scholarly journals Regulation of the pentose phosphate cycle

1974 ◽  
Vol 138 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Leonard V. Eggleston ◽  
Hans A. Krebs
Keyword(s):  
Reductase Activity ◽  
Pentose Phosphate ◽  
Pentose Phosphate Cycle ◽  
Rate Limiting Step ◽  
Dehydrogenase Reaction ◽  
Fine Control ◽  
Liver Homogenates ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Rate Limiting ◽  
Gssg Reductase

1. A search was made for mechanisms which may exert a `fine' control of the glucose 6-phosphate dehydrogenase reaction in rat liver, the rate-limiting step of the oxidative pentose phosphate cycle. 2. The glucose 6-phosphate dehydrogenase reaction is expected to go virtually to completion because the primary product (6-phosphogluconate lactone) is rapidly hydrolysed and the equilibrium of the joint dehydrogenase and lactonase reactions is in favour of virtually complete formation of phosphogluconate. However, the reaction does not go to completion, because glucose 6-phosphate dehydrogenase is inhibited by NADPH (Neglein & Haas, 1935). 3. Measurements of the inhibition (which is competitive with NADP+) show that at physiological concentrations of free NADP+ and free NADPH the enzyme is almost completely inhibited. This indicates that the regulation of the enzyme activity is a matter of de-inhibition. 4. Among over 100 cell constituents tested only GSSG and AMP counteracted the inhibition by NADPH; only GSSG was highly effective at concentrations that may be taken to occur physiologically. 5. The effect of GSSG was not due to the GSSG reductase activity of liver extracts, because under the test conditions the activity of this enzyme was very weak, and complete inhibition of the reductase by Zn2+ did not abolish the GSSG effect. 6. Preincubation of the enzyme preparation with GSSG in the presence of Mg2+ and NADP+ before the addition of glucose 6-phosphate and NADPH much increased the GSSG effect. 7. Dialysis of liver extracts and purification of glucose 6-phosphate dehydrogenase abolished the GSSG effect, indicating the participation of a cofactor in the action of GSSG. 8. The cofactor removed by dialysis or purification is very unstable. The cofactor could be separated from glucose 6-phosphate dehydrogenase by ultrafiltration of liver homogenates. Some properties of the cofactor are described. 9. The hypothesis that GSSG exerts a fine control of the pentose phosphate cycle by counteracting the NADPH inhibition of glucose 6-phosphate dehydrogenase is discussed.

scholarly journals Regulation of the pentose phosphate cycle Cofactor that controls the inhibition of glucose-6-phosphate dehydrogenase by NADPH in rat liver

1986 ◽  
Vol 239 (3) ◽  
pp. 553-558 ◽  
Author(s):  
M Nogueira ◽  
G Garcia ◽  
C Mejuto ◽  
M Freire
Keyword(s):  
Ion Exchange ◽  
Rat Liver ◽  
Pentose Phosphate Pathway ◽  
Reductase Activity ◽  
Gel Filtration ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Pentose Phosphate ◽  
Glutathione Reductase Activity ◽  
Glucose 6 Phosphate Dehydrogenase

A cofactor of Mr 10(4), characterized as a polypeptide, was found to co-operate with GSSG to prevent the inhibition of glucose-6-phosphate dehydrogenase by NADPH, in order to ensure the operation of the oxidative phase of the pentose phosphate pathway, in rat liver [Eggleston & Krebs (1974) Biochem. J. 138, 425-435; Rodriguez-Segade, Carrion & Freire (1979) Biochem. Biophys. Res. Commun. 89, 148-154]. This cofactor has now been partially purified by ion-exchange chromatography and molecular gel filtration, and characterized as a protein of Mr 10(5). The lighter cofactor reported previously was apparently the result of proteolytic activity generated during the tissue homogenization. The heavier cofactor was unstable, and its amount increased in livers of rats fed on carbohydrate-rich diet. Since the purified cofactor contained no glutathione reductase activity, the involvement of this enzyme in the deinhibitory mechanism of glucose-6-phosphate dehydrogenase by NADPH should be ruled out.

Blood glutathione status during exercise: effect of carbohydrate supplementation

1993 ◽  
Vol 74 (2) ◽  
pp. 788-792 ◽  
Author(s):  
L. L. Ji ◽  
A. Katz ◽  
R. Fu ◽  
M. Griffiths ◽  
M. Spencer
Keyword(s):  
Prolonged Exercise ◽  
Reduced Glutathione ◽  
Reductase Activity ◽  
Work Load ◽  
Inhibitory Effects ◽  
Carbohydrate Supplementation ◽  
Glutathione Status ◽  
Exercise Effect ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Gssg Reductase

