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PubMed1990

Choice and use of tracers.

The isotope dilution method has been widely employed to measure glucose turnover in man. The validity of this technique depends upon several assumptions. First, it is assumed that the selected model of glucose kinetics is valid. Under nonsteady state conditions this has recently been challenged for the most commonly used single compartment model. Secondly, it is assumed that the isotope is metabolized in the same manner as unlabeled glucose. If the isotope loses its label when subject to a substrate cycle (for example, [2-3H]glucose in glucose to glucose 6-phosphate cycling), an overestimate of glucose disposal will result. In contrast, if isotope that has been cleared (for example [6-3H]glucose in hepatic glucogen) is recycled into the systemic circulation, an underestimation of glucose turnover will result. Thirdly, it is assumed that measurement of specific activity is accurate. It has recently been shown that many commercially available tritiated (but not 14C) isotopes contain radioactive nonglucose contaminants which have a slower clearance rate than glucose under conditions of high glucose turnover. This can result in overestimates of specific activity and underestimates of glucose appearance, leading to calculated negative hepatic glucose release. While this problem may be avoided with purified tritiated glucose tracers, a similar problem with stable isotopes of glucose remains to be determined. In summary, the choice of glucose isotope should reflect the probability of substrate cycling and isotope cycling in the experiment in question. Care should be taken to ensure purified isotopes are selected and that the model of glucose kinetics used is valid during the conditions to be studied.

Animals↗
PubMed1994

Metabolic responses to substrate futile cycling in Escherichia coli.

A cyclic pathway between phosphoenolpyruvate and oxaloacetate was created in Escherichia coli by simultaneous overexpression of phosphoenolpyruvate carboxykinase (encoded by pck) and phosphoenopyruvate carboxylase (encoded by ppc) from a multicopy plasmid under the control of the tac promoter. The simultaneous overexpression of these two enzymes stimulated oxygen and glucose consumption, reduced growth yields, and resulted in high level excretion of pyruvate and acetate. These responses were abolished when either pck or ppc was deleted from the plasmid or when both enzymes were inactivated by mutation. Therefore, the observed effects imply the existence of futile cycling. Incremental induction of futile cycling showed that stimulation of oxygen consumption was the first response, followed by the increased glucose consumption and the excretion of fermentation products. The specific growth rate of E. coli was insensitive to futile cycling per se, because the growth rate was also reduced by the overexpression of inactive enzymes at high levels, and the activity of the two enzymes did not inhibit growth further. Wild-type cells appear to be capable of compensating for the increased ATP drain due to futile cycling but cannot be as effective when a tricarboxylic acid cycle enzyme, alpha-ketoglutarate dehydrogenase, is defective.

Escherichia coli↗
PubMed2002

Carbohydrate cycling in micro-organisms: what can (13)C-NMR tell us?

The extension of (13)C-nuclear magnetic resonance (NMR) techniques to study cellular metabolism over recent years has provided valuable data supporting the occurrence, diversity and extent of carbon cycling in the carbohydrate metabolism of micro-organisms. The occurrence of such cycles, resulting from the simultaneous operation of different and sometimes opposite individual steps, is inherently related to the network organisation of cellular metabolism. These cycles are tentatively classified here as 'reversibility', 'metabolic' and 'substrate' cycles on the basis of their balance in carbon and cofactors. Current hypotheses concerning the physiological relevance of carbohydrate cycles are discussed in light of the (13)C-NMR data. They most likely represent system-level mechanisms for coherent and timely partitioning of carbon resources to fit with the various biosynthetic, energetic or redox needs of cells and/or additional strategies in the adaptive capacity of micro-organisms to face variation in environmental conditions.

Azotobacter vinelandii↗
PubMed2003

Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test.

Increased glucose cycling between glucose and glucose-6-phosphate is characteristic of insulin resistance and hyperglycemia seen with Type II diabetes. Traditionally, glucose cycling is determined by the difference between hepatic glucose output measured with separate [2-3H]glucose and [6-3H]glucose infusions. We demonstrate a novel method for determining hepatic glucose recycling from an intraperitoneal glucose tolerance test (IPGTT). A single tracer, [1, 2-13C(2)]glucose (a M2 glucose isotopomer), was administered at 1mg/g body weight to 4-month-old C57BL/6 mice. Hepatic glucose recycling was monitored by the appearance of a plasma M1 isotopomer of glucose, which is produced by the action of the pentose cycle on the M2 glucose isotopomer in the liver. The initial M2 enrichment was 56% and decreased to 13% at the end of 3 h, and the M1 enrichment peaked at 2 h. The ratio of plasma M1/M2 glucose increased linearly with time to approximately 25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant k(HR). k(HR) estimates glucose/glucose-6-phosphate futile cycling, along with glucose recycling through the pentose cycle. These observations demonstrate complex substrate cycling during an IPGTT using a single stable isotope tracer.

