● a water molecule is then removed from theβ hydroxybutyryl-acp to produce trans-A2 butenoyl-ACP in a reaction catalyzed by p hydroxybutyryl-ACP dehydratase(step 3) o A further reduction(step 4), also using NadPH. of the carbon-carbon double in tranS-A2-butenoy1-ACP, catalyzed by enoyl ACP reductase produces a saturated acyl on ACP(butyryl-ACP o The butyryl group is then transferred to the Cys-sH group of p-ketoacyl-ACP synthase for another round of four reactions which will extend the chain by two more carbons
⚫ A water molecule is then removed from the bhydroxybutyryl-ACP to produce trans-2 - butenoyl-ACP in a reaction catalyzed by bhydroxybutyryl-ACP dehydratase (step 3). ⚫ A further reduction (step 4), also using NADPH, of the carbon-carbon double in trans-2 -butenoyl-ACP, catalyzed by enoylACP reductase produces a saturated acyl on ACP (butyryl-ACP). ⚫ The butyryl group is then transferred to the Cys –SH group of b-ketoacyl-ACP synthase for another round of four reactions, which will extend the chain by two more carbons
o Seven rounds of the four-step lengthening reactions produces palmitoyl-ACP, which will be hydrolyzed to release a free palmitate o The flexible 4-phosphopantetheine group covalently attached to ACP is believed to act as a switch arm to move the intermediates from one active site to the next on the enzyme complex (i.e., the substrates are channeled) o a total of 7 atp and 1 4 NadPh will be consumed for making one palmitate molecule
⚫ Seven rounds of the four-step lengthening reactions produces palmitoyl-ACP, which will be hydrolyzed to release a free palmitate. ⚫ The flexible 4`-phosphopantetheine group covalently attached to ACP is believed to act as a switch arm to move the intermediates from one active site to the next on the enzyme complex (i.e., the substrates are channeled). ⚫ A total of 7 ATP and 14 NADPH will be consumed for making one palmitate molecule
Table 20-1 Proteins of the fatty acid synthase complex of E coli Role L, Agl carrier protein (ACP) Carries acyl groups in thioester linkage Acetyl-CoA-ACP Transfers acyl group from CoA to Cys transacetylase (AT) residue of Ks dlonyl-CoA-ACP Transfers malonyl group from Coa to transferase (MT) ACP &Ketoacyl-ACP synthase(KS) Condenses acyl and malonyl groups &Ketoacyl-ACP reductase(KR) Reduces B-keto group to B-hydroxy group B-HydroxyacyI-ACP Removes HO from B-hydroxyacyl-ACP, dehydratase(HD) creating double bond Enowl-ACP reductase (ER) Reduces double bond, forming saturated acyl-ACP
5. The seven activities of fatty acid synthesis from different organisms have different level of integration o Each activity resides in a separate polypeptide chain in bacteria and higher plants o The seven activities reside in two separate polypeptide chains, with the synthase present as dodecamers(a6β6) o The seven activities reside in one large polypeptide chain in vertebrates, with the synthase present as dimers
5. The seven activities of fatty acid synthesis from different organisms have different level of integration ⚫ Each activity resides in a separate polypeptide chain in bacteria and higher plants. ⚫ The seven activities reside in two separate polypeptide chains, with the synthase present as dodecamers (a6b 6 ). ⚫ The seven activities reside in one large polypeptide chain in vertebrates, with the synthase present as dimers
KS MT he seven activities Bacteria, Plants Seven activities AT(ACPKR) of fatty acid synthase in seven separate are integrated to polypeptides ER HD ifferent levels in ifferent organisms. KS MT Yeast ACP Seven activities AT KR in two separate polypeptides ER HD KS MT Vertebrates Seven activities AT ACP KR in one large ER HD polypeptide
The seven activities of fatty acid synthase are integrated to different levels in different organisms