Article

An Hereditary Enzymatic Defect in Erythrocyte Metabolism: Glucose-6-Phosphate Dehydrogenase Deficiency1

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... From mid of the last century, it was accepted that the primary metabolic defect in individuals susceptible to the hemolysis secondary to medicines or to the faba bean consumption (Vicia faba), corresponds to a low activity of the G6PD in erythrocytes 30 . Although the association between the deficiency of G6PD and the non-immune hemolytic and the non-spherocytic anemia 22 is clearly defined, also it is evident its correlation with the hemolysis due to medicines, food and to other events such as infection processes, situation outlined by Vulliamy et al. 31 as the most important cause of hemolysis. ...
... Although the association between the deficiency of G6PD and the non-immune hemolytic and the non-spherocytic anemia 22 is clearly defined, also it is evident its correlation with the hemolysis due to medicines, food and to other events such as infection processes, situation outlined by Vulliamy et al. 31 as the most important cause of hemolysis. Towards 1958, Gross et al. 30 , on one hand and Szeinberg et al. 22 on the other one, determined that the enzymatic deficiency had a hereditary base and suggested that it was bound to sex. The biochemical characterization allowed identifying not less than 442 variants of the deficiency of the enzyme. ...
Article
Full-text available
Glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate pathway and the main intracellular source of reduced nicotidamineadenine nucleotidephosphate (NADPH), involved in diverse physiological processes such as antioxidant defense, (for instance in the erythrocyte) endothelial growth modulation, erithropoyesis, vascularization and phagocitosis. G6PDH deficiency is the most common X-chromosome-linked enzymopathy in human beings. Although it is present in any type cell, its absolute deficiency is incompatible with life. According to WHO, 400 million people are affected by G6PD deficiency in the world but in Colombia, the severe form prevalence is about 3% to 7%. There are no data related to slight and moderate alterations, that also have clinical effects. This paper reviews some G6PD biomolecular aspects, its classification according to activity and electrophoretic mobility, as well as some main clinical aspects related to its activity alteration. Glucosa-6-fosfato deshidrogenasa (G6PD). Respuesta de los hematíes y otras células humanas a la disminución en su actividad RESUMEN La glucosa-6-fosfato deshidrogenasa (G6PD) es la primera enzima de la vía pentosa fosfato y la principal fuente intracelular de nicotidamina adenina dinucleótido fosfato reducido (NADPH), compuesto comprometido en diversos procesos fisiológicos, por ejemplo defensa antioxidante (sobre todo células como los eritrocitos), modulación del crecimiento endotelial, eritropoyesis, vascularización y fagocitosis. La deficiencia de G6PD es la enzimopatía ligada al cromosoma X más común en el ser humano. Si bien se puede presentar en cualquier tipo de célula, su carencia absoluta es incompatible con la vida. Según la OMS, en el mundo hay más de 400 millones de personas afectadas por la deficiencia de la enzima, y para Colombia calculan una prevalencia de la deficiencia severa entre 3% y 7%, pero no se conocen los datos relativos a las alteraciones leves y moderadas, que también tienen efectos clínicos. El presente artículo revisa los aspectos biomoleculares más importantes de la enzima, su clasificación de acuerdo con la actividad y la movilidad electroforética, y también se mencionan algunos aspectos clínicos relacionados con la alteración de su actividad.
... [28] and G6PD (EC: 1.1.1.49) [29][30][31]) ...
Article
The garlic and its principle sulfur compound, diallyl disulphide (DADS) have been claimed to have hypoglycemic action and are beneficial in achieving glycemic control in diabetes mellitus (DM). The actual mechanism how the DADS regulates glucose level in DM is not clearly established though it is known that DADS do influence insulin action probably by improving insulin half-life. A study was undertaken to assess the influence of DADS on glucose utilization in isolated alloxan diabetic liver tissues and to compare DADS action with standard hypoglycemic drug, metformin. The study included four groups: group-1 (normal control liver tissues), group-2 (alloxan diabetic liver tissues), group-3 (Metformin exposed alloxan diabetic liver tissues) and group-4 (DADS exposed alloxan diabetic liver tissues). The liver tissues of groups 3 and 4 were incubated respectively with metformin (4 mg/g liver) and DADS (4 mg/g liver) for one hour at 37°C. The results showed significant raise (p<0.01) in glucose utilization and lactate production in group 4 liver tissues as compared to group 2 suggesting influence of DADS on the glucose utilization promotional effect of DADS which is quite comparable with metformin. The influence of glucose utilization by DADS is through increasing glycolysis in liver as well as its utilization through hexose mono phosphate (HMP) pathway as suggested by increased hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD) activities. Study signifies the use of DADS as adjuvant therapy for glycemic control in DM.
