Glutamyl

The 7 glutamyl phosphate formed m this step is a mixed anhydride of glutamic acid and phosphoric acid It is activated toward nucleophilic acyl substitution and gives glutamine when attacked by ammonia... 

Enzymes, measured in clinical laboratories, for which kits are available include y-glutamyl transferase (GGT), alanine transferase [9000-86-6] (ALT), aldolase, a-amylase [9000-90-2] aspartate aminotransferase [9000-97-9], creatine kinase and its isoenzymes, galactose-l-phosphate uridyl transferase, Hpase, malate dehydrogenase [9001 -64-3], 5 -nucleotidase, phosphohexose isomerase, and pymvate kinase [9001-59-6]. One example is the measurement of aspartate aminotransferase, where the reaction is followed by monitoring the loss of NADH ... 

Work in the mid-1970s demonstrated that the vitamin K-dependent step in prothrombin synthesis was the conversion of glutamyl residues to y-carboxyglutamyl residues. Subsequent studies more cleady defined the role of vitamin K in this conversion and have led to the current theory that the vitamin K-dependent carboxylation reaction is essentially a two-step process which first involves generation of a carbanion at the y-position of the glutamyl (Gla) residue. This event is coupled with the epoxidation of the reduced form of vitamin K and in a subsequent step, the carbanion is carboxylated (77—80). Studies have provided thermochemical confirmation for the mechanism of vitamin K and have shown the oxidation of vitamin KH2 (15) can produce a base of sufficient strength to deprotonate the y-position of the glutamate (81—83). 

L-jS-Pyrazolylalanine (755) and y-L-glutamyl-/8-pyrazol-L-alanine are found in the seeds of many speeies of Cucurbitaceae (65P933). It was subsequently demonstrated that free pyrazole oeeurs in watermelon seeds in eoneentrations of 280 to 410 jLg g depending on the variety (75P2512). Biosynthetic studies implieate 1,3-diaminopropane as a precursor of the pyrazole moiety of (755) (82P863). 

Alanine, ( )- -(2-amino-1,3-selenazol-4-yl)-synthesis, 6, 343 Alanine, phenyl-p-hydroxylation, 7, 565 Alanine, selenienyl-synthesis, 4, 964 Alanine, y3-2-selenienyl-applications, 4, 970 Alanine, y3-3-selenienyl-applications, 4, 970 Alanine, y3-2-thienyl-biological activity, 4, 911 Alanine, -3-thienyl-biological activity, 4, 912 L-Alanine, y-L-glutamyl-y3-pyrazolyl-occurrence, 5, 303 L-Alanine, -pyrazolyl-occurrence, 5, 303 Alanine raeemase inhibition, 1, 266 Albendazole... 

FIGURE 18.40 The glutamyl carboxylase reaction is vitamin K-dependent. This enzyme activity is essential for the formation of 7-car-boxyglutamyl residues in several proteins of the blood-clotting cascade (Figure 15.5), accounting for the vitamin K dependence of coagulation. 

The cyclic sulfoximine 93a,b, a key intermediate in the synthesis of sulfoximine 94 designed as inhibitors of Escherichia Coli y-glutamyl synthetase, was synthesized stereoselectively (96BMC(6)1437, 98BMC(6)1935). X-ray analysis (99AX(C55)1598) of 93b was performed, elucidating the configuration. 

Antithyroid drags have several side effects. The most frequent side effects are maculopapular rashes, pruritus, urticaria, fever, arthralgia and swelling of the joints. They occur in 1-5% of patients [1, 2]. Loss of scalp hair, gastrointestinal problems, elevations of bone isoenzyme of alkaline phosphatase and abnormalities of taste and smell are less common. The incidence of all these untoward reactions is similar with MMI and PTU. Side effects of MMI are dose-related, whereas those of PTU are less clearly related to dose [1]. PTU may cause slight transient increases of serum aminotransferase and y-glutamyl transpeptidase concentrations but also severe hq atotoxicity whereas methimazole or carbimazole can be associated with cholestasis. The side... 

Folic acid or folate (Fig. 1) is the collective name for more than 100 derivatives of pteroyl-mono-L-gluta-mate. In plant and animal tissues, folic acid mostly occurs as pteroyloligo-L-glutamate (PteGluJ, with up to eight glutamyl residues. 

Activities of glutamate-pyruvate transaminase (SGPT, GPT) (EC 2.6.1.2), L-y -glutamyl-transferase (y-GT) (EC 2.3.2.2) and level of triglycerides (TG) in serum, as well as levels of glutathione (GSH) and malondialdehyde (MDA) in the liver were determined. 

Gamma-glutamyl-transferase activity was determined according to "Monotest 10 y-GT neu" from Boehringer-Mannheim. 

In subsequent experiments (66), this locked substrate was used to obtain evidence for the hypothesis (67) that enzyme-bound y-glutamyl phosphate 14 is an intermediate in the enzyme-catalyzed reaction. All attempts to isolate this acyl phosphate 14 have failed (66), presumably because of the marked tendency of this intermediate to cyclize to pyrrolidonecarboxyUc acid, 15, and to hydrolyze to glutamic acid. 

Panetta JC, Wall A, Pui CH, Rolling MV, Evans WE. Methotrexate intracellular disposition in acute lymphoblastic leukemia a mathematical model of gamma-glutamyl hydrolase activity. Clin Cancer Res 2002 8 2423-9. 

Figure 3-3. Glutathione (y-glutamyl-cysteinyl-glycine). Note the non-a peptide bond that links Glu to Cys.

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