Alanine transpeptidase

Penicillin inhibits a D-alanyl-D-alanine transpeptidase that catalyzes the reaction... 

The /3-lactam bond is broken (instead of the equivalent peptide bond joining the alanine residues) but the remaining ring system in the /3-lactam (a thiazolidine in penicillins) is not released (Fig. 8.3). Instead, the transpeptidase remains linked to the hydrolysed antibiotic with a half hfe of 10-15 minutes. Whilst bound to the / -lactam, the transpeptidase cannot participate in further rounds of peptidoglycan... 

Fig. 8.2 Interaction of transpeptidase (Enz) with its natural substrate, acyl-D-alanyl-D-alanine in the first stage of the transpeptidation reaction to form an acyl-enzyme intermediate. A similar reaction with a penicillin results in the formation of an inactive penicilloyl-enyme complex.

Elevated aspartate transaminase (AST), alanine transaminase (ALT), and /glutamyl transpeptidase (GGT)... 

Routine liver assessment tests include alkaline phosphatase, bilirubin, aspartate transaminase, alanine transaminase, and y-glutamyl transpeptidase (GGT). Additional markers of hepatic synthetic activity include albumin and prothrombin time. The substances are typically elevated in chronic inflammatory liver diseases such as hepatitis C, but may be normal in others with resolved infectious processes. 

FIGURE 21-1. Interpretation of liver function tests. (ALT, alanine transaminase AST, aspartate transaminase CT, computed tomography DDX, differential diagnosis GGT, y-glutamyl transpeptidase.)... 

ALANINE AMINOTRANSFERASE y-GLUTAMYL TRANSPEPTIDASE l-SELENOCYSTEINE 13-LYASE d-ALANINE-d-ALANINE LIGASE ALANINE AMINOTRANSFERASE... 

The third and final stage of synthesis of cell walls occurs outside the cytoplasmic membrane. Thus, the transpepfidation reaction results in transformation of the linear glycopeptide polymer into the CTOss-Unked form. The enzyme transpeptidase, a membrane-bound enzyme, binds pentapepfide side chains by replacing terminal o-alanines. 

The (3-lactam antibiotics structurally resemble the terminal D-alanyl-D-alanine (o-Ala-o-Ala) in the pen-tapeptides on peptidoglycan (murein) (Fig. 45.1). Bacterial transpeptidases covalently bind the (3-lactam antibiotics at the enzyme active site, and the resultant acyl enzyme molecule is stable and inactive. The intact (3-lactam ring is required for antibiotic action. The (3-lactam ring modifies the active serine site on transpeptidases and blocks further enzyme function. 

During the biosynthesis of the cell wall, the muropeptide is formed from acetylmuramyl-pentapeptide, which terminates in a D-alanyl-D-alanine. The synthesis of this precursor is inhibited by the antibiotic cycloserine (9.36), a compound produced by many Streptomyces fungi but which is not used clinically. During the crosslinking of the pen-tapeptide precursor, the terminal fifth alanine must be split off by a transpeptidase enzyme. This last reaction in cell wall synthesis is inhibited by the p-lactam antibiotics. 

The inhibitory mechanism is shown in figure 16.20. First the transpeptidase (TPase) reacts with one strand of the substrate to form an acyl enzyme intermediate, thus eliminating D-alanine. This intermediate then reacts with another strand to form the cross-link and regenerate the enzyme. Because penicillin is an analog of alanylalanine, it fits... 

A 54-year-old woman had fatigue and dark urine after taking acarbose 50 mg tds for 5 months (57). Her aspartate transaminase was 2436 U/l, alanine transaminase 2556 U/l, y-glutamyl transpeptidase 601 U/l, and alkaline phosphatase 174 U/l serology was negative and she had a normal liver and gall bladder on ultrasound. Her liver enzymes normalized 5 months after withdrawal. 

Occupational exposure to chromium(III) or chromium(O) does not appear to be associated with renal effects. No renal impairment based on urinary albumin, retinol binding protein, and renal tubular antigens was found in 236 workers employed in the ferrochromium production industry where ferrochromite is reduced with coke, bauxite, and quartzite. The mean airborne concentration of chromium in various sample locations was 0.075 mg chromium(III)/m3 chromium(VI) was below the detection limit of 0.001 mg chromium(VI)/m3 at all locations (Foa et al. 1988). Workers employed in an alloy steel plant with a mean exposure of 7 years to metallic chromium at 0.61 mg chromium(0)/m3 and to other metals had normal urinary levels of total protein and p2-microglobulin, enzyme activities of alanine-aminopeptidase, N-acetyl-P-D-glucosaminidase, gammaglutamyl-transpeptidase, and P-galactosi-dase (Triebig et al. 1987). In boilermakers exposed to chromium(O), no increase in urinary levels of... 

The cross-linking (transpeptidation) of the peptidoglycan chains is facilitated by transpeptidases known as penicillin-binding proteins. 3-lactam antibiotics are analognes of D-alanyl-D-alanine, the terminal amino acid residnes on the precursor N-acetyhnuramic/N-acetylglucosamine (NAM/NAG)-peptide subunits of the nascent peptidoglycan layer. The structural similarity between /3-lactam antibiotics and D-alanyl-D-alanine facilitates their... 

Penicillin inhibits the cross-linking transpeptidase by the Trojan horse stratagem. The transpeptidase normally forms an acyl intermediate with the penultimate d-alanine residue of the d-Ala-d-Ala peptide (Figure 8.29). This covalent acyl-enzyme intermediate then reacts with the amino group of the terminal glycine in another peptide to form the cross-link. Penicillin is welcomed into the active site of the transpeptidase because it mimics the d-Ala-d-Ala moiety of the normal substrate (Figure 8.30). Bound penicillin then forms a covalent bond with a serine residue at the active site of the enzyme. This penicilloyl-enzyme does not react further. Hence, the transpeptidase is irreversibly inhibited and cell-wall synthesis cannot take place. 

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