Article
Menschliche Erythrocyten zeigten sich in der Lage, Galaktose zur fermentativen Reduktion von intracellulär erzeugtem Methämoglobin auszunutzen. Erwachsenerythrocyten kamen mit Galaktose, auf 28%, Erythrocyten von 5–20 Tage alten Neugeborenen auf 66% und Nabelschnurerythrocyten auf 89% der mit Glucose erreichten Reduktionsbeschleunigung. Die geringe Atmung der Erythrocyten war bei Neugeborenen und Erwachsenen nicht different, gleichgültig, ob Glucose oder Galaktose als Substrat vorlagen. Durch Zusatz von Methylenblau wurde in beiden Erythrocytenarten die O2-Aufnahme auf das 8fache gesteigert, wenn Glucose anwesend war. Bei Galaktose als Substrat erfolgte durch Methylenblau lediglich bei Neugeborenenerythrocyten eine Steigerung der O2-Aufnahme (auf das 1 1/2fache); bei Erwachsenenerythrocyten sank die O2-Aufnahme ab. Aus den Versuchen ist abzuleiten, daß Erythrocyten von Neugeborenen Galaktose rascher in Glucose umwandeln als Erwachsenenerythrocyten.
Article
6,366 Afro-American infants were screened for G6PD activity. 379 males (11.4&percnt;) and 77 females (2.5&percnt;) were deficient. Confirmation was made by a standard spectrophotometric assay. The results for the male infants in this study are comparable to those found in other studies which accurately establish the deficient male.Copyright © 1980 S. Karger AG, Basel
Article
SINCE the demonstration that red blood cells of almost 10 per cent of American Negroes are deficient in glucose-6-phosphate dehydrogenase1,2, one can suppose that the same defect exists in West Africa. The semi-quantitative test described by Motulsky3 is particularly suitable for a rapid and efficient screening of the male subjects in a given population.
Article
Between March 1961 and March 1962 the activity of G-6-P-D of the erythrocytes from normal and jaundiced newborns was assayed with the aid of a semiquantitative screen test. During the latter half of the investigation, Beutler's GSH Stability Test was also used. The material consisted of normal, non-icteric newborns and of newborns with varying degrees of hyperbilirubinaemia of unknown aetiology. Sixteen out of these had maximal serum bilirubin values of 20 mg/100 ml or more and 62 had serum bilirubin values between 15 and 20 mg/100 ml. No certain case with deficient G-6-P-D activity in the erythrocytes has been found.
Chapter
Genetical StudiesFavismStudies of the Enzyme ItselfCongenital Non-Spherocytic Haemolytic AnaemiaIncidence and DistributionThe FutureReferencesDiscussion
Article
In the past two decades the enormous degree of variability which is characteristic of many human enzymes has unfolded (1,2). Because samples of red blood cells are so easy to obtain they have occupied center stage in the study of enzyme polymorphisms. The investigation of the distribution of various genes for red cell enzymes has been employed to deduce the ebb and flow of human populations. They have been used to establish paternity and as markers in bone marrow transplantation.
Article
SUMMARY1Various glucose-6-phosphate dehydrogenase-deficient pedigrees from the literature violating classical patterns of sex-linked inheritance are reviewed and discussed.2It is suggested that anomalous phenotypes observed in these families may be the result of epistatic reactions between the effects of abnormal sex-linked genes or gene and an autosomal pair.
