Uracil phosphoribosyltransferase specificity

A pyrimidine phosphoribosyltransferase activity with a broader specificity than the yeast enzyme has been demonstrated in animal tissues. Highly purified preparations from calf thymus (15) and beef erythrocytes (16) accepted orotate and 5-fluorouracil as substrates. Uracil phosphoribosyltransferase activity has also been demonstrated in extracts from mouse leukemia cells. Fluorouracil is a better substrate for this enzyme than uracil at pH 7.5, possibly because the acid dissociation constant for the analogue (pif 8.15) is higher than that of uracil (pK, 9.45) (17). This reasoning would suggest that the anionic form of the substrate might be the species required by the enzyme. This enzyme has been implicated in the... 

Uracil phosphoribosyltransferase has been demonstrated in the uracil-requiring protozoan, Teirahymena pyriformis, and has been partly purified, but the substrate specificity of the preparation was not investigated 17). 

The first reaction is catalysed by orotate phosphoribosyltransferase (orotidine 5 -phosphate pyrophosphate phosphoribosyltransferase, EC 2.4.2.10) which is readily reversible. The equilibrium constant for the forward reaction [109] is about 0.1. The reaction is specific for orotate (the enzyme usually does not accept uracil) and some synthetic analogues of orotic acid (Chapter 6). Orotate phosphoribosyltransferase activity was found in many animal tissues [110] and there are several phosphoribosyl-transferases of broad specifity which are distinct from the enzyme involved in the orotate pathway [111-113]. 

Two routes are known by which the free base, uracU, can enter the ribonucleotide pool. One proceeds by the sequential actions of uridine phosphorylase and uridine-cytidine kinase (reactions 5 and 6, Fig. 12-1) this route is discussed below. The other route is by way of a single-step phosphoribosyltransferase reaction specific for uracil (reaction 4, Fig. 12-1) ... 

The orotate phosphoribosyltransferase of yeast is specific for orotate and will not accept uracil as a substrate. This enzyme occurs in most animal cells as part of the de novo pathway of pyrimidine biosynthesis, but the specificity of the animal enzyme is unknown. Animal cells have a phosphoribosyltransferase activity capable of accepting pyrimidine substrates other than orotate, but it is not clear whether this is due to a phosphoribosyltransferase distinct from that of the orotate pathway (see Chapter 11). 

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