Phosphohexokinase Activity of Erythrocytes in Mongolism Another Possible Marker for Chromosome 21

Baikie, A.G.; Loder, P. Bronwen; Gruchy, G. C. de; Pitt, David

doi:10.1016/s0140-6736(65)90007-3

Cited by 69 publications

(15 citation statements)

References 16 publications

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“…In contrast, increased PFK activity has been found in individuals with trisomy 21 (Down syndrome). In these individuals, the =50% increase in RBC PFK has led to the hypothesis that this might be a gene-dosage effect resulting from the presence of a gene for PFK on chromosome 21 (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody.

Vora¹,

Francke²

1981

Proc. Natl. Acad. Sci. U.S.A.

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Human 6-phosphofructokinase (PFK; ATP:Dfructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) is under the control of structural loci that code for muscle (M), liver (L), and platelet (P) subunits, which are variably expressed in different tissues; human diploid fibroblasts and leukocytes express all three genes. Random tetramerization ofthese subunits produces various isozymes, which can be distinguished from one another by ion exchange chromatography or by subunit-specific monoclonal antibodies. We have examined 17 somatic cell hybrids established between Chinese hamster cells and human diploid fibroblasts or leukocytes for the expression of L-type subunits of human PFK. As electrophoresis does not distinguish between Chinese hamster PFKs and human PFKs, we used an anti-human L-subunit-specific monoclonal antibody, which does not react with Chinese hamster PFKs. The expression of human L subunits in the hybrids was detected by the enzyme-immunoprecipitation technique using staphylococci bearing protein A as an immunoadsorbent. Twelve out of 17 hybrids expressed human L subunits and retained chromosome 21, as determined by chromosome and isozyme marker analysis, whereas 5 did not express human PFKL and lacked chromosome 21. The mean erythrocyte PFK of seven individuals with trisomy 21 was found to be elevated (147% of normal). A specific increase in L subunits in trisomic erythrocytes was evident chromatographically by a striking increase in L4 species (50%; normal 10%) and immunologically by decreased precipitation with anti-M monoclonal antibody (50%; normal 80%). We conclude from these data that PFKL is located on chromosome 21 and that the previously noted elevation of erythrocyte PFK activity in individuals with trisomy 21 is due to a gene-dosage effect.

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mentioning

confidence: 99%

Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody.

Vora¹,

Francke²

1981

Proc. Natl. Acad. Sci. U.S.A.

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“…2 Normal subjects and those exhibiting Down's syndrome were 5-6 years of age. 3 The salicyluric acid excretion was greater in the normal children at P< 0.05. 4 MeanfSEM.…”

Section: Urinary Metabolitesmentioning

confidence: 81%

Alteration in Metabolism of Ace tylsalicylic Acid in Children with Down's Syndrome: Decreased Plasma Binding and Formation of Salicyluric Acid

Ebadi¹,

Kugel²

1970

Pediatr Res

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ExtractThis paper reports the differences in absorption and distribution in plasma of free and bound salicylate, and the differences in excretion of salicylic and salicyluric acid in the urine of children with Down's syndrome and in control subjects. After oral administration of a single dose of acetylsalicylic acid (35 mg/kg) to normal children, the peak level of salicylic acid in plasma occurred in 2 h and the drug level returned to the base line at approximately 8 h; in children with Down's syndrome, the peak level of salicylic acid occurred in 4 h and the drug level returned to a base line at approximately 16 h. In children with Down's syndrome, the 24-h excretion of salicylate metabolites in the urine indicated a higher level of free salicylic acid (table I) and a lower level of salicyluric acid (tables I1 and 111) when compared with the control group. Although the concentration of salicylate is small in erythrocytes, children with Down's syndrome showed a higher level when compared with their normal counterpart (table IV). The in vitro plasma-binding studies indicated that in comparison with normal subjects, children with Down's syndrome were less capable of binding salicylate (table V). SpeculationPatients with Down's syndrome are a highly abnormal group of individuals because of their morphological, physiological and biochemical aberrations. They are directed and influenced by their abnormalities, one manifestation of which is altered pharmacogenetics. It should be expected that any therapeutic regime must take these differences into consideration and dosage must be calculated not on the basis of body weight but according to the plasma level of the drug or of its active metabolites. Introductioncate that alterations occur in the activity of many enzymes [2,