Article
Es wird ber 3, untereinander nicht verwandte Patienten deutscher Herkunft berichtet, bei welchen als Ursache ihrer hmolytischen Anmie ein Mangel an G-6-PD nachgewiesen werden konnte. Die Untersuchung der Mtter der Patienten bezglich Heterozygotie des Leidens erfolgte durch direkte Fermentbestimmung und durch den morphologischen Enzymnachweis in den einzelnen Erythrocyten. Mit dieser letztgenannten Methode gelingt der Nachweis der Heterozygotie auch in Fllen, wo die Gesamtenzymaktivitt noch im Bereiche der Norm liegt. In einem Falle lieen sich bei der Mutter des Patienten in wiederholten Untersuchungen keine enzymopenischen Zellen nachweisen, so da dort das Vorliegen einer frischen Mutation beim Patienten angenommen werden mu. Das Vorkommen dieser Stoffwechselstrung in der deutschen Bevlkerung wird diskutiert. Durch die zunehmende Imigration aus dem Sden wird sich dieses Gen im Verlaufe der nchsten Jahrzehnte auch bei uns mehr und mehr ausbreiten.Report of three unrelated german patients with G-6-PD deficiency, causing recurrent attacks of haemolytic anaemia. Tests on the mothers for heterozygosity were carried out using the usual determination of enzyme activity as well as morphological enzyme estimation on single red cells. With the latter method it is possible to determinate the heterozygous state, eventhough the enzyme activity in the whole haemolysate lies within normal range. In one mother and her three daughters no pathological cells could be demonstrated in repeated investigations, so it is assumed that a fresh mutation has arisen in her son. The occurence of this metabolic disorder in the german population is discussed. Because of increasing immigration from the south and decreasing gen loss by medical care a wider distribution of this gen would be expected in the next generations.
Article
Glutathion kommt in Biologie und Medizin eine weit gestreute Bedeutung zu. Der Gehalt der meisten pflanzlichen und tierischen Zellen an GSH ist daher sehr hoch. GSH ist wichtig fr die Spaltung von Peroxyden, fr zahlreiche Enzymreaktionen und die Regulation von Stoffwechselvorgngen, fr die Einschleusung von Aminosuren in die Zelle ber den-Glutamyl-Zyklus, fr die Entgiftung vieler Stoffe in der Leber und nach neuesten Untersuchungen auch fr die Freisetzung von Neuro-Transmittersubstanzen. Strungen des Glutathionstoffwechsels knnen zu erheblichen klinischen Erscheinungen, vor allem hmolytischen Anmien, vielleicht auch zentralnervsen Vernderungen fhren.Gluthathione plays an important role in biology and medicine. Most cells of plants and animals contain high concentrations of reduced glutathione and a much smaller amount of oxidised glutathione. GSH is important for several metabolic functions of live cells, e.g. the protection from oxidative stress by peroxides, mediation of enzyme reactions, regulation of metabolic events, transport of amino acids across cell membranes via the gamma-glutamyl cycle, elimination of foreign compounds by GSH-conjugation, release of neurotransmitter substances. Irreversible perturbations of the glutathione metabolism may be the reason for severe clinical symptoms of hemolytic anemia or, perhaps, of central nervous disease.
Article
Es wird ber einen 22jhrigen Japaner mit einer hereditren, nichtsphrozytren hmolytischen Anmie berichtet. Es bestand eine konstante Anmie mit Retikulozytose, Ikterus und Mangel an Glucose-6-Phosphat-Dehydrogenase in den Erythrozyten.Obwohl der Nachweis von Isoenzym an den Erythrozyten des Patienten wegen fehlender Fermentaktivitt nicht gelang, konnte es bei der Mutter, bei den brigen Familienangehrigen und bei Kontrollfllen dem Typ B zugeordnet werden.Cytochemische Untersuchungen ergaben das Vorliegen eines Zellmosaiks in der heterozygoten Mutter des Patienten, jedoch auch im hemizygoten Patienten selber.The case has been presented of a Japanese aged 22 who was suffering from hereditary non-spherocytic haemolytic anaemia. This was a constant type of anaemia associated with reticulocytosis, jaundice, and glucose-6-phosphate dehydrogenase deficiency of the erythrocytes. Although it was not possible, owing to the absence of enzymic activity, to estimate isoenzyme in the patient's erythrocytes, the isoenzyme was assigned, in the patient's mother and in other members of his family, as well as in controls, to the B type. Cytochemical investigations revealed the presence of a cellular mosaic in the patient's mother who was heterozygous, but in the patient, as well, who himself was hemizygous.
