Zur transspezifischen Variabilität der Glucose-6-Phosphatdehydrogenase (E.C.: 1.1.1.49) der Primaten

Zusammenfassung Bei subhumanen Primaten können auf Grund ihrer unterschiedlichen Wandergeschwindigkeit in der Elektrophorese fünf verschiedene Glucose-6-Phosphatdehydrogenase-Varianten nachgewiesen werden. Die Verteilung dieser Varianten wurde ermittelt.

---

Transspecific variability of glucose-6-phosphate dehydrogenase (E.C.: 1.1.1.49) in Primates

Summary On the basis of their different electrophoretic mobility five Glucose-6-phosphate dehydrogenase variants are detectable in subhuman Primates: G-6-PD D, G-6-PD C, G-6-PD B, G-6-PD E, G-6-PD F. Their distribution in 428 individuals was estimated.

---

---

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Glucose-6-phosphate dehydrogenase Boston

Summary A hitherto undescribed variant of erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity, G-6-PD Boston, is described in a 24-year-old Caucasian male of Polish-Jewish ancestry. A marked decrease in red cell G-6-PD activity was associated, in this individual, with a compensated hemolytic process. The electrophoretic mobility of the partially purified enzyme on cellulose acetate at pH 9.1 and on starch gel was indistinguishable from normal but the apparent K_m for both G-6-PD (18–21 M) and NADP (1.7–2.2) was significantly decreased. Preliminary evidence supports the concept that G-6-PD Boston may not be extremely rare among this particular population group.     

Frequency of glucose-6-phosphate dehydrogenase, pyruvate kinase and hexokinase deficiency in the Saudi population

The frequencies of glucose-6-phosphate dehydrogenase (G-6-PD), pyruvate kinase (PK) and hexokinase (HK) deficiency were determined in different regions of Saudi Arabia. G-6-PD deficiency was found to range from 0.045 to 0.220 for the male and 0.020 to 0.125 for the female population. The highest frequencies were found to exist in the regions which are endemic to malarial parasite and have high frequencies of sickle cell and thalassaemia genes. Partial deficiencies of PK and HK were encountered in each region, however, no case of complete deficiency of these enzymes was identified. Further investigations are in progress to determine the clinical manifestations of enzyme deficiencies in the Saudi population.     

Frequency of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. A study in Saudi Arabia

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 50 Hb S homozygotes (SS) and 98 Hb S heterozygotes (AS) was determined and compared with the frequency obtained in individuals with normal haemoglobin (AA). The observed number of SS patients with G-6-PD deficiency was significantly greater than the expected value (p less than 0.05). The frequency of G-6-PD deficiency in AA, AS and SS was found to be 0.172, 0.214 and 0.420, respectively. A statistically significant increase of G-6-PD deficiency was apparent in the Saudi sicklers. The possibility that G-6-PD deficiency and Hb S gene interact, influencing the survival of the carriers of these genetic abnormalities, is discussed.     

A new glucose-6-phosphate dehydrogenase variant (G-6-PD Kalyan) found in a Koli family

Summary A new Indian variant of erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) has been detected in a Koli male subject during population genetic studies. The enzyme variant is characterized by mild enzyme deficiency, slow electrophoretic mobility, low K_m for G-6-P, increased utilization of substrate analogues, heat instability and a normal pH optimum curve. From these results this was considered to be a new variant and was designated G-6-PD Kalyan. The family history and routine hematological studies did not reveal any evidence that the G-6-PD Kalyan is associated with any hematological abnormalities or clinical symptoms.     