Blood glutathione status and activities of antioxidant enzymes have been investigated during prolonged exercise with or without carbohydrate (CHO) supplementation. Eight subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [134 +/- 19 (SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with CHO ingestion during exercise. Blood reduced glutathione (GSH) concentration increased from 0.55 +/- 0.05 mM at rest to 0.77 +/- 0.09 mM after 120 min of exercise during CON (P < 0.01) but remained constant during CHO exercise. Blood glutathione disulfide (GSSG) levels were unchanged during CON and CHO exercise. Blood GSH + GSSG content and GSH/GSSG ratio were also significantly (P < 0.05) elevated during CON but not during CHO exercise. The increases in GSH and GSH + GSSG in CON were associated with decreases in plasma glucose and insulin levels. Activities of blood GSH peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase were significantly increased during the CHO exercise, whereas only GSSG reductase activity was elevated during the CON ride. It is concluded that blood GSH increases during prolonged exercise and that CHO supplementation may prevent blood GSH increase possibly because of its inhibitory effects on hepatic hormonal releases, which stimulate GSH output.

scholarly journals The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver

1969 ◽  
Vol 111 (5) ◽  
pp. 713-725 ◽  
Author(s):  
F. Novello ◽  
J. A. Gumaa ◽  
Patricia McLean
Keyword(s):  
Diabetic Rats ◽  
Pentose Phosphate ◽  
Hexokinase Activity ◽  
Transketolase Activity ◽  
Control Value ◽  
Phosphogluconate Dehydrogenase ◽  
Pentose Phosphate Cycle ◽  
Oxidative Reactions ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Adrenalectomized Rats

1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ‘overshoot’ effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30–40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine–zinc–insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine–zinc–insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.

The effects of tunicamycin, mevinolin and mevalonic acid on HMG-CoA reductase activity and nuclear division in the myxomycete Physarum polycephalum

1989 ◽  
Vol 92 (3) ◽  
pp. 341-344
Author(s):  
W. Engstrom ◽  
O. Larsson ◽  
W. Sachsenmaier
Keyword(s):  
Physarum Polycephalum ◽  
Nuclear Division ◽  
Reductase Activity ◽  
Mevalonic Acid ◽  
Minor Effect ◽  
Hmg Coa Reductase ◽  
Rate Limiting Step ◽  
Coa Reductase ◽  
A Minor ◽  
Rate Limiting

The effects of two inhibitors of 3-hydroxy 3-methyl glutaryl-coenzyme A reductase (tunicamycin and mevinolin) on nuclear division in the myxomycete Physarum polycephalum were examined. Tunicamycin exerted a minor effect on division in synchronized cultures, whereas mevinolin delayed the second, third and fourth nuclear divisions with increasing efficiency. Mevinolin also appeared to be the more potent inhibitor of HMG-CoA reductase, which catalyses the rate-limiting step in the biosynthesis of cholesterol and other isoprene derivatives. These effects of mevinolin could be partially reversed by the addition of mevalonate, suggesting that mevinolin exerts its inhibitory effects on Physarum nuclear division by decreasing the activity of HMG-CoA reductase.

scholarly journals Regulation of the oxidative phase of the pentose phosphate cycle in mussels

1978 ◽  
Vol 170 (3) ◽  
pp. 577-585 ◽  
Author(s):  
S Rodriguez-Segade ◽  
M Freire ◽  
A Carrion
Keyword(s):  
Inorganic Ions ◽  
Pentose Phosphate ◽  
Oxidized Glutathione ◽  
Phosphogluconate Dehydrogenase ◽  
Pentose Phosphate Cycle ◽  
Intracellular Concentrations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Substrate Concentrations

1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verifed. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions.

scholarly journals The effects of force-feeding on enzymes of the liver, kidney, pancreas and digestive tract of chicks

1974 ◽  
Vol 32 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Zafrira Nitsan ◽  
Y Dror ◽  
I. Nir ◽  
Niva Shapira
Keyword(s):  
Digestive Tract ◽  
Food Consumption ◽  
Digestive Enzymes ◽  
Xanthine Dehydrogenase ◽  
Pentose Phosphate ◽  
Absolute Weight ◽  
Pentose Phosphate Cycle ◽  
Force Feeding ◽  
Specific Activities ◽  
Glucose 6 Phosphate Dehydrogenase

1. Force-feeding of young chicks for 15 d increased kidney arginase (EC 3·5·3·1) activity threefold. Fasting for 30 h decreased this activity by 50%.2. Liver xanthine dehydrogenase was slightly increased after force-feeding and decreased following fasting.3. The specific activities of two pentose-phosphate-cycle enzymes were not significantly affected by force-feeding, but glucose-6-phosphate dehydrogenase (EC 1.1.1.49) decreased following fasting.4. The over-all secretion of digestive enzymes increased parallel to the increase in food consumption. Therefore, despite an increased absolute weight of the pancreas and intestinal chyme, specific activities were the same in the force-fed and ad lib.-fed groups, except for a higher activity in intestinal amylase.5. Fasting did not affect the pancreatic enzymic activities.