Animals↗
PubMed2003

Modulating carbonyl cytotoxicity in intact rat hepatocytes by inhibiting carbonyl metabolizing enzymes. II. Aromatic aldehydes.

The molecular cytotoxic mechanisms of dietary benzaldehydes towards hepatocytes and its modulation by metabolizing enzymes were compared. Salicylaldehyde was found to be the most cytotoxic followed by cinnamaldehyde and both rapidly depleted some glutathione before an inhibition of respiration occurred, which preceded cell lysis. Reactive oxygen species were formed, but lipid peroxidation was induced with cinnamaldehyde, but not salicylaldehyde. Glutathione depleted hepatocytes were more susceptible to cytotoxicity. Mitochondrial toxicity and cytotoxicity were prevented by glycolytic substrates (e.g. fructose), citric acid cycle substrates (e.g. glutamine) or cyclosporin, the mitochondrial permeability transition inhibitor. Inhibition of mitochondrial ALDH with chloral hydrate, crotonaldehyde or citral or decreasing mitochondrial NAD+ with rotenone increased cinnamaldehyde induced cytotoxicity with a much smaller effect on salicylaldehyde induced cytotoxicity. Cyanamide was the most effective ALDH inhibitor for increasing cinnamaldehyde induced cytotoxicity, presumably because cyanamide also inhibits microsomal ALDH. Although cinnamaldehyde was a better substrate than salicylaldehyde for ADH1, cytosolic NADH generators (e.g. xylitol) prevented salicylaldehyde and cinnamaldehyde cytotoxicity similarly. This could be explained as salicylaldehyde was not a substrate for the ALDHs and would then be more dependent on ADH for detoxification.

Aldehyde Dehydrogenase↗
PubMed1993

The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.

Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.

Absorption↗
PubMed1988

Biochemical markers of aging.

It is the purpose of this report to identify possible metabolic deficiencies that might serve as biochemical markers of aging. It is proposed that the multiplicity of physical and physiological changes associated with aging could be most readily explained by alterations in the regulation and/or the activities of enzymes that occupy central positions in metabolism. Specifically, a search for metabolic markers of aging might include efforts to determine if there are age-related changes in the following enzymes or enzyme systems: (a) allosteric enzymes that catalyze reactions in highly branched metabolic pathways; (b) enzymes that catalyze opposing reactions between metabolites that are common intermediates in biosynthetic and biodegradative pathways (reactions which in the absence of final control would lead to futile substrate cycling); (c) enzymes that catalyze bimolecular reactions in which one member of a coenzyme pair is a cosubstrate (e.g., reactions involving NAD+ or NADH); (d) enzymes that are regulated by phosphorylation/dephosphorylation cycles; and (e) G-protein-dependent enzyme systems. It is also emphasized that changes in the concentrations and ratios of coenzyme substrate pairs (e.g., [NAD]/[NADH], [CoA]/[acyl CoA]) and the energy charge ratio [ATP] + 0.5 [ADP]/[ATP] + [ADP] + [AMP] may signal deviations from normal metabolism and therefore might be reliable markers of aging. In addition, because of their critical roles in metabolism, changes in the concentration of GTP, GDP and the second messengers, c-AMP, c-GMP should be monitored. Finally, it is noted that the accumulation of the altered forms of some enzymes which occurs during aging reflects imbalance between posttranslational modification of the enzymes and the degradation of the altered enzyme forms. The biological mechanisms involved and the genetic implications are discussed.

Aging↗
PubMedDate not supplied

Nucleosides and glutamine are primary energy substrates for embryonic and adult chicken red cells.