Characterization of glucose-6-phosphate dehydrogenase in Thailand

Summary Characterization of partially purified eryrhrocyte G-6-PD from 50 enzymedeficient males in 45 unrelated Thai families revealed 6 enzyme variants. Thirty-five subjects in 31 families had G-6-PD variant with normal electrophoretic mobility, slightly low Km G-6-P, normal substrate-analog utilization, normal pH-optimum curve, and slightly increased heat stability. This enzyme variant is called G-6-PD Mahidol.Six subjects had enzyme with fast electrophoretic mobility (106–108% of normal), low Km G-6-P, slightly increased substrate-analog utilization, biphasic pH-optimum curve, and slightly low to normal heat stability. This variant was identical to G-6-PD Canton.Five subjects had G-6-PD with fast electrophoretic mobility (103–106% of normal), low Km G-6-P, very high substrate-analog utilization except for DPN which it did not use as cofactor, markedly biphasic pH-optimum curve and very low heat stability. This variant is called G-6-PD Union (Thai).Two brothers had G-6-PD with normal electrophoretic mobility, low Km G-6-P, slightly increased substrate-analog utilization, biphasic pH-optimum curve and low heat stability. This variant is designated G-6-PD Siriraj.G-6-PD from one patient had slightly fast electrophoretic mobility, increased substrateanalog utilization, especially of DPN, and very low thermal stability. It is called G-6-PD Kan.One subject had G-6-PD with normal electrophoretic mobility, Km G-6-P, pH-optimum curve and heat stability, and increased substrate-analog utilization. This G-6-PD variant is named G-6-PD Anant.G-6-PD Mahidol is far more common than any other known variants in Thailand.

---

Zusammenfassung Eine Charakterisierung von teilweise gereinigtem Erythrocyten-G-6-PD von 50 Männern mit Enzym-Defekt aus 45 nicht miteinander verwandten Thai-Familien ergab 6 Enzym-Varianten. 35 Personen in 31 Familien hatten eine G-6-PD-Variante mit normaler elektrophoretischer Wanderungsgeschwindigkeit, einen leicht verminderten G-6-P-Km-Wert, einer normalen Substratanalog-Verwertung, einer normalen pH-Optimum-Kurve und einer leicht erhöhten Hitze-Stabilität. Diese Enzym-Variante wurde G-6-PD Mahidol genannt.Sechs Personen hatten ein Enzym mit rascher elektrophoretischer Wanderung (106–108% der Norm), niedrigem Km für G-6-P, leicht erhöhter Substrat-Verwertung, einer biphasischen pH-Optimum-Kurve und normaler bis leicht erniedrigter Hitzestabilität. Diese Variante ist identisch mit G-6-PD Canton.Fünt Personen hatten G-6-PD mit rascher elektrophoretischer Wanderung (103–106%), niedrigem Km G-6-P, sehr hoher Substratanalog-Verwertung—mit Ausnahme von DPN, das nicht als Cofactor wirkte—, einer stark biphasischen pH-Optimum-Kurve und sehr geringer Hitze-Stabilität. Diese Variante wurde als G-6-PD Union (Thai) bezeichnet.Zwei Brüder hatten ein G-6-PD mit normaler elektrophoretischer Wanderung, niedrigem Km G-6-P, leicht erhöhter Substratanalog-Verwertung, einer biphasischen pH-Optimum-Kurve und geringer Hitze-Stabilität. Diese Variante erhielt den Namen G-6-PD Siriraj.G-6-PD eines Patienten hatte eine leicht erhöhte elektrophoretische Wanderungsgeschwindigkeit, eine erhöhte Substratanalog-Verwertung, besonders für DPN, und eine sehr geringe Hitze-Stabilität (G-6-PD Kan).Eine Person zeigte ein G-6-PD mit normaler elektrophoretischer Wanderungsgeschwindigkeit, Km G-6-P pH-Optimum-Kurve und Hitze-Stabilität. Nur die Substratanalog-Verwertung war erhöht. Diese Variante wurde G-6-PD Anant gennant.G-6-PD Mahidol ist die bei weitem häufigste Variante in Thailand.

---

---

This investigation received financial support from the World Health Organization.     

Aspects of sickle cell gene in Saudi Arabia—interaction with glucose-6-phosphate dehydrogenase deficiency

Summary Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell haemoglobin (Hb S) are red cell genetic abnormalities that occur at a high frequency in several areas of the world including several areas of Saudi Arabia. Genetic and clinical interactions between these two disorders are reported to occur in some populations.In the present investigations, samples from affected individuals were studied for the prevalence of G-6-PD deficiency and Hb S genes. The results of haematological parameters and common clinical findings in the Hb S homozygotes with and without G-6-PD deficiency are presented and the possibility that the two conditions interact beneficially is discussed.     

