Acetyl-isoenzyme

Carbonic anhydrase (CA, also called carbonate dehydratase) is an enzyme found in most human tissues. As well as its renal role in regulating pH homeostasis (described below) CA is required in other tissues to generate bicarbonate needed as a co-substrate for carboxylase enzymes, for example pyruvate carboxylase and acetyl-CoA carboxylase, and some synthase enzymes such as carbamoyl phosphate synthases I and II. At least 12 isoenzymes of CA (CA I—XII) have been identified with molecular masses varying between 29 000 and 58 000 some isoenzymes are found free in the cytosol, others are membrane-bound and two are mitochondrial. 

The first two reactions in the cholesterol synthetic pathway are siri lar to those in the pathway that produces ketone bodies (see Figure 16.22, p. 194). They result in the production of 3-hydroxy-3-methyl-glutaryl CoA (HMG CoA, Figure 18.3). First, two acetyl CtA molecules condense to form acetoacetyl CoA. Next, a third molecule of acetyl CoA is added, producing HMG CoA, a six-carbon compound. [Note Liver parenchymal cells contain two isoenzymes of HMG CoA synthase. The cytosolic enzyme participates in cholesterol synthesis, whereas the mitochondrial enzyme Urc tions in the pathway for ketone body synthesis.]... 

Both bacteria and plants have separate enzymes that catalyze the individual steps in the biosynthetic sequence (Fig. 17-12). The fatty acyl group grows while attached to the small acyl carrier protein (ACP).54 58 Control of the process is provided, in part, by the existence of isoenzyme forms. For example, in E. coli there are three different P-oxoacyl-ACP synthases. They carry out the transfer of any acyl primer from ACP to the enzyme, decarboxylate malonyl-ACP, and carry out the Claisen condensation (steps b, e, and/in Eq. 17-12)58a e One of the isoenzymes is specialized for the initial elongation of acetyl-ACP and also provides feedback regulation.58c The other two function specifically in synthesis of unsaturated fatty acids. 

Two molecules of acetyl CoA condense to produce acetoacetyl CoA. This reaction is catalyzed by thiolase or an isoenzyme of thiolase. 

CYP = cytochrome P450 isoenzyme NAT = N-acetyltransferase P-CP = P-glycoprotein PM, glue = phase II glucuronidation. PMs = poor metabolizers EMs = extensive metabolizers SAs = slow acetylators FAs = fast acetylators. 

Jin T, Nordberg GF, Wu X, Ye T, Kong Q, Wang Z, Zhuang F and Cal S. Urinary N-Acetyl- 3-D-glucosaminidase isoenzymes as biomarker of renal dysfunction caused by cadmium in a general population. Environ Res Sect A 1999 81 167-173. 

Rustom R, Costigan M, Shenkin A, Bone JM. Proteinuria and renal tubular damage urinary N-acetyl- 3-D-glucosaminidase and isoenzymes in dissimilar renal disease. Am J Nephrol 1998 18 179-185. 

Ampholyte displacement chromatography [43] does not require special packings to be applied. Conventional ion exchangers are sufficient. The main principle is the elution of the column with carrier ampholytes. Leaback and Robinson [43] used CM-cellulose for separation of acetyl hexosamidase isoenzymes (Fig. 4.5.3), Young and Webb [44,50] separated serum proteins on DEAE-cellulose, and Chapuis-Cellier et al. [97] described ampholyte displacement chromatography of hemoglobins on DEAE-cellulose. 

Morita, A., Y. Numata, Y. Kosigi, A. Noto, N. Takeuchi, and K. Uchida. 1998. Stabilities of N-acetyl-p-D-glucoaminidase isoenzymes Advantage of NAG isoenzyme B measurement in clinical applications. Clinica ChimicaActa 278 35 3. 

Fig. 22.12. Major sites of regulation in the glycolytic pathway. Hexokinase and phos-phofructokinase-1 are the major regulatory enzymes in skeletal muscle. The activity of pyruvate dehydrogenase in the mitochondrion determines whether pyruvate is converted to lactate or to acetyl Co A. The regulation shown for pyruvate kinase only occurs for the liver (L) isoenzyme.

Between meals, a decreased insulin level and increased levels of insulin counter-regulatory hormones (e.g., glucagon) activate hpolysis, and free fatty acids are transported to tissues bound to serum albumin. Within tissnes, energy is derived from oxidation of fatty acids to acetyl CoA in the pathway of -oxidation. Most of the enzymes involved in fatty acid oxidation are present as 2-3 isoenzymes, which have different but overlapping specificities for the chain length of the fatty acid. Metabolism of unsaturated fatty acids, odd-chain-length fatty acids, and medium-chain-length fatty acids requires variations of this basic pattern. The acetyl CoA produced from fatty acid oxidation is principally oxidized in the TCA cycle or converted to ketone bodies in the liver. 

Not established. A possible reason is that isoniazid induces the cytochrome P450 isoenzyme CYP2E1 by stabilisation. This means that while the isoniazid is still present, the metabolism of substrates such as paracetamol is inhibited. However, when isoniazid levels drop sufficiently (as may be the case late in the dosing interval in fast acetylators), metabolism may be induced resulting in a greater proportion of the paracetamol being converted into toxic metabolites than would normally occur. ... 

In 21 healthy subjects, allopurinol 300 mg daily for 8 days altered the levels of urinary caffeine metabolites of a single 200-mg dose of caffeine. In particular, the metabolic ratio used to determine whether people are fast or slow acetylators was substantially changed. Thus, allopurinol may invalidate the results of phenotyping with the urinary caffeine test. In addition, the caffeine metabolite ratio used to express the activity of the cytochrome P450 isoenzyme CYP1A2 was not stable when allopurinol was used. This interaction is of relevance to research rather than clinical practice. 

Isoniazid appears to cause a dual interaction. During administration, it inhibits the activity of cytochrome P450 isoenzyme CYP2E1, the enzyme involved in the metabolism of chlorzoxazone. Shortly after stopping isoniazid, the metabolism of chlorzoxazone is increased, possibly because of induction of CYP2E1, although this effect was only evident in the slow acetylators. ... 

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