It has been assumed that glucose is a major energy yielding substrate for chicken red blood cells. In this report we show that glucose fails to maintain cellular ATP levels in embryonic and mature chicken erythrocytes during overnight incubation. Of over a dozen metabolites tested, inosine, guanosine, and glutamine were the most efficacious ATP-sustaining substrates. Of seven potential citric acid cycle substrates, only glutamine significantly sustained ATP levels. Incubation with inosine plus glutamine sustained the ATP level at over 70% of the initial value found in embryonic chicken red cells. Uridine, cytidine, xanthosine, glutamate, and pyruvate were ineffective substrates. Similar results were obtained with adult erythrocytes, except that glutamine plus inosine fully sustained ATP levels during long-term incubation. Adenosine did not sustain ATP levels. Below 1 mM, the adenosine level was rapidly exhausted and above 1 mM its presence led to cell lysis. The ability of some nucleosides to maintain ATP levels is consistent with the high numbers of nitrobenzylthioinosine binding sites (nucleoside transporter sites) both in mature chicken red cells (approximately 10,000 sites/cell) and in embryonic red cells (approximately 30,000 sites/cell). Unlike pig red cells which switch from glucose to nucleosides at the erythrocyte stage, chicken cells show primary dependence on nucleoside metabolism at the embryonic stage.

Adenosine↗
PubMed1992

Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis.

Understanding the regulation of hepatic glucose metabolism had its foundation in the elucidation of several pathways, but recent advances have come from the application of molecular genetics. Five years ago little was known about the primary structure of the key regulatory enzymes. Since then, the primary sequence of liver GK, 6-PF-1-K, Fru-1,6-P2ase, PK, PEPCK, and 6-PF-2-K/Fru-2,6-P2ase have been derived from cDNA sequences and/or determined by direct protein sequencing. This has provided new insights into the molecular mechanisms of catalysis and the regulation of these enzymes by covalent modification. Isolation of the cDNAs for these enzymes also has allowed for the quantitation of specific mRNAs and permitted analysis of hormonal control of specific gene expression. The genes for these enzymes have been isolated and sequenced, and their promoter regions are being identified and characterized. Hormone response elements have been delineated in several of the promoters. The promoter regions for 6-PF-2-K/Fru-2,6-P2ase and Fru-1,6-P2ase have also been identified, and future research will focus on the elucidation of the mechanisms whereby hormones regulate the expression of these genes. A number of generalizations can be made about the regulation of gene expression of glycolytic/gluconeogenic enzymes. First, there is coordinate hormonal regulation of gene expression and these effects are consonant with their physiologic actions. Insulin induces the mRNAs that encode glycolytic enzymes and represses the mRNAs that encode gluconeogenic enzymes; cAMP has opposite effects. Both can increase or decrease transcription. Whereas insulin and cAMP affect all of these mRNAs, glucocorticoids appear to have a more restricted action. Second, transcriptional and posttranscriptional regulatory mechanisms are involved. The synthesis of all of the mRNAs discussed is regulated by hormones. Relatively little is known about how mRNA stability is regulated in general, but it is clear that PEPCK mRNA is stabilized by agents that increase the rate of transcription of the gene. Under appropriate metabolic signals this dual control of mRNA synthesis and stability provides for a long-term increase in PEPCK mRNA and protein. Studies with PK mRNA are less direct, but suggest a similar dual mechanism. It will be interesting to see whether multilevel regulation is restricted to these two mRNAs, both of which are involved in the same substrate cycle, or whether the stability of other mRNAs involved in hepatic glucose metabolism is also affected. Third, glucose appears to be important in the regulation of these hepatic genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons.

When embryonic central nervous system neurons are seeded at low densities with Eagle's basal medium supplemented with the serum substitute N1, glucose, and glutamine, neuronal survival for even 24 h requires the additional supply of exogenous pyruvate--and so does the survival of many peripheral nervous system neurons. Pyruvate can be replaced by alpha-ketoglutarate or oxaloacetate, but not by Krebs cycle substrates that are not keto acids. Most other alpha-keto acids tested (though not beta- or gamma-keto acids) also mimic pyruvate. The apparent equivalence to pyruvate of all these compounds includes identical ED50 values (300 microM for embryonic avian fore-brain neurons, 30-40 microM for rat hippocampal neurons), and also identical susceptibilities to the pyruvate-sparing effects of other low-molecular-weight agents present in Dulbecco's modified Eagle's medium or in astroglia conditioned medium. The substitute alpha-keto acids, however--unlike pyruvate, alpha-ketoglutarate, or oxaloacetate--support cell survival only in the presence of alpha-amino acids that transaminate to alpha-ketoglutarate, oxaloacetate, or pyruvate. The alpha-keto acids, therefore, operate as acceptors of amino groups from appropriate donors to generate Krebs cycle-relevant substrates. Consistent with this view, [14C]glutamate did not generate appreciable 14CO2 unless accompanied by a suitable alpha-keto acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Hyperammonemia in lysinuric protein intolerance.

