Contribution Of Pentose Cycle Research Articles

Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans.

The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway.

Testing of the assumptions made in estimating the extent of futile cycling.

In estimating glucose and fructose 6-phosphate futile cycling in vivo, complete detritiation of [2-3H]glucose is assumed at the glucose 6-phosphate level, [3-3H]glucose at triose phosphate formation, and [6-3H]glucose in its conversion to glucose via pyruvate. [3-3H]glucose detritiation via the pentose cycle is assumed to be negligible. Normal and non-insulin-dependent diabetic subjects, in the basal state and infused with glucose, were given [2-3H,2-14C]galactose, and 3H-to-14C ratios in blood glucose were determined. [2-3H,2-14C]glucose was given with acetaminophen, and 3H/14C in urinary glucuronide was determined. Detritiation at glucose 6-phosphate was approximately 80%. [3-3H,1-14C]fructose was infused, and 3H/14C was determined in blood glucose and urinary glucuronide. At triose phosphate, 75-90% of the 3H was removed. The pentose cycle contribution was only a few percent. [6-3H,6-14C]glucose was infused, and 3H/14C in blood lactate was determined. [3-3H,3-14C]lactate was infused, and ratios in blood glucose were determined. Maximally, 10% of 3H from [6-3H]glucose was retained. If glucose and galactose are metabolized in the same hepatic site(s), glucose conversion to three-carbon intermediates in the indirect pathway of glycogen formation occurs in extrahepatic tissue(s). Reported estimates of futile cycling, although qualitatively correct, quantitatively require correction.

Deltamethrin: In vivo effects on glucose catabolism in Locusta migratoria L

The in vivo effects of deltamethrin (a pyrethroīd insecticide) on pathways of glucose catabolism have been investigated in 20-day-old male adult Locusta migratoria. The relative contributions of the pentose cycle and the glycolytic-citric cycle were evaluated by a radiorespirometric method using d-[1- 14C]glucose and d-[6- 14C]glucose as substrates. The injection of nonlethal and LD 50 doses of ethanolic solutions of deltamethrin significantly modified the in vivo glucose degradation. A dose-dependent stimulation of the respiratory rate was observed. The C 6 C 1 ratio and the conversion of d-[6- 14C]glucose into 14CO 2 were increased in both cases. In contrast, the conversion of d-[1- 14D]glucose into 14CO 2 was reduced, especially at the LD 50 dose. Deltamethrin reduced the contribution of pentose cycle and diverted substrates toward the glycolytic pathway followed by the Krebs cycle.

Major metabolic pathways of glucose in normal human lymphocytes and the effect of cortisol

1. 1. Intact normal human lymphocytes were incubated in vitro with [1- 14C]-, [2- 14C]- and [6- 14C]glucose and the fate of 14C in the cells was followed. Parallel incubations with the addition of cortisol were performed. 2. 2. Glucose was catabolized mainly via the Embden-Meyerhof pathway and approx. 70% of utilized glucose was converted to lactate. The contribution of the pentose cycle to overall glucose metabolism was approx. 2% and recycling in the pentose cycle was demonstrated. Approx. 1% of utilized glucose was metabolized via the Krebs cycle. Of the utilized glucose label 2–4% was accounted for by glycogen- 14C and approx. 2% by 14C in supporting tissue. 14C incorporation into acetate was low and 14C activity in total lipids was extremely low. 3. 3. Degradations of glucose liberated from glycogen indicated an extensive operation of the transaldolase exchange mechanism and absence or very low activity of fructose 1,6-diphosphatase. The labeling pattern in the C-1, C-2 and C-3 positions of glucose obtained from glycogen, when the cells were incubated with [1- 14C]- and [2- 14C]glucose, suggested reversal of the pentose pathway. Observed discrepancies between randomization in lactate and glucose of glycogen could possibly be explained by assuming the existence of 2 separate glucose 6-phosphate pools. 4. 4. Cortisol inhibited glucose utilization. The relative contribution of glycogen synthesis, lactate formation, pentose cycle and Krebs cycle to overall glucose metabolism was unchanged by cortisol. Concomitantly total lactate production was no suppressed in the presence of cortisol, suggesting lactate formation from endogenous sources.

Estimation of the pentose cycle contribution to glucose metabolism in tissue in vivo.

Estimation of the pentose cycle contribution to glucose metabolism in tissue in vivo.

