Palmitoyl CoA

Energetic cost of forming palmitoyl-CoA from palmitate and CoA -2 -61... 

Because this enzyme catalyzes the committed step in fatty acid biosynthesis, it is carefully regulated. Palmitoyl-CoA, the final product of fatty acid biosynthesis, shifts the equilibrium toward the inactive protomers, whereas citrate, an important allosteric activator of this enzyme, shifts the equilibrium toward the active polymeric form of the enzyme. Acetyl-CoA carboxylase shows the kinetic behavior of a Monod-Wyman-Changeux V-system allosteric enzyme (Chapter 15). 

Phosphorylation of ACC Modulates Activation by Citrate and Inhibition by Palmitoyl-CoA... 

The regulatory effects of citrate and palmitoyl-CoA are dependent on the phosphorylation state of acetyl-CoA carboxylase. The animal enzyme is phosphorylated at 8 to 10 sites on each enzyme subunit (Figure 25.4). Some of these sites are reg-... 

In the end, seven malonyl-CoA molecules and one acetyl-CoA yield a palmi-tate (shown here as palmitoyl-CoA) ... 

FIGURE 25.25 Biosynthesis of sphingolipids in animals begins with the 3-ketosphinga-nine synthase reaction, a PLP-dependent condensation of palmitoyl-CoA and serine. Subsequent rednction of the keto group, acylation, and desatnration (via rednction of an electron acceptor, X) form ceramide, the precnrsor of other sphingolipids. 

Carefully count and account for each of the atoms and charges in the equations for the synthesis of palmitoyl-CoA, the synthesis of malonyl-CoA, and the overall reaction for the synthesis of palmi-toyl-CoA from acetyl-CoA. 

Long-chain fatty acids (e.g., palmitate Cig) diffuse through pores in the outer mitochondrial membrane, and then form long-chain acyl-CoA esters catalyzed reversibly by palmitoyl-CoA synthase (assumed to be on the inner face of the outer membrane). 

Sphingolipids are biosynthesized by adding head groups to the ceramide moiety. Sphinganine, also termed dihy-drosphingosine, is biosynthesized by a decarboxylating condensation of serine with palmitoyl-CoA to form a keto intermediate, which is then reduced by NADPH (Fig. 3-9). 

Scheme 1. Posttranslational modification of Ras protein with lipid groups (FPP Farnesyl-pyrophosphate, PalCoA Palmitoyl CoA)...

The fatty acid synthesis pathway can be seen to occur in two parts. An initial priming stage in which acetyl-CoA is converted to malonyl-CoA by a carboxylation reaction (Figure 6.9) is followed by a series of reactions which occur on a multi-enzyme complex (MEC), which achieves chain elongation forming C16 palmitoyl-CoA. The whole process occurs in the cytosol. 

After each sequence of reactions the acyl group (C4 after one cycle, C6 after two cycles, C8 after three cycles, etc.) re-enters the process at step 3 and undergoes condensation with the next malonyl-CoA. When the final C16 palmitate molecule has been synthesized it is released but needs to be re-activated with CoA, to palmitoyl-CoA for desaturation, elongation into C18 fatty acid molecule or use for triglyceride synthesis (see Figures 6.12, 6.13 and 6.17). 

The FAS multi-enzyme complex synthesizes saturated C16 fatty acids, but cells and tissues need unsaturated and longer chain fatty acids. The palmitoyl-CoA can be modified by either chain elongation and/or oxidation in order to produce different fatty acid molecules. Both elongation and desaturation occur within the smooth endoplasmic reticulum (SER, microsomal fraction) of the cell. 

Once in the mitochondrial matrix, acyl-CoA (e.g. palmitoyl-CoA), is degraded by 13-oxidation generating acetyl-CoA for the TCA cycle and reduced coenzymes which supply hydrogen atoms and electrons for oxidative phosphorylation. 

Second, esterases have broad (or even very broad) and overlapping substrate specificities. For example, carboxylesterase (EC 3.1.1.1) also catalyzes reactions characteristic of a number of other hydrolases. The discovery that individual isoenzymes of carboxylesterases may be identical to or closely related to acylglycerol lipase, acylcamitine hydrolase, and palmitoyl-CoA hydrolase (see Sect. 2.4.3) has increased the confusion surrounding esterase classification [59], Many esterases are able to hydrolyze amides, thiolesters,... 

Thiolester hydrolases are present in most tissues and cell compartments. High concentrations are found in liver microsomes and in brown adipose tissue mitochondria and peroxisomes. Several acyl-CoA hydrolases have shown a close relationship to the nonspecific carboxylesterases EC 3.1.1.1. Thus, palmitoyl-CoA hydrolase purified from rat liver microsomes was found to be identical to esterase pI 6.2I6A (ES4 type). An acyl-CoA hydrolase was isolated that showed high similarity to esterase pI 6.1 [74a] [129] [130]. These few examples are further illustrations of the unsatisfying situation of the traditional classification of esterases. 

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