Enzymes acetylation

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). 

Another important enzymatic process in the production of 7-ADCA, for use in the production of semi-synthetic cephalosporins, is the hydrolysis of 7-aminocephalosporanic add (7-ACA) by the enzyme acetyl esterase. This process, again using immobilisation techniques, is illustrated in Figure 6.16. Hie deacylated product can be used, for example, as an intermediate in the production of the important oral cephalosporin cefuroxime. We will return to cephalosporin antibiotics later in this chapter. 

Production of Malonyl-CoA for the Fatty Acid Biosynthesis. Acetyl-CoA serves as a substrate in the production of malonyl-CoA. There are several routes by which acetyl-CoA is supplied to die cytoplasm. One route is the transfer of acetyl residues from the mitochondrial matrix across the mitochondrial membrane into the cyto-plasm. This process resembles a fatty acid transport and is likewise effected with the participation of carnitine and the enzyme acetyl-CoA-camitine transferase. Another route is the production of acetyl-CoA from citrate. Citrate is delivered from the mitochondria and undergoes cleavage in the cytoplasm by the action of the enzyme ATP-citrate lyase ... 

The reaction is catalyzed by the biotin,enzyme acetyl-CoA carboxylase (E-biotin) assisted by Mg2+ ions. This enzyme is a tetramer with a molecular mass of 400 000-500000. 

The key enzymes involved in the biosynthetic pathways of the Type I compounds are the fatty acid synthesis enzymes acetyl-CoA carboxylase and fatty acid synthetase. These enzymes are similar to those that produce the normal fatty acids used by all organisms. The resulting products are palmitic (16 car-... 

Figure 16.5 Effect of malonyl-CoA on the glucose/fatty acid cycle. Malonyl-CoA is an inhibitor of fatty acid oxidation, so that it decreases fatty acid oxidation in muscle and thus facilitates glucose utilisation (See Figure 7.14). Malonyl-CoA is formed from acetyl-CoA via the enzyme acetyl-CoA carboxylase, which is activated by insulin. Insulin therefore has three separate effects to stimulate glucose utilisation in muscle.

Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S. and Verdin, F. (2006) Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proceedings... 

Selected entries from Methods in Enzymology [vol, page(s)] Assay, 1, 611 3, 935-938 63, 33 separation by HPLC, 72, 45 extraction from tissues, 13, 439 formation of, 1, 486, 518, 585 5, 466 free energy of hydrolysis, 1, 694 substrate for the following enzymes [acetyl-coenzyme A acyl carrier protein transacylase, 14, 50 acetyl-coenzyme A carboxylase, 14, 3, 9 acetyl-coenzyme A synthetase, 13, 375 N-acetyltransferase, 17B, 805 aminoacetone... 

Field J, Rosenthal B, Samuelson J (2000) Early lateral transfer of genes encoding malic enzyme, acetyl-CoA synthetase and alcohol dehydrogenases from anaerobic prokaryotes to Entamoeba histolytica. Mol Microbiol 38 446-455... 

Correct answer = D. Malonyl CoA (three carbons) is synthesized from acetyl CoA (two carbons) by the addition of CO2, using the enzyme acetyl CoA carboxylase. Because CO. is subsequently removed during fatty acid synthesis, the radioactive label will not appear at any position in newly synthesized fatty acids. 

Matthews, J.M., J.A.M. Holtum, D.R. Liljegren, B. Furness, and S.B. Powles (1990). Cross-resistance to herbicides in annual ryegrass (Lolium rigidum). 1. Properties of the herbicide target enzymes acetyl-coenzyme A carboxylase and acetolactate synthase. Plant... 

RN Patel, CG McNamee, LJ Szarka. Enantioselective enzymic acetylation of racemic [4-[4a,6P(E)]]-6-[4,4-bis(4-fluorophenyl)-3-(l-methyl-lH-tetrazol-5-yl)-l,3-butadienyl]tetrahydro-4-hydroxy-2H-pyran-2-one. Appl Microbiol Biotechnol 38 56-60, 1992. 

A Abe ACE ACh ADME ADR Ala Arg Asp ATP dATP AUC Adenine Abequose Angiotensin-converting enzyme Acetyl choline Absorption, distribution, metabolism and elimination Adverse drug reaction Alanine Arginine Aspartate Deoxyadenosine triphosphate Adenosine triphosphate Area under the curve... 

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). 