Glucose-6-phosphate dehydrogenase in the population of northern Thailand: Evidence for two common electrophoretic variants with deficient enzyme activity

Summary Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, identified by a dye decolorization test, was found in 101 (12.5 percent) of 811 male subjects from northern Tailand. Blood samples from 169 subjects with normal G-6-PD activity and from all 101 subjects with G-6-PD deficiency were examined by electrophoresis on cellulose acetate gel with the following results: In all samples with normal G-6-PD activity the enzyme had the electrophoretic mobility of type B G-6-PD. 73 of the 101 G-6-PD deficient samples had the same mobility and are therefore probably identical with the common Mediterranean variant B-. 16 of the 101 deficient samples contained an electrophoretically fast G-6-PD, and 1 sample a slow variant. In 11 deficient samples the enzyme could not be made visible. Kinetic studies on crude hemolysates suggest that the fast variant has a higher mean activity and heat stability in comparison to the B- variant.Established and supported by Stiftung Volkswagenwerk, Hannover.     

Glutathione reductase deficiency in association with sickle cell and thalassaemia genes in Saudi populations

Glutathione reductase (GR) deficiency is reported to occur with a variable frequency in some populations of the world. In this study, the populations of two regions of Saudi Arabia which have a high frequency of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, were screened for GR deficiency. Studies were also carried out to investigate the frequency of GR deficiency with other genetic blood disorders. The frequencies of complete GR deficiency were 0.0065 and 0.006, while those of partial deficiency were 0.146 and 0.074 in Al-Hafouf and Khaiber, respectively. GR deficiency was encountered in combination with the sickle gene, the G-6-PD deficiency gene and the thalassaemia gene in both regions. Individuals with GR deficiency showed slightly reduced haematological parameters. In thalassaemic/GR-deficient subjects, mean cell volume and mean cell haemoglobin were low, while in sickle cell anaemia patients with GR deficiency the haematological parameters were higher than in sickle cell anaemia patients without GR deficiency.     

Human platelet glucose-6-phosphate dehydrogenase. Total purification, kinetic studies and relationship with enzyme from other blood cells.

Human platelet G-6-PD has been highly purified, to homogeneity, and its kinetic, electrophoretic and immunological characteristics have been studied. Platelet G-6-PD differs from erythrocyte or leukocyte enzymes by an increased Michaelis constant for G-6-P and a slow activity at the acid pHs. By electrofocusing only a main active band (band a) of platelet G-6-PD was found. The incubation at 37 degrees C in the presence of NADP+ and dithiothreitol normalize Km-G-6-P of platelet G-6-PD; the incubation with boiled and ultrafiltered leukemic granulocyte extracts led to an anodisation of G-6-PD active forms, a decrease of the molecular specific activity and a further increase of Km-G-6-P; these last modifications are the same as those undergone by G-6-PD incubated in crude extracts of normal or leukemic granulocytes.     

Characteristics of a new abnormal variant of G-6-PD in human red cells.

Kinetic and electrophoretic properties were studied in 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G-6-PD) from red cells of donors and patients with hemolytic anemia induced by G-6-PD deficiency. In abnormal variant of G-6-PD isolated from red cells of a patient with hemolytic anemia which had not before been described in the literature was found. The abnormal variant differs from the normal enzyme by a decreased Michaelis constant for G-6-P and NADP, by increased utilization of substrate-analogues (2-deoxy-G-6-P and deamino NADP in particular), by low heat stability, the character of pH dependence, and by the appearance of one band of G-6-PD activity during electrophoresis in polyacrylamide gel. The isolated abnormal variant of G-6-PD has been called "Kremenchug" according to the origin of the patient.     

Glucose-6-?hosphate dehydrogenase deficiency,haptoglobin and hemoglobin variants in dogs

Blood samples from 31 male and 34 female, adult, healthy dogs of different breeds were studied for erythrocytic G-6-PD activity. The hemolysates were also studied electrophoretically for G-6-PD, 6-PGD, and hemoglobin variants. Most of the plasma samples revealed a human Hp 1–1 type of band while three samples had an additional fast-moving band that disappeared on addition of an excess of hemoglobin and two samples were ahaptoglobinemic. G-6-PD deficiency was detected in eight samples, and it was more frequent in males than in females. The implications of G-6-PD deficiency with no difference in the electrophoretic pattern and of ahaptoglobinemia are discussed with respect to different genetic and clinical possibilities.     