PROGESTERONE AND INSULIN-RESISTANCE: STUDIES OF PROGESTERONE ACTION ON GLUCOSE TRANSPORT, LIPOGENESIS AND LIPOLYSIS IN ISOLATED FAT CELLS OF THE FEMALE RAT

1981 ◽  
Vol 88 (3) ◽  
pp. 455-462 ◽  
Author(s):  
M.-TH. SUTTER-DUB ◽  
B. DAZEY ◽  
E. HAMDAN ◽  
M.-TH. VERGNAUD
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate ◽  
Fat Cells ◽  
Female Rat ◽  
Fat Cell ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Glucose Phosphorylation ◽  
Rate Limiting

The effects of progesterone on isolated rat adipocytes were studied in vitro during various steps of glucose metabolism, transport, lipogenesis and lipolysis. Progesterone decreased the phosphorylation of glucose into glucose-6-phosphate as assessed by measuring the uptake of 2-deoxyglucose but it had no effect on transmembrane transport of glucose as determined by measuring the entry of 3-0-methylglucose into the cell. As glucose phosphorylation is a rate-limiting step of the pentose-phosphate pathway, these data could explain the inhibition of lipogenesis and the enhancement of lipolysis observed when progesterone is present in incubation medium. Progesterone might thus modulate a regulatory step of glucose metabolism and antagonize insulin action in the fat cell.

scholarly journals Underestimation of the Pentose–Phosphate Pathway in Intact Primary Neurons as Revealed by Metabolic Flux Analysis

2013 ◽  
Vol 33 (12) ◽  
pp. 1843-1845 ◽  
Author(s):  
Patricia Rodriguez-Rodriguez ◽  
Emilio Fernandez ◽  
Juan P Bolaños
Keyword(s):  
Pentose Phosphate Pathway ◽  
Metabolic Flux ◽  
Pentose Phosphate ◽  
Flux Analysis ◽  
Primary Neurons ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Total Glucose ◽  
Rate Limiting ◽  
Glycolytic Rate

The rates of glucose oxidized at glycolysis and pentose–phosphate pathway (PPP) in neurons are controversial. Using [3-3H]-, [1-14C]-, and [6-14C]glucose to estimate fluxes through these pathways in resting, intact rat cortical primary neurons, we found that the rate of glucose oxidized through PPP was, apparently, ∼14% of total glucose metabolized. However, inhibition of PPP rate-limiting step, glucose-6-phosphate (G6P) dehydrogenase, increased approximately twofold the glycolytic rate; and, knockdown of phosphoglucose isomerase increased ∼1.8-fold the PPP rate. Thus, in neurons, a considerable fraction of fructose-6-phosphate returning from the PPP contributes to the G6P pool that re-enters PPP, largely underestimating its flux.

scholarly journals The metabolism of S-nitrosothiols in the trypanosomatids: the role of ovothiol A and trypanothione

2003 ◽  
Vol 371 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Ryan N. VOGT ◽  
Daniel J. STEENKAMP
Keyword(s):  
Reductase Activity ◽  
Order Rate Constant ◽  
Second Order ◽  
Formaldehyde Dehydrogenase ◽  
Thiyl Radicals ◽  
Order Rate ◽  
Rate Limiting Step ◽  
Low Levels ◽  
Rate Limiting

It has recently been established that nitrosoglutathione is the preferred substrate of the glutathione-dependent formaldehyde dehydrogenase from divergent organisms. Trypanosomatids produce not only glutathione, but also glutathionylspermidine, trypanothione and ovothiol A. The formaldehyde dehydrogenase activity of Crithidia fasciculata was independent of these thiols and extracts possessed very low levels of nitrosothiol reductase activity with glutathione or its spermidine conjugates as the thiol component. Although ovothiol A did not form a stable nitrosothiol, it decomposed the S-nitroso groups of nitrosoglutathione (GSNO) and dinitrotrypanothione [T(SNO)2] with second-order rate constants of 19.12M-1·s-1 and 8.67M-1·s-1 respectively. The reaction of T(SNO)2 with ovothiol A, however, accelerated to a rate similar to that seen with GSNO. Ovothiol A can act catalytically to decompose these nitrosothiols, although non-productive mechanisms exist. The catalytic phase of the reaction was dependent on the production of thiyl radicals, since it was abolished in the presence of 5,5-dimethyl-1-pyrroline-N-oxide and the formation of nitric oxide could be detected by means of the conversion of oxyhaemoglobin into methaemoglobin. The rate-limiting step in the catalytic process was the reduction of oxidized ovothiol species and, in this respect, T(SNO)2 is a more efficient substrate than GSNO. Trypanothione decomposed GSNO with a second-order rate constant of 0.786M-1·s-1 and the major nitrogenous end product changed from nitrite to ammonia as the ratio of thiol to nitrosothiol increased. The results indicate that ovothiol A acts in synergy with trypanothione in the decomposition of T(SNO)2.

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