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Biomedical subjects

H N Kirkman

Publications and source records attributed to H N Kirkman.

At least 37 records · Page 2Linked to original sources
PubMed1984

Catalase: a tetrameric enzyme with four tightly bound molecules of NADPH.

Catalases (H2O2:H2O2 oxidoreductase, EC 1.11.1.6) from many species are known to be tetramers of 60,000-dalton subunits, with four heme groups per tetramer. Previous authors have determined the amino acid sequence and three-dimensional structure of bovine liver catalase. Studies of the regulation of the pentose phosphate pathway led the present authors to a search for proteins that bind NADP+ and NADPH in human erythrocytes. An unexpected result of that search was the finding that a major reservoir of bound NADPH in human erythrocytes is catalase. Each tetrameric molecule of human or bovine catalase contains four molecules of tightly bound NADPH. The binding sites have the relative affinities NADPH greater than NADH greater than NADP+ greater than NAD+. NADPH does not seem to be essential for the enzymic conversion of H2O2 to O2 and water but does provide protection of catalase against inactivation by H2O2.

Animals↗
PubMed1983

Intracellular glucose-6-phosphate dehydrogenase does not monomerize in human erythrocytes.

Glucose-6-phosphate dehydrogenase functions within human erythrocytes at a rate far less than expected from kinetic properties of the purified enzyme and from estimated concentrations of enzyme, substrates, and products. Several investigators have proposed that activity of glucose-6-phosphate dehydrogenase is less than maximal because the enzyme is regulated by equilibration between an active dimeric form of the enzyme and an inactive monomer. The phenomenon of Lyonization provided an opportunity for this proposal to be tested. Erythrocytes of a glucose-6-phosphate dehydrogenase A/B heterozygous woman were gently lysed and resealed so that each erythrocyte contained the two homodimers AA and BB. Subsequent lysis and electrophoresis revealed no heterodimer. This finding indicates that intracellular factors other than reversible dissociation account for the restraint of human glucose-6-phosphate dehydrogenase.

Electrophoresis, Cellulose Acetate↗
PubMed1982

Projections of a rebound in frequency of mental retardation from phenylketonuria.

The present decade marks the end of a unique generation--when the public benefited from the prevention of mental retardation phenylketonuria (PKU) without having to deal fully with the problems which can be anticipated from the reproduction of successfully treated, phenylketonuric individuals. The dysgenic effect (increase in prevalence of the PKU gene) from this reproduction will have negligible influence on the frequency of mental retardation from PKU over the next few centuries. In contrast, a dysgenic effect from maternal PKU will cause a rebound in frequency of mental retardation within this decade. Failure of the PKU programs as a result of maternal PKU, could affect the public attitude toward programs for the study and prevention of mental retardation and genetic diseases. Minimizing and explaining the rebound in frequency of mental retardation will be a difficult but necessary task for workers in the field of mental retardation.

Adolescent↗
PubMed1982

Fifteen-year experience with screening for phenylketonuria with an automated fluorometric method.

An automated fluorometric method, rather than the Guthrie test, has been used in North Carolina for neonatal screening for phenylketonuria (PKU). Although there is no testing law, 97% of newborn infants are screened. Twelve children with PkU, not referred for dietary management, were born before the screening program was established, were born elsewhere, or were successfully identified at birth but not referred for treatment. None was missed because of laboratory error or because of the lack of a testing law. Positive skewing was noted among initial blood phenylalanine levels of 49 infants with PKU and severe hyperphenylalaninemia. Log transformations caused the values to be normally distributed and permitted the calculation of tolerance and confidence limits. These provided estimates of the percentage of phenylketonuric infants whose initial blood levels might fall below any given cutoff value.

Age Factors↗
PubMed1981

Genetic screening of donors for artificial insemination.

A routine has been established for genetic screening of donors in an artificial insemination and frozen sperm bank program. This report is a summary and analysis of the information obtained on the first 168 donor applicants and 89 recipients who were genetically screened. The specific forms for screening, family information obtained, characteristics of the donor and recipient groups, and guidelines for acceptance or rejection of donors are discussed. The donor and recipient often failed to perceive that the disorders in the family were genetic. The simple question of whether or not there were genetic or hereditary problems in the family was ineffective, even when the donor or recipient had formal medical training.

Age Factors↗
PubMed1980

Regulation of glucose-6-phosphate dehydrogenase. I. Intact red cells.

The intracellular levels of substates and products of G6PD were measured in normal human red cells that were incubated in a Krebs-Ringer buffer without methylene blue and with increasing amounts of methylene blue. The use of [1-14C]glucose and [2-14C]glucose allowed estimates of the rate at which the G6PD was functioning within the cell. Kinetic characteristics of the purified enzyme were determined in the same Krebs-Ringer buffer. G6PD of normal red cells exhibits two unusual properties. (1) The intracellular enzyme is under unexplained intracellular restraint that ranges from 200-fold (if most of the NADP is in the reduced form) to five-fold (if most of the NADP is in the oxidized form). When coupled with earlier reports, these findings suggest that unexplained intracellular restraint is common to both G6PD-normal and G6PD-deficient (A-) red cells, (2) A highly sigmoid curve is obtained when the rate of the intracellular enzyme is plotted against the ratio of oxidized NADP to total NADP. In contrast, a nearly straight line is obtained with the corresponding plot of the pure enzyme under similar conditions of buffer and substrate concentration.

Erythrocytes↗
PubMed1980

Regulation of glucose-6-phosphate dehydrogenase. II. Resealed red cell ghosts.

Resealed red cell ghosts were prepared at a final dilution of 1:325 from normal and G6PD-deficient cells. The activity of the HMS and concentrations of G6P, ATP, and total and reduced nictinamide adenine dinucleotide phosphate were determined after incubation in the presence of 0 and 100 micrometer methylene blue. The results indicate that the HMS is still under ununexplained restraint in the resealed cells but that the restraint has been reduced between twofold and fourfold from that observed in the intact normal red cells. The addition of various combinations of ATP, hexokinase, and methylene blue led to the demonstration that the unexplained restraint is not significantly correlated with levels of ATP or G6P. As with intact red cells, however, the explained restraint is greatest under conditions that cause the level of NADP+ to be low and that of NADPH to be high.

Erythrocyte Membrane↗
PubMed1978

Prenatal diagnosis by linkage: hemophilia A and polymorphic glucose-6-phosphate deydrogenase.

Close linkage between the loci for G6PD and hemophilia A allows prenatal diagnosis of hemophilia in the fetuses of certain women who are heterozygous for two electrophoretic types of G6PD. A pregnant woman, whose mother was an obligate heterozygote for hemophilia, had factor VIII levels and a G6PD phenotype that failed to indicate clearly whether or not she was heterozygous for hemophilia. The G6PD phenotype of her male fetus revealed that the fetus was unlikely to have hemophilia.

Female↗