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Biomedical subjects

E Beutler

Publications and source records attributed to E Beutler.

At least 559 records · Page 31Linked to original sources
PubMed1969

Glutathione reductase: stimulation in normal subjects by riboflavin supplementation.

Glutathione reductase of hemolyzates from clinically normal subjects is activated by the addition of flavin-adenine dinucleotide. One-half maximum stimulation could be achieved by approximately 0.02 micromolar flavin-adenine dinucleotide; prior addition of adenosine triphosphate, adenosine diphosphate, or adenosine mnonophosphate prevented activation. Stimulation of glutathione reductase activity of red cells of normal subjects occurred when they were given 5 milligrams of riboflavin daily for 8 days. The degree of stimulation in vitro by flavin-adenine dinucleotide and in vivo by riboflavin was inversely proportional to dietary intake of riboflavin. The variety of clinical disorders which have been associated with glutathione reductase deficiency may have, as a common denominator, abnormalities in flavin-adenine dinucleotide formation.

Adenine Nucleotides↗
PubMed1969

Cataract produced by tyrosinase and tyrosine systems in rabbitens in vitro.

1. Cataracts were developed by incubating rabbit lenses for 22hr. at 37 degrees in a culture medium containing tyrosine and tyrosinase (EC 1.10.3.1). 2. A 45% diminution in the content of GSH and significant inhibition of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) activity were observed in the cataractous lenses compared with controls. 3. GSSG accumulated in both cataractous and control lenses. Significant amounts of GSSG were transported outward from the cataractous lenses and small amounts from control lenses. 4. Transport of GSSG from rabbit lens incubated in a diffusate of plasma from a naphthalene-fed rabbit was also observed. 5. GSSG was found in the aqueous humour obtained between 2 and 24hr. after feeding of naphthalene to rabbits; subsequently the GSSG in the aqueous humour decreased to almost undetectable amounts in 48hr.; in controls, GSSG was not detectable. 6. A possible mechanism of formation of experimental and senile cataract is briefly discussed.

Animals↗
PubMed1969

The transport of oxidized glutathione from the erythrocytes of various species in the presence of chromate.

1. Erythrocytes from normal and glucose 6-phosphate dehydrogenase-deficient humans were subjected to hydrogen peroxide diffusion to oxidize the GSH. Studies were carried out in the presence and absence of chromate to inhibit glutathione reductase and with or without the addition of glucose. 2. The GSH content of erythrocytes from other species was oxidized by subjecting them to hydrogen peroxide diffusion in the presence of chromate and glucose. 3. Chromate (1.3mm) inhibited glutathione reductase by about 80%, whereas glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, hexokinase, phosphofructokinase and pyruvate kinase were not inhibited. 4. The GSSG formed was transported from the erythrocytes to the medium. 5. The transport rate of GSSG from glucose 6-phosphate dehydrogenase-deficient erythrocytes subjected to hydrogen peroxide diffusion in the presence of chromate was comparable with that from normal and glucose 6-phosphate dehydrogenase-deficient erythrocytes. 6. The rate of transport of GSSG from erythrocytes of various species studied could be ranked: pigeon>rabbit>rat>donkey>man>dog>horse>sheep>chicken>fish.

Adenosine Triphosphate↗
PubMed1969

Mannose metabolism in the human erythrocyte.

The metabolism of mannose by human erythrocytes has been investigated. Phosphorylation of mannose is achieved by an enzyme with electrophoretic mobility on starch gel indistinguishable from the glucose-phosphorylating enzyme. Mannose phosphorylation is competitively inhibited by glucose; glucose phosphorylation is competitively inhibited by mannose. The K(i) values of inhibition are similar to the K(m) values for uninhibited phosphorylation. The normal average mannose-phosphorylating activity was found to be 0.69 U/g of Hb; the normal average glucose-phosphorylating activity was found to be 0.64 U/g of Hb. The ratio of mannose-phosphorylating activity to glucose-phosphorylating activity of a hemolysate prepared from the red cells of a subject with hexokinase deficiency was found to be within the normal range.Phosphomannose isomerase (PMI) activity of the red cells was found to average 0.064 U/g of Hb at its pH optimum of 5.9 with a mannose-6-phosphate (Man-6-P) concentration of 5 mmoles/liter. The enzyme activity in young cells was greater than activity in old cells. When human erythrocytes are incubated with mannose rapid accumulation of Man-6-P occurs, a finding indicating that PMI and not hexokinase is the limiting enzyme in the over-all conversion of mannose to fructose by the red cell. The ratio of mannose utilization to glucose utilization in hexokinase-deficient cells was greater than normal, as has been reported previously. These cells were found to have greatly increased PMI activity, presumably because of their young mean cell age. Consequently, Man-6-P accumulated only approximately one-third as rapidly as normal in hexokinase-deficient cells incubated with mannose. It is believed that the more rapid utilization of mannose relative to glucose by intact hexokinase-deficient cells may be explained on the basis of the regulatory effect of the PMI reaction on the rate of mannose utilization.

Blood Glucose↗
PubMed1969

Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies.

Increases or decreases of red cell glutathione reductase (GR) have been described in connection with many clinical abnormalities. We find that GR activity as measured in hemolysates represents only a portion of the available GR activity. The addition of small amounts of flavin adenine dinucleotide (FAD), but not of flavin mononucleotide or riboflavin, activates the GR of hemolysates. 1 muM FAD results in a maximal activation within 10 min; gradually increasing activation occurs at much lower, for example, 20 mmuM FAD concentrations. Once FAD has activated GR, dilution or dialysis does not reverse activation of the enzyme. Activation of GR by FAD can be inhibited by adenosine triphosphate (ATP), and to a lesser extent by adenosine diphosphate (ADP) and adenosine monophosphate (AMP), if these adenine nucleotides are added before the addition of FAD, but only to a slight extent if FAD is added before the adenine nucleotides. The addition of FAD to GR does not alter its electrophoretic mobility but produces intensification of the bands. The administration of 5 mg of riboflavin daily produces marked stimulation of red cell GR activity within only 2 days. After cessation of riboflavin administration, the GR activity again begins to fall. The degree of stimulation of GR activity by riboflavin is inversely correlated with the level of dietary riboflavin intake. The base line GR activity of normal individuals is directly correlated with the level of dietary riboflavin intake. The previously unexplained variations of glutathione reductase in health and disease must be reevaluated in light of the state of riboflavin nutrition and metabolism of the subject.

Adenine Nucleotides↗