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G Bulfield

Publications and source records attributed to G Bulfield.

At least 55 records · Page 3Linked to original sources
PubMed1981

Polymorphism of kidney pyruvate kinase in the mouse is determined by a gene, Pk-3, on chromosome 9.

An electrophoretically detectable variant of pyruvate kinase (EC 2.7.1.40) has been found in the house mouse Mus musculus. The variant was seen in all tissues examined except liver and red cells. The gene (Pk-3) determining this electrophoretic variation is inherited as an autosomal codominant located on chromosome 9. Our data confirm that the genetic determination of pyruvate kinase in liver and red cells is separate from that in other tissues. In addition, our results indicate that the muscle (M1) and kidney (M2) pyruvate kinase isozymes share at least one genetic determinant and may in fact be determined by the same structural gene.

Animals↗
PubMed1981

An allele (Pk-1b) from wild-caught mice that affects the activity and kinetics of erythrocyte and liver pyruvate kinase.

A true breeding strain was made from a wild-caught mouse with low erythrocyte pyruvate kinase (E.C. 2.7.1.40) activity. This variation showed additive inheritance and segregated as an allele at a single locus (Pk-1b). Mice homozygous for the reduced blood pyruvate kinase activity cosegregated for reduced liver activity. In both these tissues the variant enzyme had a lowered heat stability and reduced Km values for ADP. An increased stimulation by FDP was also detected in the liver pyruvate kinase. No difference in the isoelectric point of the variant enzyme in either erythrocyte or liver was observed when compared with the enzyme from C57BL mice (Pk-1a/Pk-1a). It is concluded that Pk-1 is the structural gene for the erythrocyte and the major liver pyruvate kinase. No other tissue pyruvate kinase showed altered characteristics.

Alleles↗
PubMed1981

Genetic variation in erythrocyte NAD levels in the mouse and its effect on glyceraldehyde phosphate dehydrogenase activity and stability.

During a screening of inbred strains for enzyme variation in glycolysis, differences were found in glyceraldehyde phosphate dehydrogenase (GAPDH) activity between C57BL/6J and SM/J mice. Segregation analysis did not reveal unequivocal monogenic inheritance. Dialysis of hemolysates caused decay of enzyme activity, especially in C57BL animals, which could be prevented by the presence of NAD. This led to the finding that erythrocyte NAD levels were threefold higher in SM than C57BL animals and, although additively inherited, did not appear to be monogenic. This is comparable with but independent of the differences and effect of erythrocyte NADP levels on glucose-6 phosphate dehydrogenase activity reported by R. P. Erickson (1974) Biochem. Genet. 11:33] and emphasizes the range of mechanisms that can be involved in the genetic control of enzyme activity in mammalian systems.

Animals↗
PubMed1980

Inherited metabolic disease in laboratory animals: a review.

Research on the screening for and study of animal models of inherited metabolic disease is reviewed. It is emphasized that an animal model, to be of value, must be an inherited deficiency of the same enzyme as the one deficient in the human syndrome. If this criterion is adhered to there is a remarkable identity in aetiology between animal and man. Specific examples of inherited metabolic disease in laboratory animals are described for: amino acid metabolism; lysosomal storage diseases, carbohydrate metabolism, transport disorders and trace element metabolism; the mutants found in mice being the easiest to manipulate biochemically and genetically. There is still a lack of adequate screening programmes for animal homologues of the more serious human inborn errors (such as lysosomal storage diseases) where laboratory studies could provide significant advances in therapy.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice.

We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported.

Alleles↗
PubMed1978

Genetic variation in the activity of the histidine catabolic enzymes between inbred strains of mice: a structural locus for a cytosol histidine aminotransferase isozyme (Hat-1).

Variation in activity of the main histidine catabolic enzymes (histidase, urocanase, and aminotransferase) has been surveyed using inbred strains of mice (C57BL, DBA, Peru, SM, and SWR). Some variation was found in the activity of all enzymes, but only in the case of cytosolic histidine aminotransferase was it greater than twofold (SM 3.3-fold greater than C57BL). The divergent strains for the activity of this enzyme were crossed and the F1's were backcrossed; the segregation analysis indicated a single locus with additively acting alleles (designated Hat-1: a allele SM, b allele C57BL). Cytosolic histidine aminotransferase differed in heat stability between SM and C57BL, indicating that Hat-1 is a structural locus. The conflict in the biochemical literature (Morris et al., 1973; Noguchi et al., 1976a,b) over the number and subcellular distribution of the histidine aminotransferase isozymes is partly resolved by the acquisition of a variant at the Hat-1 locus. Hat-1 affects the cytosolic form but not the mitochondrial form of the enzyme. Purification and analysis of the isozymes of histidine aminotransferase from livers of C57BL and SM mice will further clarify the situation.

Animals↗
PubMed1978

Effect of the mouse mutants testicular feminization and sex reversal on hormone-mediated induction and repression of enzymes.

The mouse mutants testicular feminization and sex reversal have been used to investigate hormone-mediated induction and repression of enzymes. Tfm/Y animals were already known to be androgen insensitive, rendering the androgen-inducible enzymes ADH and beta-glucuronidase noninducible because of an inherited deficiency of a cytosol androgen-receptor complex. The animals display female secondary sexual characteristics. Sxr/+,XX animals display male primary and secondary sexual characteristics with small testes. We demonstrate (1) that the Tfm mutation is pleiotropic, preventing repression of an androgen-repressible enzyme (ornithine aminotransferase) as well as induction of androgen-inducible enzymes, (2) that an estrogen-inducible enzyme (histidine decarboxylase) is not affected by the Tfm mutation, and (3) that Sxr/+,XX animals produce enough androgen for malelike activities of androgen-sensitive enzymes. It was also discovered that histidine decarboxylase repressed by androgen in normal animals, rather than being unaffected by it in Tfm/Y animals, is in fact induced. This unexpected phenomenon is discussed and an explanation is suggested for it.

Alcohol Oxidoreductases↗
PubMed1978

Genetic variation in activity of the enzymes of glycolysis and gluconeogenesis between inbred strains of mice.

Variation in the activity of 21 liver and 15 erythrocyte enzymes between seven inbred strains of mice has been studied in a single area of metabolism, glycolysis and gluconeogenesis. Most of the variation between the strains is genetic. From the variation within and between inbred strains heritabilities (H2) were determined. Out of 35, 26 showed significant values above 0.4. A comparison with previously published work suggests that enzyme activities have mainly dominance and interaction components of variance, and this is discussed in relation to the variation in quantitative characters such as growth. In nine of the pairwise comparisons of the strains, the activity of the enzyme varied more than two-fold. In these cases the genetics and biochemistry of the enzyme was studied; F2 progeny were produced and assessed for segregation, and the heat stability of the enzyme was determined. No unequivocal segregation was observed, although in one case we found a considerable difference in heat stability. The variations found were not considered to be great enough to be useful as models of human inborn errors of metabolism or to study metabolic control. If such variants are to be found, sources of variation other than inbred strains must be used.

Animals↗