proteins. In contrast, fatty acid breakdown intermediates are bound to the —SH group of coenzyme A. Fatty acid synthesis occurs in the cytosol, whereas fatty acid degradation takes place in mitochondria. 

Acyl Carrier Proteins Carry the Intermediates in Fatty Acid Synthesis... 

FIGURE 25.6 Fatty acids are conjugated both to coenzyme A and to acyl carrier protein through the sulfliydryl of phosphopantetheine prosthetic groups. 

FIGURE 25.7 The pathway of palmhate synthesis from acetyl-CoA and malonyl-CoA. Acetyl and malonyl building blocks are introduced as acyl carrier protein conjugates. Decarboxylation drives the /3-ketoacyl-ACP synthase and results in the addition of two-carbon units to the growing chain. Concentrations of free fatty acids are extremely low in most cells, and newly synthesized fatty acids exist primarily as acyl-CoA esters. 

FIGURE 25.20 Triacylglycerols are formed primarily by the action of acyltransferases on mono- and diacylglycerol. Acyltransferase in E. coli is an integral membrane protein (83 kD) and can utilize either fatty acyl-CoAs or acylated acyl carrier proteins as substrates. It shows a particular preference for palmitoyl groups. Eukaryotic acyltransferases nse only fatty acyl-CoA molecnles as substrates. 

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