Article
This paper presents information about a German family with glucose-6-phosphate-dehydrogenase (G-6-PD) deficiency. A hemizygous carrier of a gene defect suffered from nonspherocytic hemolytic anemia, associated with jaundice and reticulocytosis. The liver was somewhat enlarged, the splen was not palpable. There was transient enhancement of hemolysis after ingestion of green beans and after mental irritation. G-6-PD activity was lowered to less than 1 percent in erythrocytes, to about 10 percent of normal values in plate-letts and leucocytes. The KM-values of the erythrocyte enzyme were depressed approximately by a factor of ten for glucose-6-phosphate and NADPH. Electrophoetic migration of the mutated enzyme was normal. G-6-PD activities in the erythrocytes of the heterozygous mother and daughter of the patient were 44 and 55 percent of the normal values respectively. There were no clinical signs of disease. The defect appearently shows incompletely dominant, X-chromosomal linked inheritance.
Article
Most individuals with G6PD defieciency of the erythrocytes develop hemolytic anemia only after taking drugs or fava beans. The studied patient is a hemizygous carrier of the gene defect. Since birth he suffers from a severe nonspherocytic hemolytic anemia. Hemolysis is enhanced by infections. The activity of the G6PD in the erythrocytes of the patient is diminished to 5 percent of the activity of normal persons. The G6PD of the patient is a variant of the normal enzyme. The affinity of the enzyme to glucose-6-phosphate is depressed by a factor of ten whereas the affinity to NADP is within the normal range. This type of G6PD has not been described til now. The erythrocytes of the heterozygous mother of the patient exhibit an enzyme activity of 57 percent of the activity of normal homozygous persons. The reticulocyte counts of the healthy mother are elevated to about 6 percent. Studies with51Cr-tagged erythrocytes of the patient indicate that liver and spleen are the mean sites of red cell sequestration. There is no difference of body surface activity between these two organs.
Book
Research on abnormal human hemoglobins (protein in blood that carries oxygen), has taught us about the inheritance, biochemistry, and distribution of these traits. This knowledge, coupled with mathematical research using computer models of population genetics, has enabled researchers to marry biological fact and genetic theory. This volume places medical understanding in an evolutionary framework. Using published data on the frequencies of abnormal hemoglobins in the world's populations, Livingston analyzes and interprets these frequencies in the light of world distribution of different forms of diseases such as malaria. He further develops the genetic theory of the evolutionary homeostasis. Livingston discusses the relation of abnormal hemoglobins to endemic malaria and, shows how natural selection pressures explain the known distribution of these traits. Where non-coinciding distributions arise, the book presents other genetic, anthropological, evolutionary, and epidemiological evidence to explain these discrepancies. This classic work remains a useful sourcebook for professors and graduate students of anthropology, genetics, epidemiology, and hematology.
Article
The erithrocitary phosphoglucomutase activity has been studied in 202 subjects: 42 healthy, 72 affected with non tumoral and non hematologic diseases, 88 with malignant tumours of varius type. The phosphoglucomutase activity was found to be, in the 83 per cent of the cancer patients, clearly above the standard deviation limit of the normal and non cancerous patients. It may be admitted that such increase represents one of the many metabolic alterations of the organism affected by cancer.
Chapter
Die in den folgenden Kapiteln besprochenen Anämien stehen in mehr als einer Hinsicht einander so nahe, daß man sie mit Recht in eine Gruppe zusammenfassen kann. Sie sind einheitlich dadurch charakterisiert, daß der Erythrocytenzerfall ganz im Vordergrund steht und damit die Hauptursache der Anämieentwicklung darstellt. Gewiß wird man sagen können, daß der gesteigerte Zerfall der Erythrocyten allein noch keine Anämie bewirkt, wenn das Knochenmark entsprechend dem gesteigerten Zerfall vermehrte Arbeit leistet. Man könnte also zu der Meinung kommen, daß letzten Endes doch eine relative Insuffizienz des Marks an dem Zustandekommen der Anämie beteiligt ist. Diese Markinsuffizienz ist aber bei dieser Anämiegruppe niemals eine absolute, d.h. das Knochenmark leistet bei diesen hämolytischen Anämien niemals weniger, sondern stets mehr als normal, was in der gesteigerten Reticulocytenzahl zum Ausdruck kommt. Aber diese Mehrleistung des Marks genügt bei diesen Anämien nicht, um den Mehrzerfall zu kompensieren. Nur in ganz leichten Fällen dieser Gruppe kommt eine solche Kompensation vor. Dann kommt es aber auch zu keiner Anämieentwicklung, sondern es resultiert trotz der gesteigerten Hämolyse eine normale Erythrocytenzahl. Man spricht in solch seltenen Fällen auch von kompensierter hämolytischer Anämie.