The Pentose Cycle, Triose Phosphate Isomerization, and Lipogenesis in Rat Adipose Tissue

1. The relationship between the specific activities of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate from glucose-1-14C and -6-14C and triose-P isomerization has been analyzed. The specific activities are a function of three independent variables, the rate of triose-P isomerization, the contribution of the pentose cycle to glucose metabolism, and relative outflow from the dihydroxyacetone-P or glyceraldehyde-P pools. Equations to calculate the relative specific activities of these two compounds, the rate of triose-P isomerase, and the pentose cycle contribution under conditions of incomplete isotopic equilibration of triose-P have been derived. When synthesis of glycerol is limited, previously derived methods for evaluating the pentose cycle with the use of glucose-1-14C and -6-14C can be applied. 2. The contribution of the pentose cycle was calculated from 14C yields from glucose-1-14C and -6-14C, and from uniformly labeled 14C-glucose, and from degradation of glycerol derived from glucose-2-14C on incubation of epididymal fat tissue from rats. On the addition of epinephrine and growth hormone, similar estimates were obtained by three independent methods, theoretically valid in the absence of complete triose-P isomerization. Two methods, requiring complete equilibration, differed. Under other conditions, all five methods agreed closely. The contribution of the pentose cycle was correlated with fatty acid synthesis. In tissue from rats fasted and refed, or with insulin stimulation, the contribution averaged 25%. In the presence of growth hormone it averaged 11%. In rats fed ad libitum and without hormone, the contribution averaged 14%, and 7% in the presence of epinephrine. 3. Specific activities of the triose phosphates from glucose-1-14C and -6-14C and their rates of isomerization were estimated for the intact adipose tissue. The relative rates ranged from 2 to 10 times those of glucose utilization and were not greatly affected by dietary conditions or hormones. 4. Glucose utilization by tissue from rats fasted and refed, with insulin present, was seven times as high as that of tissue from rats fed ad libitum and without insulin. Of the utilized glucose carbon, 38% appeared in CO2, 45% in fatty acids, and 5% in glycerol. About two-thirds of the CO2 was derived via pyruvate decarboxylation and one-third via the pentose cycle; very little CO2 was evolved via the Krebs cycle. Epinephrine stimulated glucose utilization 3-fold. Of the glucose carbon, 30% appeared in CO2, 7% in fatty acids, and 40% in glycerol. Over half of the CO2 arose via the Krebs cycle, and one-tenth or less via the pentose cycle. Depending on diet and hormones, intermediate patterns between these two extremes were observed. 5. A balance of formation and utilization of reduced pyridine nucleotides in the cytoplasm was established. The total amount of reduced di- and triphosphopyridine-nucleotides formed in the cytoplasm was in small excess over hydrogen equivalents required for the synthesis of fatty acids, glycerol, and lactate. Under conditions of enhanced fatty acid synthesis, the TPNH formed via the pentose cycle was found to provide only 59 to 88% of the hydrogen required for fatty acid synthesis.

Estimation of the Glucuronic Acid Pathway Contribution to Glucose Metabolism in Adipose Tissue and the Effect of Growth Hormone

A definite contribution of the glucuronic acid pathway to total glucose metabolism by rat adipose tissue in vitro in the presence of growth hormone preparations has not been found. Randomization of 14C of glucose-5-14C into glycerol and glucose-1-14C and -2-14C into glycogen on incubation of rat epididymal tissue indicates that the pathway contributes at most only a few per cent to the over-all metabolism of glucose. Results of incubations with glucose-1-14C and -6-14 are in accord with metabolism solely via the pentose cycle, Embden-Meyerhof pathway, and Krebs cycle. Thus, essentially all of the 14C utilized on incubation of glucose-1-14C and -6-14C is isolated in products formed via these pathways. Nonequilibration of dihydroxyacetone phosphate with glyceraldehyde 3-phosphate occurs, and this results in a preferential oxidation to CO2 of carbon 6 as compared to carbon 1 via the Krebs cycle. This coupled with an increase in the fraction of carbon 3 of pyruvate converted to CO2 and a decreased pentose cycle contribution in the presence compared to the absence of the preparations can account for the enhanced yields of 14CO2 from glucose-6-14C as compared to -1-14C that have been reported on growth hormone addition.

Contribution of the pentose cycle to glucose metabolism in muscle

Glucose-2-C 14 has been incubated with abdominal muscle, diaphragm, and slices of heart from baby and adult mice. Glucose from glycogen and ribose from nucleotides have been degraded. From the C 14-distribution in the glucose, the pentose cycle contribution to over-all glucose metabolism in abdominal muscle and diaphragm could not definitely be established, but it does not exceed 2%; in heart it appears to be somewhat higher. Distributions of C 14 in glucose from glycogen and ribose are in accord with incorporation of C 14 via the oxidative and nonoxidative portions of the cycle. While incorporation via the oxidative portion can be attributed to synthesis, incorporation via the nonoxidative portion may occur via exchange reactions rather than synthesis.