Two brothers with hyperdibasicaminoaciduria and postprandial hyperammonemia showed characteristics of lysinuric protein intolerance. Intravenous alanine load produced hyperammonemia that was aborted by oral supplementation with arginine in one brother but not in the other, although both patients had almost the same intestinal malabsorption of arginine. This occurrence suggests that even a small amount of arginine, when absorbed into the blood, can normalize the affected ammonia metabolism of lysinuric protein intolerance. Two patients with cystinuria developed marked hyperammonemia when they received an intravenous alanine load after a 19-hour fast. As both patients displayed a reduced plasma concentration of arginine and ornithine at this time, the hyperammonemia was assumed to arise from the low plasma amino acid level. It seems likely that a decrease in plasma levels of urea cycle substrate causes a failure of the tissue urea cycle metabolism. Thus the impaired ammonia metabolism in lysinuric protein intolerance would be attributed to the low plasma arginine and ornithine levels.

Adolescent↗
PubMed1990

Effects of diet and exercise on the in vivo rates of the triglyceride-fatty acid cycle in adipose tissue and muscle of the rat.

The effects of feeding a low-protein diet (5 percent w/w) and daily exercise on the rates of substrate (futile) cycling between triglyceride and fatty acids (TG-FA cycle) were studied in rats in vivo using a radiochemical assay that involves following the incorporation of tritium from 3H-H2O into the fatty acid and glycerol moieties of triglyceride. Sixty-four rats were fed either a purified control diet (COND) consisting of 70 percent carbohydrate, 20 percent protein, 5 percent fat or an experimental low protein (LPD) diet consisting of 80 percent carbohydrate, 5 percent protein and 10 percent fat (w/w) and were either exercised six days weekly or remained sedentary for six weeks. Both LPD and exercise training (EXT) were found to increase significantly the rate of TG-FA substrate cycling above the rates observed in dietary and sedentary control groups. The LPD increased significantly the rate of cycling in interscapular brown adipose (IBAT), while adipose (WAT) and diaphragm muscle. EXT increased the rates of substrate cycling in soleus, heart, and diaphragm muscle and WAT. Rate of cycling in cardiac or skeletal muscle was one-twentieth that found in adipose tissue. There were also sex differences in the rate of substrate cycling. Substrate cycling in soleus and heart muscle of male animals were consistently higher than respective female treatment groups. Sedentary and EXT LPD animals weighed significantly less than but consumed a similar amount of food to the respective COND animals. These data provide the first in vivo evidence that the rate of substrate cycling can be increased by diet or by exercise training. The possible importance of TG-FA and other substrate cycles on efficiency of energy metabolism and etiology of obesity are discussed.

Adipose Tissue↗
PubMed1976

The effect of hydrogen peroxide on CO2 fixation of isolated intact chloroplasts.

Low concentration of hydrogen peroxide strongly inhibit CO2 fixation of isolated intact chloroplasts (50% inhibition at 10(-5) M hydrogen peroxide). Addition of catalase to a suspension of intact chloroplasts stimulates CO2 fixation 2--6 fold, indicating that this process is partially inhibited by endogenous hydrogen peroxide formed in a Mehler reaction. The rate of CO2 fixation is strongly increased by addition of Calvin cycle intermediates if the catalase activity of the preparation is low. However, at high catalase activity addition of Calvin cycle intermediates remains without effect. Obviously the hydrogen peroxide formed at low catalase activity leads to a loss of Calvin cycle substrates which reduces the rate of CO2 fixation. 3-Phosphoglycerate-dependent O2-evolution is not influenced by hydrogen peroxide at a concentration (5x10(-4) M) which inhibits CO2 fixation almost completely. Therefore the inhibition site of hydrogen peroxide cannot be at the step of 3-phosphoglycerate reduction. Dark CO2 fixation of lysed chloroplasts in a hypotonic medium is not or only slightly inhibited by hydrogen peroxide (2,5x10(-4) M), if ribulose-1,5-diphosphate, ribose 5-phosphate or xylulose 5-phosphate were added as substrates. However, there is a strong inhibition of CO2 fixation by hydrogen peroxide, if fructose 6-phosphate together with triose phosphate are used as substrates. This indicates that hydrogen peroxide interrupts the Calvin cycle at the transketolase step, leading to a reduced supply of the CO2-acceptor ribulose 1,5-diphosphate.