Chapter
Humangenetik ist die Wissenschaft von der Bedeutung der Erbanlagen für den Menschen. Als Genetik des Menschen steht sie mit ihren besonderen Problemen und Methoden neben der Genetik der Tiere und der Pflanzen.
Chapter
During the past few years many of the enzymes catalysing the reactions of the Embden-Meyerhof glycolytic pathway and the pentosephosphate cycle have been demonstrated to occur in multiple forms. The former are, of course, of major interest in connection with the investigation of the mechanism of action of insulin, but at the present time it must be admitted that many of our conclusions are hypothetical. The isoenzymes of the pentose-phosphate cycle are of great importance in the study of hereditary anaemias, both from the diagnostic and genetic points of view. The principal enzymes concerned are shown in the diagram of both pathways illustrated in Fig. 18.
Chapter
The discussion on sex chromosome and X-linked disorders is combined in one chapter because cytogenetic techniques used in diagnosis are common to both. The relatively few sex chromosome disorders occur commonly (see below) but are mostly not associated with fatality or severe mental retardation. In contrast, there are about 200 X-linked disorders (McKusick, 1978), many being fatal and associated with mental retardation or serious defects. Nevertheless, X-linked disorders still serve as an uncommon indication for prenatal diagnosis. (Table I) In our first 2000 prenatal diagnosis cases, 1.3% were in this category, an experience reflected in the Worldwide Survey data (see Chapter 5). One important explanation is that X-linked disorders are seen by physicians in all specialties, e.g., dermatology (Milunsky, 1973) and ophthalmology (Milunsky, 1974, 1977), who have not customarily thought about prenatal diagnosis and avoiding the birth of affected progeny.
Chapter
Obwohl sich die Enzymologie erst seit einem Jahrzehnt mit der Hämatologie befaßt, hat sie in relativ kurzer Zeit schon wesentliche Ergebnisse zur Aufklärung der Pathogenese einiger Bluterkrankungen beigetragen und darüber hinaus noch einige neue hämatologische Erkrankungen entdecken können. Dankbares Objekt für biochemische Untersuchungen sind die menschlichen roten Blutzellen deshalb, weil sie jederzeit leicht gewinnbar sind und einen relativ einfachen Stoffwechsel aufweisen.
Chapter
Die große klinische und genetische Bedeutung des Favismus ist aus der Tatsache ersichtlich, daß die Gesamtzahl der an dieser enzymopenischen hämolytischen Anämie erkrankten Menschen auf etwa 100 Millionen geschätzt wird (2). Dabei schwankt die Morbidität der vornehmlich betroffenen Rassen—Eurasier, Inder, Chinesen, amerikanische Neger und Mittelmeervölker — zwischen 1 und 40% (1, 5, 7, 10, 14, 16). Dagegen ist unseres Wissens das Auftreten einer Fava-Hämolyse bei einer deutschstämmigen Familie bisher nicht bekannt gewesen. Da wir im letzten Jahr erstmals bei einer deutschstämmigen Düsseldorfer Familie eine akute Fava-Hämolyse beobachten konnten, möchten wir kurz über die klinischen, biochemischen und erbbiologischen Untersuchungsbefunde dieser Beobachtung berichten:
Article
In mammals and most other organisms, the first step in the metabolism of glucose is its phosphorylation to glucose-6-phosphate. The metabolic pathways of glucose-6-phosphate utilization can be conveniently divided into two major groups: a) pathways in which glucose is broken down to triose phosphate and will be designated as triose pathways ; and b) pathways that do not yield triose-phosphate and which will be designated here as non-triose pathways. Until fairly recently, it was generally held that glucose is catabolized to triose phosphate solely by the reactions of the classical Embden-Meyerhof (E. M.3) pathway. An alternate pathway of glucose phosphate catabolism in mammalian tissues has been known since about 1930 from Warburg’s discovery of the direct oxidation of glucose-6-phosphate. By 1936, it was known that the aldehyde carbon of glucose-6-phos-phate is decarboxylated to CO2 and a pentose phosphate is formed; and Dickens and Lipmann proposed schemes for glucose oxidation based on these observations. However, little attention was paid to these schemes and the mechanism of this pathway remained obscure until about 1950. Since that time, the detailed operation of this scheme has been elucidated by the work of several laboratories, especially those of Horecker and Racker. The pentose pathway yields CO2 and 1 mole of triose phosphate per mole of glucose, whereas the E. M. pathway yields two moles of triose phosphate, and the subsequent metabolism of the triose phosphate is common to both pathways.
