Scientists in the fields of nutrition and other biological sciences often design factorial studies to test the hypotheses of interest and importance. In the case of two-factorial studies, it is widely recognized that the analysis of factor effects is generally based on treatment means when the interaction of the factors is statistically significant, and involves multiple comparisons of treatment means. However, when the two factors do not interact, a common understanding among biologists is that comparisons among treatment means cannot or should not be made. Here, we bring this misconception into the attention of researchers. Additionally, we indicate what kind of comparisons among the treatment means can be performed when there is a nonsignificant interaction among two factors. Such information should be useful in analyzing the experimental data and drawing meaningful conclusions.
Deficiency of uridine-5'-monophosphate (UMP) synthase in dairy cattle, a condition analogous to human hereditary orotic aciduria, is reviewed with consideration of similarities and differences between the enzyme deficiency in humans and cattle. New findings regarding the bovine condition are reported including presence of the enzyme deficiency in numerous tissues and absence of substantial effects on other aspects of nucleotide metabolism. Specifically, erythrocyte concentration of phosphoribosylpyrophosphate (PRPP) and activities of PRPP synthetase, adenine phosphoribosyltransferase, and hypoxanthine-guanine phosphoribosyltransferase appear to be normal in cattle heterozygous for UMP synthase deficiency.
UMP synthase was characterized biochemically in dairy cattle heterozygous for a deficiency of this enzyme. Both activities comprising this bifunctional enzyme are decreased, with OMP decarboxylase more affected than orotate phosphoribosyltransferase. Immunotitration of UMP synthase activity revealed the presence of the protein product of the mutant allele in the heterozygous animals. UMP synthases from normal and deficient cattle were not distinguished from one another by kinetic constants, responses to inhibitors, pH profiles, or thermal lability. It was concluded that the 50% reduction in enzyme activity in heterozygous cattle is the result of the presence of only half the normal level of catalytically active UMP synthase.
Effects of 1% dietary orotic acid on lipid metabolism were examined in rats, mice, hamsters and guinea pigs. The influences of diet composition, age and sex on alterations induced by orotic acid were also studied. Hypocholesteremia and hepatic steatosis developed in rats fed orotic acid. These responses were little affected by dietary changes in lipid (0, 2 or 5% corn oil) or carbohydrate (high sucrose, high starch or high fiber). When included in diets containing cholesterol and cholic acid, orotic acid prevented a rise in serum cholesterol but did not maintain a normal ratio of HDL to total cholesterol. The responses of mice to orotic acid were opposite to those of rats; liver lipid was decreased, and serum cholesterol was increased. Hamsters and guinea pigs were unaffected by the compound. Thus, orotic acid is hypocholesteremic in rats, hypercholesteremic in mice and normocholesteremic in hamsters and guinea pigs. Age did not alter responses of rats to 1% dietary orotic acid. In rats and mice, sex influenced changes in hepatic lipid, with females more responsive than males.
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