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

Abstract

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

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

“…The following studies give directly group means (M), standard deviations (SD) and sample sizes (N): Helguera et al ( 2013 ), Bayer and McCoy ( 1974 ), Bartels ( 1971 , Knull et al ( 1978 ), Puukka et al ( 1982 ), Kedziora et al ( 1972 ), Nelson and Benson ( 1972 ), de Asua et al ( 2014a , b ), Lejeune et al ( 1992 ), Nura et al ( 2008 ), Infantino et al ( 2011 ), Zitnanova et al ( 2004 ), de Sousa et al ( 2015 ); Howell et al ( 1973 ); Kaufman and O’Brien ( 1967 ), Campos et al ( 2010 ), Yates et al ( 1990 ), Zaki et al ( 2017 ), Coppus et al ( 2007 ), Pogribna et al ( 2001 ) and Miles et al ( 2007 ).…”

“…The oxidation process results in free energy production that can be stored in high-energy bonds within molecules such as nucleoside triphosphate, phosphoenolpyruvate, carbamoyl phosphate, 2,3-bisphosphoglycerate, phosphoarginine, or phosphocreatine (Bonora et al 2012 ). Kedziora and his coworkers have reported decreased levels of 2,3-diphosphoglyceric acid, and increased content of AMP, GTP, NAD + , and NADP + (Kedziora et al 1972 ). Our meta-analysis performed on ATP, ADP and AMP levels revealed statistically significant changes.…”

Pathogenesis of mental deficiency in trisomy 21

“…IMP dehydrogenase can also be modified by a specific inhibitor: mycophenolic acid ( N PA) [791, a natural modulator: 2-3 diphosphoglycera1.e (2)(3) [771 and reverse triiodotyrosine (r'Il3). In trisomy 21 erythrocytes, 2-3 DPG is low [63,64,81], its synthesis is under thyroxin command [125.1261, and rT3 is also low in trisomy 21 [76]. Pre1iminar:r data show a very tight correlation between the effects 3f these 3 products when tested on the lymphocytes of tne same patient.…”