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Title: Genetic control of glycolysis in human erythrocytes

We have studied heritability of the concentration of each glycolytic intermediate and adenine nucleotide in the cytosol of human erythrocytes obtained from a random sample of apparently healthy young individuals. Preliminary to analysis of heritability, each trait was statistically described and the effects attributable to variation in measured concomitants were removed by regression. Heritability was estimated using the family-set method. This method removes covariances between the index case, sibling and first cousin, due to those environmental determinants of the phenotypic values that are shared with a matched, unrelated control member of the family set. It also removes covariances due to environments that are shared by siblings and first cousins. Heritability was estimated by employing the fact that the variance of differences between first cousins minus the variance of differences between full siblings estimates three-fourths of the additive genetic variance. The heritability estimates for G6P, F6P, ATP and some other metabolite concentrations are high and significantly greater than zero. The heritabilities of G6P and F6P are likely attributable to genetic variation in the in vivo activity of HK and/or PFK, because the concentrations of these metabolites are tightly controlled by the two regulatory enzymes. Statistically significant heritability estimates for HK andmore » PFK mass action ratios stronglysuggest genes are responsible for a portion of the quantitative variation in these enzyme activities. Since HK and PFK regulate glycolysis and the production of ATP, genetic variation in their activities might be causally related to the heritability of ATP concentration.« less
Authors:
; ;
Publication Date:
OSTI Identifier:
5059927
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genetics; (United States); Journal Volume: 94:3
Research Org:
Univ. of Michigan Medical School, Ann Arbor
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ERYTHROCYTES; GENETICS; GLYCOLYSIS; GENETIC VARIABILITY; ADENINES; ATP; ENZYMES; GENES; METABOLISM; METABOLITES; QUANTITY RATIO; AMINES; BIOLOGICAL MATERIALS; BIOLOGICAL VARIABILITY; BIOLOGY; BLOOD; BLOOD CELLS; BODY FLUIDS; CHEMICAL REACTIONS; DECOMPOSITION; HETEROCYCLIC COMPOUNDS; MATERIALS; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PURINES 550400* -- Genetics; 550500 -- Metabolism