Article
Bei 14 Säuglingen wurde nebeneinander die Stabilität von reduziertem Glutathion und das Ausmaß der Heinzkörperbildung bei Inkubation der Erythrocyten mit Acetylphenylhadrazin geprüft. Bei weniger als 4 Wochen alten Kindern war ein starker Abfall von reduziertem Glutathion festzustellen und eine starke Heinzkörperbildung. Durch Zusatz von Glucose zum Ansatz ließ sich der Absturz von reduziertem Glutathion verhindern, nicht aber die starke Heinzkörperbildung. Bei Neugeborenen ist also die Heinzkörperbildung unabhängig von dem Bestand an reduziertem Glutathion, was im Gegensatz steht zu der Heinzkörperbildung bei Menschen mit genetischem Erythrocytendefekt (Primaquine-Empfindlichkeit, Favismus).
Article
This chapter examines the pathways of metabolism in nucleate and anucleate erythrocytes, with emphasis on erythrocytes of the peripheral blood. The red blood cells of mammals occupy a unique position among cells of plants and animals because they have lost their nuclei by a physiological process. The loss of the nucleus implies the opportunity either to compare cells of the same species during different stages of maturing or to compare anucleate and nucleate cells of corresponding stages. The mature mammal erythrocytes draw their energy requirement exclusively from glycolysis. Depending upon the species involved, the metabolic capacity suffices to maintain the morphological and functional integrity of these highly specialized cells over a period of several months. The mechanism of glycolysis in erythrocytes corresponds to the mechanism in muscles. Glycolysis is considered the most important source of energy for the anucleate mature erythrocytes. It has also been used as an indicator of the viability of preserved erythrocytes. The durability of preserved blood could be extended by the addition of nucleosides. The addition of nucleosides implies a substrate that causes the conversion of inorganic phosphate into an energy-rich bond. This bypasses the hexose phosphorylation and winds up in phosphoglyceraldehyde through the pentose phosphate cycle.
Article
Full-text available
Genetic determinants of sex in placental mammals developed by the evolution of primordial autosomes into the male and female sex chromosomes. The Y chromosome determines maleness by the action of the gene SRY, which encodes a protein that initiates a sequence of events prompting the embryonic gonads to develop into testes. The X chromosome in the absence of a Y chromosome results in a female by permitting the conversion of the embryonic gonads into ovaries. We trace the historical progress that resulted in the discovery that one X chromosome in the female is randomly inactivated in early embryogenesis, accomplishing approximate equivalency of X chromosome gene dosage in both sexes. This event results in half of the somatic cells in a tissue containing proteins encoded by the genes of the maternal X chromosome and half having proteins encoded by the genes of the paternal X chromosome, on average, accounting for the phenotype of a female heterozygote with an X chromosome mutation. The hypothesis of X chromosome inactivation as a random event early in embryogenesis was first described as a result of studies of variegated coat color in female mice. Similar results were found in women using the X chromosome-linked gene, glucose-6-phosphate dehydrogenase, studied in red cells. The random inactivation of the X chromosome-bearing genes for isoenzyme types A and B of glucose-6-phosphate dehydrogenase was used to establish the clonal origin of neoplasms in informative women with leiomyomas. Behind these discoveries are the stories of the men and women scientists whose research enlightened these aspects of X chromosome function and their implication for medicine.
