Hydrolase reactions

The probable metabohc defect in type I tyrosine-mia (tyrosinosis) is at himarylacetoacetate hydrolase (reaction 4, Figure 30-12). Therapy employs a diet low in tyrosine and phenylalanine. Untreated acute and chronic tyrosinosis leads to death from liver failure. Alternate metabolites of tyrosine are also excreted in type II tyrosinemia (Richner-Hanhart syndrome), a defect in tyrosine aminotransferase (reaction 1, Figure 30-12), and in neonatal tyrosinemia, due to lowered y>-hydroxyphenylpyruvate hydroxylase activity (reaction 2, Figure 30-12). Therapy employs a diet low in protein. 

Scheme 6. Stereochemical features of the epoxide hydrolase reaction.

Fig. 10.27. Mechanistic and stereochemical aspects of the hydration of trans-(R,K)-anethole epoxide in the absence (Reactions a and b) and presence of epoxide hydrolase (Reaction c) [178][179]. The ratio of Reaction a to bis ca. 4 1 in acid- and base-catalyzed hydration to yield the threo- and erythro-diols, respectively. The enzymatic Reaction c also yields preferentially the erythro-diol.

Faber, K., Ottolina, G. andRiva, S. (1993) Selectivity-Enhancement of Hydrolase Reactions. Biocatalysis, 8, 91-132. 

Alloxan has been reported to increase VmflI values of the hydrolase reaction as well as to increase Km for glucose-6-P (140). 

Row reduction of the conservation matrix A for this reaction based on element balances for C, O, and P indicates that there is a single reaction. However, this is a misleading result because a column for h2o is not included in A, and this excludes the possible hydrolase reactions ... 

Note that there is an error in reference 6 in that the h2o is missing.) Ligase reactions necessarily involve coupling because they are defined (7) as "joining together of two molecules coupled with the hydrolysis of a pyrophosphate bond in atp of a similar triphosphate." This enzyme couples three hydrolase reactions ... 

To show the tremendous range of values of apparent equilibrium constants for hydrolase reactions at 298.15 K, pH 7, and 0.25 M ionic strength, a table is prepared in order of increasing values. 

The effects of temperature on thermodynamic properties of hydrolase reactions have been calculated for six phosphate hydrolysis reactions and three other hydrolase reactions in Chapter 4. The effects of temperature for 20 hydrolase reactions are discussed in Chapter 13. 

Hydrolase reactions do not involve coupling, but they do involve a problem with the treatment of water in biochemical thermodynamics. Therefore, it is of interest to consider their representation by matrices. As a prototypical hydrolase reaction, consider the hydrolysis of glucose 5-phosphate. 

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