Butyryl ACP

The net result of this biosynthetic cycle is the synthesis of a four-carbon unit, a butyryl group, from two smaller building blocks. In the next cycle of the process, this butyryl-ACP condenses with another malonyl-ACP to make a... 

One of the steps in fatty-acid biosynthesis is the dehydration of (i )-3-hydroxy-butyryl ACP to give frans-crotonyl ACP. Does the reaction remove the pro-JR or the pro-5 hydrogen from C2 ... 

Reduction of the double bond yields the saturated, chain-elongated butyryl ACP. 

Subsequent dehydration of /3-hydroxybutyryl ACP by an ElcB reaction in step 7 yields trans-ciotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is reduced by NADPH in step 8 to yield butyryl ACP. The doublebond reduction occurs by conjugate addition of a hydride ion from NADPH to the /S carbon of fraus-crotonyl ACP. In vertebrates, the reduction occurs by an overall syn addition, but other organisms carry out similar chemistry with different stereochemistry. 

In step 8 of fatty-acid biosynthesis (Figure 29.5), reduction of fram-crotonyl ACP gives butyryl ACP. A hydride from NADPH adds to C3 of the crotonyl group from file Re face, and protonation on C2 occurs on the Si face. Is tire reduction a syn addition or an anti addition ... 

Step (4) Reduction of the Double Bond Finally the double bond of 1/rm.s-A2-butenoyl-ACP is reduced (saturated) to form butyryl-ACP by the action of enoyl-ACP reductase (ER) again, NADPH is the electron donor. 

Malonyl-ACP, formed from acetyl-CoA (shuttled out of mitochondria) and C02, condenses with an acetyl bound to the Cys—SH to yield acetoacetyl-ACP, with release of C02. This is followed by reduction to the D-/3-hydroxy derivative, dehydration to the trans-A2-unsaturated acyl-ACP, and reduction to butyryl-ACP. NADPH is the electron donor... 

The pathway The first committed step in fatty acid biosynthesis is the carboxylation of acetyl CoA to form malonyl CoA which is catalyzed by the biotin-containing enzyme acetyl CoA carboxylase. Acetyl CoA and malonyl CoA are then converted into their ACP derivatives. The elongation cycle in fatty acid synthesis involves four reactions condensation of acetyl-ACP and malonyl-ACP to form acetoacetyl-ACP releasing free ACP and C02, then reduction by NADPH to form D-3-hydroxybutyryl-ACP, followed by dehydration to crotonyl-ACP, and finally reduction by NADPH to form butyryl-ACP. Further rounds of elongation add more two-carbon units from malonyl-ACP on to the growing hydrocarbon chain, until the C16 palmitate is formed. Further elongation of fatty acids takes place on the cytosolic surface of the smooth endoplasmic reticulum (SER). 

Reduction of crotonyl-ACP by a second NADPH molecule to give butyryl-ACP (catalyzed by enoyl-ACP reductase). 

This first round of elongation produces the four-carbon butyryl-ACP. The cycle now repeats with malonyl-ACP adding two-carbon units in each cycle to the lengthening acyl-ACP chain. This continues until the 16-carbon palmitoyl-ACP is formed. This molecule is not accepted by the acyl-malonyl-ACP condensing enzyme, and so cannot be elongated further by this process. Instead it is hydrolyzed by a thioesterase to give palmitate and ACP. 

In biological pathways, dehydrations rarely occur with isolated alcohols but instead normally take place on substrates in w luch the -OH is positioned two carbons away from a carbonyl group. In the biosynthesis of fats, for instance, /S-hydroxs butyryl ACP is converted by dehydration to fnz/rs-crotonyl AGP, w hcie AGP is an abbreviation for acyl carrier protein. Wcdl see the reason for this requirement in Section 11.10. 

In the second round of fatty acid synthesis, butyryl ACP condenses with malonyl ACP to form a C5-P-ketoacyl ACP. This reaction is like the one in the first round, in which acetyl ACP condenses with malonyl ACP to form a C4-P-ketoacyl ACP. Reduction, dehydration, and a second reduction convert the C5-P-ketoacyl ACP into a C5-acyl ACP, which is ready for a third round of elongation. The elongation cycles continue until Ci5-acyl ACP is formed. This intermediate is a good substrate for a thioesterase that hydrolyzes C 15-acyl ACP to yield palmitate and ACP. The thioesterase acts as a ruler to determine fatty acid chain length. The synthesis of longer-chain fatty acids is discussed in Section 22.6. 

STEP 7 Dehydration of /3-hydroxy-butyryl ACP yields crotonyl ACP. 

STEP 8 Reduction of crotonyl ACP yields butyryl ACP, the final product of the first elongation cycle. 

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