Effects of cadmium and zinc ions on purified lamb kidney cortex glucose-6-phosphate dehydrogenase activity

Glucose-6-phosphate dehydrogenase (G-6-PD) is the first enzyme in the pentose phosphate pathway. Cadmium is a toxic heavy metal that inhibits several enzymes. Zinc is an essential metal but overdoses of zinc have toxic effects on enzyme activities. In this study G-6-PD from lamb kidney cortex was competitively inhibited by zinc both with respect to glucose-6-phosphate (G-6-P) and NADP+ with Ki values of 1.066 +/- 0.106 and 0.111 +/- 0.007 mM respectively whereas cadmium was a non-competitive inhibitor with respect to both G-6-P and NADP+ Ki values of 2.028 +/- 0.175 and 2.044 +/- 0.289 mM respectively.     

Glucose-6-phosphate dehydrogenase deficiency in Saudi Arabia. A study in Al-Ula

This paper reports the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the male and female population of A1-Ula in the northwestern province of Saudi Arabia. The frequency of G6PD deficiency in the male population was 0.098 and in the females it was 0.028. This frequency is significantly lower than those reported for other malaria endemic regions in Arabia. The population was further subgrouped on the basis of their haemoglobin phenotypes and the highest frequency of G6PD deficiency was obtained in male Hb S heterozygotes followed by the male Hb S homozygotes. Phenotyping of G6PD revealed the presence of G6PD-Mediterranean, G6PDA+, G6PDA- and G6PD Mediterranean-like, and the frequency of these variants in Al-Ula was different from those reported in other regions of Saudi Arabia.     

Glucose-6-phosphate dehydrogenase isoenzymes in root growth zones ofVicia faba

The specific activity of glucose-6-phosphate dehydrogenase (G-6-PD) in growth zones ofVicia faba roots is increasing with cell maturation and differentiation. Changes in the total activity of G-6-PD are not associated with a change in the number of G-6-PD isoenzymes. Five G-6-PD isoenzymes were found in all root growth zones. Some differences were found in the activity of individual isoenzymes.     

Electrophoretic patterns of glucose metabolizing enzymes and acid phosphatase in mouse and human neuroblastoma cells

The electrophoretic patterns of glucose metabolizing enzymes and acid phosphatase in mouse and human neuroblastoma cells were investigated. Mouse neuroblastoma cells had one band of lactate dehydrogenase (LDH) and two bands of acid phosphatase, whereas human neuroblastoma cells had five bands of LDH and one band of acid phosphatase. Glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (6-PGD) were expressed as a single band in both mouse and human neuroblastoma cells. The electrophoretic pattern of LDH was similar in mouse neuroblastoma cells grown in culture or in vivo. The electrophoretic band of G-6-PD in mouse neuroblastoma cells grown in vivo appeared to be less dense than that observed in cells grown in culture; however, the reverse was true for 6-PGD. Among all enzymes examined, only the electrophoretic pattern of G-6-PD in cAMP-induced “differentiated” mouse neuroblastoma was different in comparison to control cells.     

Glucose-6-phosphate dehydrogenase deficiency and sickle cell disease in Brazil.

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was determined in 54 male patients with sickle cell diseases: 31 sickle cell anemia (SS), 14 sickle cell hemoglobinopathy (SC) and 9 HbS/beta-thalassemia (S/B-thal) by a combination of quantitative assay, fluorescent spot test and electrophoresis. Of the 54 patients tested, 7 were found to be G-6-PD deficient (G-6-PD-) (3 SS, 3 SC and 1 S/B-thal) and 47 G-6-PD normal (G-6-PD+) (6 G-6-PD A and 41 G-6-PD B). All the deficient patients were G-6-PD A-. The frequency of G-6-PD deficiency did not differ significantly from that observed in the general population. Compared to patients who were not G-6-PD-, there were no significant differences in the hemoglobin concentration and reticulocyte count in patients with sickle cell diseases who were G-6-PD-.     

Leucocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity in G-6-PD deficient Chinese

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied for erythrocyte G-6-PD deficiency using 49 hemizygous males, 16 heterozygous females, and 19 normal controls. The mean G-6-PD activity in leucocytes of the affected neonates (9.2 +/- 5.4 units) and the children (11.2 +/- 5.3 units) were significantly lower than those of normal newborns (22.9 +/- 5.1 units, P less than 0.01). Seventy percent of the effected newborns and 58% of the children with G-6-PD deficiency had the leucocyte enzyme activity of less than 13 IU/10(9)WBC. The leucocyte enzyme activity (14.6 +/- 8.6 units) of 16 heterozygous G-6-PD deficient mothers was also lower than that of normal controls (23.1 +/- 7.0 units). The present study thus concludes that, in G-6-PD deficient Chinese, the enzyme defect is demonstrable not only in erythrocytes but also in leucocytes.     

Activities of Glucose-6-phosphate, 6-phosphogluconate,and Isocitrate Dehydrogenases from Leishmania donovani Cultivated at 25 and 37 C*

SYNOPSIS. The activities of glucose-6-phosphate dehydrogenase (G-6-PD) (EC No. 1.1.1.49), 6-phosphogluconate dehydrogenase (PGD) (EC No. 1.1.1.44), and isocitrate dehydrogenase (ICD) (EC No. 1.1.1.42) from promastigotes of Leishmania donovani strain 3S grown at 25 C in modified Tobie's (mT) medium and from promastigotes of the 37 C-adapted substrain of this strain cultivated in the mT at 37 C were assayed at 25 and 37 C. At 25 C ICD from both the strain and the substrain had the highest, and PGD, the lowest activity; the activity of G-6-PD was intermediate, but much closer to that of ICD. Irrespective of the temperature of the assay, the activities of G-6-PD and ICD from the 37 C substrain were significantly higher than those of these enzymes from the parental strain; however, the activity of PGD from the 25 C strain was slightly higher than that of this dehydrogenase from the 37 C-adapted stock. No significant activity losses of G-6-PD and ICD from either the strain or the substrain were noted after incubation of the extracts in the presence of 0.25 M sucrose at 37 C for 2 hr. PGD was unstable in such extracts, but it could be rendered stable by the addition of 4 mM 6-phosphogluconate. G-6-PD was the least and ICD the most dependent on Mg²⁺ ions. In the 15–25 C range, the Q₁₀ values of the enzymes from the 25 C strain were 2.83, 2.5, and 2.63 for G-6-PD, PGD, and ICD, respectively. These values for the respective enzymes in the 25–35 C range were 2.06, 1.67, and 1.62. The Q₁₀ values of the enzymes from the 37 C substrain in the 15–25 C range were 2.06 for G-6-PD, 3.25 for PGD, and 2.77 for ICD; in the 25–35 C range, the corresponding values were 1.67, 1.46, and 1.83. Cultivation of the 37 C substrain at 25 C was accompanied by a drop in G-6-PD and ICD activities.     

Influence of L-thyroxine upon enzymatic activity in the renal tubular epithelium of the rat under normal conditions and mercury-induced lesions. II. Histochemical studies of lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, unspecific esterase, and glucose-6-phosphate dehydrogenase.

Mercury-induced renal tubular lesions in the rat present histochemically with a decrease of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G-6-PD), and unspecific esterase (UE), but with an increase of lactate dehydrogenase (LDH), indicating a drop of energy supply as well as a switch from oxidative to glycolytic energy production. L-thyroxine has the same effect on SDH, G-6-PD, and LDH, but an inverse effect on MDH and UE, pointing to stimulation of gluconeogenesis. However, administration of L-thyroxine to animals which have been submitted to sublimate intoxication even further decreases the MDH and UE activity while raising or partly restoring the activity of LDH, SDH, and G-6-PD. This observation is interpreted as an attempt of the damaged epithelial cell, as the gluconeogenesis ceases, to gain relatively more energy supply for the benefit of the vitally indispensable tubular Na+ reabsorption.