Uridylyltransferase

A rare hereditary condition known as galactosemia involves defects in galac-tose-l-P uridylyltransferase that render the enzyme inactive. Toxic levels of... 

FIGURE 19.34 The galactose-l-phosphate uridylyltransferase reaction involves a ping-pong kinetic mechanism. 

This enzyme [EC 2.7.7.10], also known as UTP hexose-1-phosphate uridylyltransferase, catalyzes the reaction of UTP with a-D-galactose 1-phosphate to produce UDP-galactose and pyrophosphate (or, diphosphate), a-o-Glucose 1-phosphate can also function as a substrate, albeit not as effectively. 

T14. Severity of Clinical Symptoms Due to Enzyme Deficiency The clinical symptoms of two forms of galactosemia—deficiency of galactokinase or of UDP-glucose galactose 1-phosphate uridylyltransferase— show radically different severity. Although both types produce gastric discomfort after milk ingestion, deficiency of the transferase also leads to liver, kidney, spleen, and brain dysfunction and eventual death. What products accumulate in the blood and tissues with each type of enzyme deficiency Estimate the relative toxicities of these products from the above information. 

M FIGURE 22-7 Second level of regulation of glutamine synthetase covalent modifications, (a) An adenylylated Tyr residue, (b) Cascade leading to adenylylation (inactivation) of glutamine synthetase. AT represents adenylyltransferase UT, uridylyltransferase. Details of this cascade are discussed in the text. 

Under conditions of nitrogen limitation, the first regulatory enzyme in the cascade is converted into a uridylyltransferase. This enzyme uridylates the PII protein. The PII 3 UMP protein and adenylyltransferase deadenyly-lates the glutamine synthase, 12 AMP. 

Answer In galactokinase deficiency, galactose accumulates in UDP-glucose galactose 1-phosphate uridylyltransferase deficiency, galactose 1-phosphate accumulates (see Fig. 14-12). The latter metabolite is clearly more toxic. 

Case B (c) Galactose 1-phosphate uridylyltransferase is an enzyme involved in conversion of galactose to glucose, which then can enter glycolysis. Absence of this enzyme leads to accumulation of galactose in the blood and excretion in the urine. A patient with this deficiency should be on a low-lactose diet (treatment 3). 

An analogous approach was used to show that galactose-1-P uridylyltransferase catalyzes the interconversion of UDP-glucose and galactose- -P with UDP-galactose and glucose-1-P with retention of configuration at PQ [21]. The stereochemical transformations used in the analysis are shown in Equation 14. 

Two pairs of chemically matched reactions exemplify the importance of shared binding sites in the evolution of double-displacement pathways. They are the reactions catalyzed by UDP-glucose pyrophosphorylase (inversion) [74] and galactose- -P uridylyltransferase (retention) [21], which catalyze Reactions 21 and 22,... 

UDP-Glc is the principal sugar nucleotide and UTP Glc 1-P uridylyltransferase is the major sugar nucleotide transferase in plant tissues (Feingold, 1982). Apart from its role in the SNOP, the transferase functions as glycosyl donor to sucrose, starch, callose, and cellulose (Hopper and Dickinson, 1972 Schlupmann et al., 1994 Tenhaken and Thulke, 1996). UDP-Glc inhibits this... 

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