Reduced acyl carrier protein

FAS activity, as assayed m vitro in soluble extracts from plcints, heis long been known to require exogenous, reduced acyl carrier protein (ACP). More recently. 

Figure 13.26 Dioxygen-utilizing carboxylate-bridged diiron centres (a) Oxidized (top) and reduced (bottom) MMOH (b) oxidized (top) and Mnn-reconstituted ToMOH (bottom) (c) oxidized (top) and reduced (bottom) RNR-R2 (d) oxidized (top) and reduced (bottom) rubryerythrin (e) reduced stearoyl-acyl carrier protein A9 desaturase (f) reduced bacterioferritin (g) methaemerythrin. Fel is on the left and Fe2 on the right. (Reprinted with permission from Sazinsky and Lippard, 2006. Copyright (2006) American Chemical Society.)...

At pH 7.0 a similar activation was observed when the enzyme was incubated with reduced CoA or acyl carrier protein. At this lower pH oxidized CoA was ineffective, and the activation was inhibited by anaerobic conditions or by the addition of EDTA. It was concluded that activation at neutral pH was an oxidative reaction catalyzed by traces of Cu2+ present in the reaction mixtures ... 

Conformational changes in diiron center of stearoyl-acyl carrier protein desaturase caused by substrate binding have been probed by EPR and proton ENDOR of cryoreduced diferric protein.80 EPR spectra of the one-electron reduced Fe(III)Fe(II)... 

Fig. 7.1 The FASN Enzyme. A. The FASN polypeptide comprises seven functional domains the ketoacyl synthase (KS), malonyl acetyl transferase (MAT), P-hydroxyacyl dehydratase (DH), enoyl reductase (ER), P-ketoacyl reductase (KR), the acyl carrier protein (ACP), and thioesterase (TE) domains. B. The FASN reaction mechanism. The MAT domain of the enzyme binds malonyl-CoA and acetyl-CoA, while the KS domain acts to condense the growing acyl chain. The resulting P-ketoacyl moiety is then reduced in steps by the KR, DH, and ER to a saturated acyl intermediate. This process is repeated in seven cycles, after which, the TE domain releases the sixteen carbon fatty acid palmitate...

Though the reactions in fatty acid biosynthesis resemble the reversal of the analogous reactions in oxidation, fatty acid synthesis is distinct from fatty acid oxidation (Figure 18.23). For example, acyl groups are carried by acyl carrier protein in fatty acid synthesis, instead of coenzyme A. Furthermore, reducing equivalents come from NADPH and energy is provided by ATP. Overall, the biosynthesis of palmitate from 8 acetyl-CoAs requires 7 ATPs and 14 NADPHs. 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

---