Article
In gewaschenen Erythrocyten von Neugeborenen, Säuglingen, Schulkindern und Erwachsenen wurden die Aktivitäten des Warburgschen Zwischenfermentes, der Glyceraldehydphosphatdehydrogenase, der Lactatdehydrogenase und der Äpfelsäuredehydrogenase sowie der Fructose-1,6-Diphosphat-Aldolase (ALD) und der Glutamat-Oxalacetat-Transaminase (GOT) bestimmt. Während die Aktivitäten der Dehydrogenasen in der Neugeborenenperiode nicht oder nur wenig höher als bei Erwachsenen sind, werden für ALD und GOT in der ersten Lebenszeit erhöhte Werte gefunden. Alle untersuchten Enzymaktivitäten in Erythrocyten zeigen im Schulalter Minimalwerte; diese Befunde werden sowohl bei Bezug auf die Zellzahl als auch bei Bezug auf das Zellvolumen und den Hb-Gehalt erhoben. Nach diesen Befunden kann die für Erythrocyten Neugeborener bekannte Verminderung der Reduktionskapazität für Hämiglobin nicht durch einen Mangel an H-Ionen bedingt sein. Weiterhin weist das Verhalten der Glykolyseenzyme auf das Überwiegen junger Erythrocytengenerationen im ersten Trimenon hin. Diese Befunde bestätigen die biochemisch nachweisbare Alterung roter Blutzellen in vivo.
Article
Studies have been carried out on erythrocytes of cases with past history of acute hemolysis due to Favism, sulpha drugs or PAS. No indication was found of abnormal osmotic or mechanical fragility, electrophoretic mobility of hemoglobin or its amino acid content. Similarly no abnormal glycolytic or catalase activities were detected. Glutathione (GSH) deficiency of erythrocytes was discovered in all cases studied. Similarly, glutathione (GSH) deficiency was a frequent finding among the relatives of affected cases. No such glutathione deficiency could be established in the cases of thalassemia major so far studied, though both patient-groups without any exception belong to the same ethnographic denomination (non-Ashkenazic). This investigation was aided by a grant from the Israel Research Council.
Chapter
This chapter discusses the preparation of nucleoside phosphorylase from calf spleen. The assay method is based on the determination of hypoxanthine formed during the phosphorolysis of inosine b y nucleoside phosphorylase. The hypoxanthine is oxidized to uric acid by xanthine oxidase and may be followed by differential spectrophotometry. One unit of nucleoside phosphorylase is defined as the amount of enzyme which under the above conditions causes an increase in optical density of 0.001 per minute at 293 mμ in the initial rate when read in a cuvette with a light path of 1 cm. In the course of assay, 2600 g. of calf spleen is homogenized in a Waring blendor with 2.5 vol. of cold distilled water and filtered through gauze; the residue is washed with 0.5 vol. of water. The chapter describes an alternative preparation of purine nucleoside phosphorylase from beef liver where an acetone powder extract of the liver is subjected to three successive ethanol precipitations followed by fractionation with ammonium sulfate and silica gel. The purity of the preparation is about 200-fold based on the absorption of the various fractions at 280 mμ. Recently this preparation has been used in the synthesis of 4-amino-5-imidazolecarboxamide riboside.
Article
1. Es wird über einen 30jährigen Iraner mit gesteigerter Hämolyse berichtet, dessen Erythrocyten keine Glucose-6-Phosphatdehydrogenase enthalten. 2. Die glykolytischen und Hämiglobin reduzierenden Fermente sind normal angelegt, der Hämiglobingehalt des Blutes ist nicht erhöht. 3. Der ATP-Gehalt des Vollblutes ist normal. 4. Der erhöhte TPN+-Gehalt der Erythrocyten wird mit dem Ausfall der Glucose-6-Phosphatdehydrogenasereaktion erklärt. 5. Die Hämiglobinreduktion durch Glucose läßt sich durch Toluidinblau nicht steigern. 6. Eine über das Hämiglobinreduktasesystem katalysierte Hämiglobinbildung wurde in den Erythrocyten nicht beobachtet.
Article
The administration of primaquine to six drug-sensitive recipients in daily doses of 30 mg. base resulted in acute hemolysis followed by complete hematological recovery, although drug administration was continued. Studies with Cr51-labeled erythrocytes demonstrated an abrupt decrease in the rate of hemolysis after about a week of drug administration. This was confirmed by clearing of the urine and a return of reticulocyte counts to lower levels. The self-limitation of the hemolysis was shown to he due to a change in the reactivity of the red cell population. The capacity of drug-sensitive volunteers to hemolyze known primaquine-sensitive cells was not altered during long-term drug administration. Prolonged administration of 30 mg. primaquine base daily (50 to 135 days) to six men produced no other evidence of toxicity.