CoA to form malonyl CoA using C02 in the form of bicarbonate HC03 (Fig. 2). This reaction is catalyzed by the enzyme acetyl CoA carboxylase which has biotin as a prosthetic group, a common feature in C02-binding enzymes. One molecule of ATP is hydrolyzed in the reaction, which is irreversible. The elongation steps of fatty acid synthesis all involve intermediates linked to the terminal sulfhydryl group of the phosphopantetheine reactive unit in ACP phosphopantetheine is also the reactive unit in CoA. Therefore, the next steps are the formation of acetyl-ACP and malonyl-ACP by the enzymes acetyl transacylase and malonyl transacylase, respectively (Fig. 2). (For the synthesis of fatty acids with an odd number of carbon atoms the three-carbon propionyl-ACP is the starting point instead of malonyl-ACP.)... 

Malonyl-CoA contains a 3-carbon dicarboxylic acid, malonate, bound to Coenzyme A. Malonate is formed from acetyl-CoA by the addition of CO2 using the biotin cofactor of the enzyme acetyl-CoA carboxylase. 

While quite apparent to us now, it has taken many years to realize that acetyl-P and carbamyl-P could be substrates for the same enzymes. Acetyl-P was considered, for some years, an important intermediate for acetylation. However, no evidence for either its synthesis or its utilization, other than by phosphatase action (26) with animal... 

Biotin, an essential water-soluble B-complex vitamin, is the coenzyme for four human carboxylases (Fig. 12-2) These include the three mitochondrial enzymes pyruvate carboxylase, which converts pyruvate to oxaloacetate and is the initial step of gluconeogenesis propionyl-CoA carboxylase, which catabolizes several branched-chain amino acids and odd-chain fatty acids and 3-methylcrotonyl-CoA carboxylase, which is involved in the catabolism of leucine and the principally cytosolic enzyme, acetyl-CoA carboxylase, which is responsible for the... 

The pathway from acetate to palmitic acid (actually a palmitic acid-acyl carrier protein complex) involves at least nine enzymes acetyl CoA synthetase, acetyl CoA carboxylase, and the seven enzyme fatty acid synthetase complex. We chose first to test the effect of these compounds on acetyl CoA carboxylase (ACCase) activity. There were several reasons to select ACCase as the... 

Etoxazole and flufenoxuron are inhibitors of chitin biosynthesis. Spirodiclofen and spiromesifen are inhibitors of lipid biosynthesis. Spirodiclofen blocks the enzyme acetyl-coenzyme A carboxylase, which allows mites to synthesize important fatty acids. 

One of the major mechanisms known for sarin-induced toxicity is the irreversible inhibition of the enzyme acetyl-eholinesterase (AChE), resulting in central accumulation of acetylcholine (ACh) and overexcitation of cholinergic neurons in sarin exposure related neurotoxicity. Besides this, a range of noncholinergic effects have been observed... 

Acetyl-CoA is formed from CoA and acetate by the enzyme acetyl-CoA synthetase, an ADP-forming ligase. Phosphotrans-acetylase forms acetyl-CoA from CoA and acetyl-phosphate, which in turn is formed from acetate and ATP catalyzed by acetate kinase. Other enzymes that can form acetyl-CoA from CoA and other acetyl group donors include ATP citrate lyase and thiolase. Longer chain acyl-CoA thioesters are typically formed from CoA and a fatty acid catalyzed by ligases generally known as acyl-CoA synthetases. 

The first partial reaction of pyruvate carboxylase, the formation of carboxybiotin, depends on the presence of acetyl CoA. Biotin is not carboxylated unless acetyl CoA is bound to the enzyme. Acetyl CoA has no effect on the second partial reaction. The allosteric activation of pyruvate carboxylase by acetyl CoA is an important physiological control mechanism that will be discussed in Section 17.3.1. 

Figure 16.26. Biotin-Binding Domain of Pyruvate Carboxylase. This likely structure is based on the structure of the homologous domain from the enzyme acetyl CoA carboxylase (Section 22.4.1). The biotin is on a flexible tether, allowing it to move between the ATP-bicarbonate site and the pyruvate site.

CO2-biotin-enzyme + acetyl Co A —> malonylCoA -I- biotin-enzyme This enzyme is also the essential regulatory enzyme for fatty acid metabolism (Section 22,5). 

From the scheme proposed for Tp. acidophilum, there is no net yield of ATP during the oxidation of glucose to pyruvate. As will be discussed later, the citric acid cycle is probably operational and will produce ATP. However, acetate is excreted from this archaebacterium during growth on glucose[15], and we have shown[2,16] that it is generated from acetyl-CoA with the concomitant production of ATP via the enzyme acetyl-CoA synthase (ADP utilising) ... 

Methanothrix activates acetate differently than Methanosarcina, using only one enzyme, acetyl-CoA synthetase ... 

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