Intermediary Metabolites and Adenine Nucleotides in Leucocytes of Children with Protein–Calorie Malnutrition

Yoshida, Takashi; Metcoff, Jack; Frenk, Silvestre; Peña, Carmen de la

doi:10.1038/214525a0

Cited by 33 publications

(8 citation statements)

References 11 publications

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“…The changes were similar to those previously noted for PCM [20,21]. They were consistent with the earlier observation of Edmonson et al [7] of a reduction in the ouabain-sensitive activity in leukocytes of chronically uremie, hemodialyzed patients.…”

Section: Cellular Malnutrition In Uremiasupporting

confidence: 92%

“…Later, using polymorphonuclear leukocytes isolated from blood, we found that the enzyme and metabolite patterns in malnourished children were similar to those in muscle, and the activity constant of the important energy-regulating enzyme adenylate kinase also was reduced in children with Kwashiorkor [20,21]. Adenylate kinase catalyzes the nucleotide equilibrium ATP + AMP = 2ADP.…”

Section: Equilibrium Constant Of Adenylate Kinasementioning

confidence: 85%

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Malnutrition at the cellular level in uremia: a new frontier for research.

Metcoff¹

1986

Journal of the American College of Nutrition

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Previously reported studies showed that protein-calorie malnutrition (PCM) in children is associated with significant alterations in muscle cell composition, characterized by increased cell water and Na, with decreased concentrations of K, Mg, and some glycolytic and citric acid cycle metabolites. In PCM, the i.c. H2O and levels of Na and K were significantly related, by multiple regression analysis, to the combined set of simultaneously measured levels of cell metabolites, phosphoenolpyruvate, pyruvate, alpha-ketoglutarate, and oxaloacetate. Cell bioactivities also were affected by PCM. Activities of the enzymes pyruvate kinase and malic and isocitric dehydrogenases were significantly reduced in muscle homogenates of PCM children. Kinetic analysis of pyruvate kinase indicated an 8-10-fold reduction in maximal velocity of the enzyme, consistent with a reduction in enzyme protein. Additionally, reduced levels of ATP and the equilibrium constant of the adenylate kinase system were observed in leukocytes of PCM children. Alterations in the activity of the energy-dependent Na pump have been noted by others in association with the accumulation of i.c. Na in severe malnutrition. Neither protein synthesis nor amino acid pools was measured in these previously reported studies. Recent data from several laboratories show that the "profiles" of i.c. and plasma amino acids are very different, both in uremics and in control subjects. In control subjects, with leukocytes as the cell model, the level of protein synthesis can be predicted by multiple regression analyses from simultaneously measured levels of plasma or i.c. amino acids. Intracellular amino acids are better predictors. Of 19 intracellular amino acids, a combination of five accounted for 54% of the variance in protein synthesis in normal, healthy adults. Levels of these predictor cell amino acids can, in turn, be predicted by different combinations of apparently unrelated plasma amino acids. In adult uremic patients stabilized by hemodialysis, with leukocytes as the cell model, levels of ATP, energy charge, adenylate kinase and pyruvic kinase activities were reduced. Others have reported increased i.c. water and Na contents, and impaired Na pump activity. Cell levels of methionine and the branched-chain amino acids, valine, leucine, and isoleucine, and protein synthesis also were significantly reduced. By multiple regression analysis, the observed levels of protein synthesis and energy charge in the hemodialyzed uremic patients were largely accounted for by different combinations of intracellular amino acid than in healthy subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Cellular Malnutrition In Uremiasupporting

confidence: 92%

Section: Equilibrium Constant Of Adenylate Kinasementioning

confidence: 85%

Malnutrition at the cellular level in uremia: a new frontier for research.

Metcoff¹

1986

Journal of the American College of Nutrition

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“…The values obtained in this study are therefore within the same range, though slightly higher than those of Yoshida & Metcoff (1967).…”

Section: Leucocyte (Na+ + K+)-atpase Activity and Atp Contentsupporting

confidence: 65%

“…In a study of leucocyte ATP in children with malnutrition, Yoshida & Metcoff (1967) found the control value for leucocyte ATP to be 4-82 f 0.67 pmol/g of protein.…”

Section: Leucocyte (Na+ + K+)-atpase Activity and Atp Contentmentioning

confidence: 96%

A Study In Vitro of the Sodium Pump in Fulminant Hepatic Failure

Alam¹,

Poston

Wilkinson

et al. 1978

Clinical Science

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1. The mechanism underlying the raised leucocyte sodium content in fulminant hepatic failure was studied by measurement of sodium fluxes, (Na+ + K+)-dependent adenosine triphosphatase activity, and leucocyte ATP content. 2. The rate constant for sodium efflux in the leucocytes was significantly reduced, and attributable to reduced activity of the enzyme (Na+ + K+)-ATPase. Leucocyte ATP content was not significantly different from that of control cells. 3. Incubation of cells from patients in the sera of normal subjects resulted in a reversal of these changes. Inhibition of the leucocyte sodium efflux rate constants and (Na+ +K+)-ATPase of normal cells was achieved by incubation in sera from patients. 4. We suggest that the raised sodium content of leucocytes in fulminant hepatic failure is attributable to a defective sodium pumping mechanism, possibly due to a circulating toxin.

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“…Leukocytes from infants with severe PCM recently were shown to have decreased contents of pyruvate, lactate, oxaloacetate, and ATP. The adenylate kinase system also seemed to be im paired since the constant for this system (ATP XAM PjADp2) was signifi cantly reduced compared to that of controls (193) . The metabolite changes might be consistent with impaired glycolysis at the pyruvic kinase step.…”

Section: Growth Of the Newbornmentioning

confidence: 90%

Biochemical Effects of Protein-Calorie Malnutrition in Man

Metcoff¹

1967

Annu. Rev. Med.

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Intermediary Metabolites and Adenine Nucleotides in Leucocytes of Children with Protein–Calorie Malnutrition

Cited by 33 publications

References 11 publications

Malnutrition at the cellular level in uremia: a new frontier for research.

Malnutrition at the cellular level in uremia: a new frontier for research.

A Study In Vitro of the Sodium Pump in Fulminant Hepatic Failure

Biochemical Effects of Protein-Calorie Malnutrition in Man

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