Article
Erythrocytes of uniform age from a primaquine-sensitive individual were labeled with Fe59. When the labeled erythrocytes were 8 to 21 days old, they were insensitive to the hemolytic action of primaquine; 55 days later the same cells were rapidly destroyed when another course of primaquine was administered. This finding further strengthens the relationship between hemolysis by primaquine and hemolysis by certain aniline derivatives. The increased sensitivity of older cells is believed to suggest that a deficiency in one of the red cell enzymes may play a role in primaquine sensitivity.
Article
Studies have been carried out to determine the biochemical nature of the intrinsic defect of primaquine-sensitive erythrocytes. No indication was found that primaquine sensitivity is due to a defect in glycolysis, in catalase activity, in carbonic anhydrase activity, or in cholinesterase activity. Primaquien-sensitive cells are uniformly glutathione (GSH) deficient. Iodoacetic acid and sodium arsenite, two sulfhydryl inhibitors, cause nonsensitive erythrocytes to behave like sensitive erythrocytes in vitro with respect to Heinz body formation.
Article
In the past thirty years a vast body of information has been compiled relating to carbohydrate metabolism. Nevertheless, it is becoming increasingly evident that the elucidation of the metabolic disturbance in diabetes mellitus requires an even more complete knowledge than is presently available of the complex chemical routes followed by glucose in its conversions and interactions with other cell components. In this area of carbohydrate metabolism most gratifying progress has been made with the demonstration of previously unsuspected pathways of glucose utilization. Until rather recently, it was generally believed that the primary, if not the sole, route of glucose breakdown by mammalian tissue was via the Embden-Meyerhof or anaerobic-glycolytic pathway involving the conversion of glucose to pyruvate and lactate and its subsequent oxidation to co2 by the citric acid cycle. Evidence has now accumulated to indicate the existence of at least one new pathway of glucose metabolism, referred to as the pentose phosphate pathway, or the hexose monophosphate oxidative shunt, which may often supplement significantly the anaerobic-glycolytic scheme. Before turning to some of the details and possible significance of this alternate pathway, a brief review of the reactions of glycolysis and the citric acid cycle is desirable.
Article
Four patients are reported who suffered hemobytic anemia after exposure to naphthalene. These were all Negroes; three were male and one female. All the patients were shown by determinations of concentrations of glutathione in whole blood and the glutathione stability test to possess erythrocytes with a defect of glutathione metabolism. One of these patients was a newborn infant to whom naphthalene and its metabolites must have been delivered through the placenta, since both he and his mother had profound hemolytic anemia, but she alone ingested moth balls. In-vitro tests are reported showing the effects of naphthalene and its metabolites on the reduced glutathione of the erythrocytes of the patients. Naphthalene itself is innocous while alpha-naphthoquinone and alpha-naphthol lowered the concentration of reduced glutathione of the erythrocytes in lower dilutions than did beta-naphthoquinone and beta-naphthol. Repeated stability tests done with the erythrocytes of the infant and covering a period of more than 3 months gave support to the hypothesis that the defect in glutathione metabolism expresses itself only in older erythrocytes.
The mechanism of hemolytic anemia induced by nitrofurantoin (Furadantin)
  • E I Kimbro
  • Jr
Kimbro, E. I., Jr. The mechanism of hemolytic anemia induced by nitrofurantoin (Furadantin). Bull. Johns Hopk. Hosp. 1957, 101, 118.
A comparative study of the glycolytic and pentose phosphate pathways in red blood cells of newborns, prematures, infants, and children
  • R T Gross
  • R E Hurwitz
Gross, R. T., and Hurwitz, R. E. A comparative study of the glycolytic and pentose phosphate pathways in red blood cells of newborns, prematures, infants, and children. J. Dis. Child. 1957, 94, 487.
A relationship between human erythrocyte aging in zivo and the activities of glucose-6-phosphate and 6-phosphogluconic dehydrogenases (abstract)
  • P A Marks
Marks, P. A. A relationship between human erythrocyte aging in zivo and the activities of glucose-6-phosphate and 6-phosphogluconic dehydrogenases (abstract). J. clin. Invest. 1957, 36, 913.
A second enzyme abnormality in primaquine sensitive erythrocytes
  • S Schrier
  • R Kellermeyer
  • P Carson
  • A S Alving
Schrier, S., Kellermeyer, R., Carson, P., and Alving, A. S. A second enzyme abnormality in primaquine sensitive erythrocytes. J. Lab. clin. Med. 1957, 50, 951.