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“…Trisomy G is most frequently found, whereas translocation is found less frequently. The object of investigation of many authors has been the interdependence between chromosomal anomalies and the changes in metabolism [1,2,3,6,7,14,15]. In children with trisomy G, an increased activity of creatine phosphokinase [15], cholinesterase [1] and enolase [1] has been observed in serum.…”

Section: Introductionmentioning

confidence: 99%

“…The object of investigation of many authors has been the interdependence between chromosomal anomalies and the changes in metabolism [1,2,3,6,7,14,15]. In children with trisomy G, an increased activity of creatine phosphokinase [15], cholinesterase [1] and enolase [1] has been observed in serum. In erythrocytes, an increased activity of galactose-1-phosphate uridyl translerase [3,10], a threefold increase of glucose-6-phosphate dehydrogenase activity [7,14], and a 50% rise of phosphohexokinase [1] have been observed.…”

Section: Introductionmentioning

confidence: 99%

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Efficiency of the Glycolytic Pathway in Erythrocytes of Children with Down's Syndrome

et al. 1972

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ExtractThe intermediates of the glycolytic pathway were investigated in erythrocytes of children with Down's syndrome and the results achieved were compared with those obtained from healthy children of the same age. In the acid-soluble fraction obtained from the erythrocytes, the levels of the intermediates of the glycolytic pathway were determined. The adenine and guanine nucleotides, coenzymes, and inorganic phosphate (Pi) and some other intermediates were examined. The adenine nucleotides: adenosine 5'-monophosphatc (AMP), adenosine o'-diphosphate (ADP), adenosine o'-triphosphate (ATP) and the guanine nucleotide: guanosine fZ-triphosphate (GTP) were determined. The nicotinamide adenine dinueleotide (NAD) and nicotinamide adenine dinueleotide phosphate (NADP), two glycolytic pathway coenzymes, were examined. Hexose diphosphate (HDP) and 2 ,3-diphosphoglyceric acid (2,3-DPG) were tested.Three groups were distinguished after the determination of the karyotype in the children examined: group I, seven children with Down's syndrome and trisomy G (karyotype 47,XX,G + or 47,XY,G +); group II, two children (siblings) with Down's syndrome and G/G translocation (karyotype 46,XX,G -,t(GqGq) +mat or 46,XY, G -,t(GqGq) +mat); and group III, healthy children with a normal karyotype, corresponding to the sex. The results of the biochemical investigations in all of the three groups were compared.Taking the values obtained for the healthy children as standard, a considerable decrease in the levels of ATP and 2 ,3-DPG and an increase in the levels of AMP, GTP, NAD, NADP, Pi, and HDP were noticed in the group of children with Down's syndrome and trisomy G. The ADP concentration was the same as in the control group. The values of some intermediates obtained for the group of mongols with unbalanced translocation G/G were approximately the same as the values obtained for the group of mongols with trisomy G. The 2 ,3-DPG level was just as low as in the mongol group with trisomy G.The results of the calculations, developed by means of the Student test, are statistically significant. Speculation

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Phosphohexokinase Activity of Erythrocytes in Mongolism Another Possible Marker for Chromosome 21

Cited by 69 publications

References 16 publications

Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody.

Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody.

Alteration in Metabolism of Ace tylsalicylic Acid in Children with Down's Syndrome: Decreased Plasma Binding and Formation of Salicyluric Acid

Efficiency of the Glycolytic Pathway in Erythrocytes of Children with Down's Syndrome

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