CHI- C-CH- -CoA ATP ADP+ P Acetvl-CoA Malonyl-CoA + HcO biotin Trans carboXvlase carboxvlase arm side arm O-C Biotin camier Biotin Biotin Biotin O NH Acetyl-CoA carboxylase carner protein catalyzes the two-step carboxylation reaction Transcarboxylase of acetvl-CoA in two S-CoA active sites Acetyl-COA S-CoA Malonyl-CoA
biotin carboxylase Transcarboxylase Acetyl-CoA carboxylase catalyzes the two-step carboxylation reaction of acetyl-CoA in two active sites
3. The acetyl and malony groups are first transferred to two-SH groups of the fatty acid synthase complex o The acetyl group of acetyl-Coa is first transferred to the-sh group of a Cys residue on the B-ketoacyl ACP synthase(Ks)in a reaction catalyzed by acetyl-CoA-ACP transacetylase(AT) o The malonyl group is transferred from malonyl-COA to the-SH group of the 4 -phosphopantetheine covalently attached to a Ser residue of the acyl carrier protein(ACP)
3. The acetyl and malony groups are first transferred to two –SH groups of the fatty acid synthase complex ⚫ The acetyl group of acetyl-CoA is first transferred to the –SH group of a Cys residue on the b-ketoacylACP synthase (KS) in a reaction catalyzed by acetyl-CoA-ACP transacetylase (AT). ⚫ The malonyl group is transferred from malonyl-CoA to the –SH group of the 4`-phosphopantetheine covalently attached to a Ser residue of the acyl carrier protein (ACP)
The acyl carrier protein(ACP)is very similar to CoA (thus can be regarded as macro COA) H H OH CH HS-CH-CH,-N-C-CH--CH-N-C-C-C-CH-0-P-0-CH-Ser-ACP O H CH Phosphopantetheine prosthetic group of ACP H OH CH3 Hs-CH2CH2N-C—CH2CH C-C-C-CH-0- 0-CH2O、 Adenine O H CH Phosphopantetheine group of coenzyme A 2-0,PO OH
The acyl carrier protein (ACP) is very similar to CoA (thus can be regarded as “macro CoA”)
Acetyl-CoA CHaC-S CHa ERHD tranalaeatian uf butyryl s-aataacybACPwynthasechs Malonyl-CoA CHI: C CTCHICTS B-Kata HACH Fatty acid synthase ry3-aA-ACP a.kataanLACH yf-ACP 和m|NADP cOg NADPH+ CHiC CHaC CHyCHCHgCts 3.Ketobutyryl-ACP NADPH·H ② ③ a-Hydroxybutyryl-ACP
4. Fatty acids are synthesized by a repeating four-step reaction sequence In th the condensation reaction(step l) catalyzed by B-ketoacyl-ACP synthase, the methylene group of malonyl-CoA (linked to ACP) undergoes a nucleophilic attack on the carbonyl carbon of the acetyl group linked to KS, forming the B-ketobutyryl-ACP with simultaneous elimination of co2 ●theβ- ketobutyryl- aCP is then reduced to d-β hydroxybutyryl-ACP(Step 2), using NADPH and the B-ketobutyryl-ACP reductase(KR)
4. Fatty acids are synthesized by a repeating four-step reaction sequence ⚫ In the condensation reaction (step 1), catalyzed by b-ketoacyl-ACP synthase, the methylene group of malonyl-CoA (linked to ACP) undergoes a nucleophilic attack on the carbonyl carbon of the acetyl group linked to KS, forming the b-ketobutyryl-ACP with simultaneous elimination of CO2 . ⚫ the b-ketobutyryl-ACP is then reduced to D-bhydroxybutyryl-ACP (step 2), using NADPH and the b-ketobutyryl-ACP reductase (KR)