Carbon Dioxide↗
PubMed1990

Nucleotidase activities in soluble and membrane fractions of three different mammalian cell lines.

Soluble cytoplasmic and membrane fractions were prepared from three cultured mammalian cell lines: 3T3 mouse fibroblasts, V79 hamster lung cells, and human "Cherry" B-lymphoblastoid cells. By using relatively specific nucleotidase assays, together with a phosphotransferase assay, the activities of three different enzymes (low-Km nucleotidase, high-Km nucleotidase, and 5'(3')-nucleotidase) capable of dephosphorylating deoxyribonucleoside 5'-monophosphates were determined in these fractions. The three nucleotidases exist simultaneously in all cell lines, but their relative amounts showed large variations. The 5'(3')-nucleotidase dominated Cherry and 3T3 cells, while in V79 cells equal amounts of this enzyme and the high-Km nucleotidase were recovered. In the membrane fractions, the low-Km nucleotidase was the predominant enzyme. We found no evidence for cell-cycle control of any nucleotidase. We postulated earlier that substrate cycles, involving 5'-nucleotidases and deoxyribonucleoside kinases, provide a mechanism for the regulation of deoxyribonucleotide pools. We suggest that both the low-Km nucleotidase and the 5'(3)-nucleotidase are candidate enzymes for such cycles.

Animals↗
PubMed2002

Fermented wheat germ extract inhibits glycolysis/pentose cycle enzymes and induces apoptosis through poly(ADP-ribose) polymerase activation in Jurkat T-cell leukemia tumor cells.

The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC(50) concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G(1) peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased (13)C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC(50) (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.

Apoptosis↗
PubMed1995

Bistability and damped oscillations in the fructose 6-phosphate/fructose 1,6-bisphosphate cycle in cell-free extracts from rat liver.

The dynamics of the fructose 6-phosphate/fructose 1,6-bisphosphate substrate cycle was investigated in cell-free extracts from rat liver. Under conditions of continuous substrate supply different types of stationary states and damped oscillations were observed experimentally and found to be in qualitative agreement with theoretical predictions. Changing the adenylate energy charge of the substrate supply, bistability was shown to be related to irreversible transitions between functionally different branches of stable stationary states.

Animals↗
PubMed1993

Reciprocal effects of proline and glutamine on glycogenesis from glucose and ureagenesis in isolated, perfused rat livers.

L-Proline and L-glutamine were used to probe the inverse relationship between glycogenesis and ureagenesis in isolated, perfused livers from 48-h fasted rats. Both amino acids may provide nitrogen in the form of NH+4 for carbamyl-P synthesis. However, one molecule of glutamine may provide additionally for the synthesis of one molecule of the urea cycle substrate L-aspartate, but proline can provide for the synthesis of a molecule of NH+4 or one molecule of aspartate on an either/or basis only. In all perfusates, glucose was initially 30 mM (to favor phosphotransferase activity of glucose-6-phosphatase) and 0.5 mM 3-mercaptopicolinate was present (to inhibit glyconeogenesis from endogenous substrates, from the added amino acids, and via the indirect pathway). Glycogenesis from glucose, perfusate and hepatic urea formation, and levels of hepatic glucose-6-P, citrulline, PPi, and carbamyl-P were measured. The addition of glutamine to the perfusate markedly stimulated the urea cycle, but not glycogenesis. Hepatic urea level, perfusate urea concentration, and hepatic citrulline and PPi increased while carbamyl-P content decreased. In contrast, proline stimulated glycogenesis from glucose, but not ureagenesis. In the proline-supplemented compared with glutamine group, hepatic glycogenesis and carbamyl-P content increased; hepatic glucose-6-P levels showed a tendency toward increase; and hepatic urea formation, hepatic citrulline, and PPi levels were decreased. These observations are interpreted to support an hepatic mechanism whereby the relative availability of carbamyl-P to the urea cycle and as a substrate for glucose phosphorylation via phosphotransferase activity of the glucose-6-phosphatase system preliminary to glycogenesis from glucose is a major metabolic determinant.

Animals↗