The pentose phosphate pathway in rabbit liver. Studies on the metabolic sequence and quantitative role of the pentose phosphate cycle by using a system <i>in situ</i>

Williams, John F.; Rienits, K.G.; Schofield, Philip J.; Clark, Michael G.

doi:10.1042/bj1230923

Cited by 51 publications

(33 citation statements)

References 45 publications

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“…NADPH and inorganic phosphate are both inhibitors of these enzymes (Glasser and Brown 1955), but the concentration of each of these metabolites decreased in the liver as the level of administered glucose was increased. Fructose 1,6-diphosphate is also an inhibitor of 6-phosphogluconate dehydrogenase (Dyson and D'Orazio 1971), but the twofold increase in the concentration of this metabolite would not be expected to bring about a sixfold decrease in the C-l : C-6 ratio, particularly when C-l : C-6 ratios of 3 have been obtained in rabbit liver where the concentration of fructose 1,6-diphosphate was far greater than those reported here (Williams et al 1971b).…”

Section: Discussioncontrasting

confidence: 68%

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

Jd¹,

Irving²,

Pf³

et al. 1974

Aust. Jnl. Of Bio. Sci.

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Increasing the blood glucose levels from 88 to 400 mg/IOO ml in rabbit liver in situ during 5-min time intervals resulted in a decrease in the production of C02 from C-I of liver glucose together with a slight increase in the oxidation of C-6 of glucose; this was caused by a high glucose-induced decrease in the activity of the oxidative pentose phosphate pathway. Increasing the glucose concentrations also resulted in a threefold increase in the levels of palmitoyl-and stearoyl-CoA esters at a glucose load of 0·8 g; this is consistent with a specific feed-back inhibition of the production of NADPH by reactions of the oxidative pentose phosphate pathway by long-chain fatty acyl-CoAs. A decrease in plasma free fatty acids occurred when blood glucose levels were raised; this was associated with an increase in the concentration of free fatty acids in liver.There was a decreased glucose output by liver following an increased glucose load. In liver there were increases in AMP levels, decreased ATP levels, a twofold increase in fructose 1,6-diphosphate and a fall in glucose 6-phosphate and fructose 6-phosphate concentrations. These changes are indicative of the decreased gluconeogenic flux caused through inhibition of hexosediphosphatase by AMP, and the elevated levels of the long-chain fatty acyl-CoA esters probably acted to inhibit adenine nucleotide translocation across the mitochondrial membrane. The formation of sn-glycero-3-phosphate appears to be the rate-limiting step for relieving the inhibitions caused by the accumulation of long-chain fatty acyl-CoAs.

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Section: Discussioncontrasting

confidence: 68%

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

Jd¹,

Irving²,

Pf³

et al. 1974

Aust. Jnl. Of Bio. Sci.

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“…The percentage distribution of 14 C isotope in the individual carbons of glucose was determined as 14 CO 2 using a combination of microbiological and chemical methods (Williams et al. 1971). …”

Section: Methodsmentioning

confidence: 99%

The metabolic significance of octulose phosphates in the photosynthetic carbon reduction cycle in spinach

Williams

MacLeod

2006

Photosynth Res

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Abstract14 C-Labelled octulose phosphates were formed during photosynthetic 14 CO 2 fixation and were measured in spinach leaves and chloroplasts. Because mono-and bisphosphates of D-glycero-D-idooctulose are the active 8-carbon ketosugar intermediates of the L-type pentose pathway, it was proposed that they may also be reactants in a modified CalvinBenson-Bassham pathway reaction scheme. This investigation therefore initially focussed only on the ido-epimer of the octulose phosphates even though 14 C-labelled D-glycero-D-altro-octulose mono-and bisphosphates were also identified in chloroplasts and leaves.14 CO 2 predominantly labelled positions 5 and 6 of D-glycero-D-ido-octulose 1,8-P 2 consistent with labelling predictions of the modified scheme. The kinetics of 14 CO 2 incorporation into ido-octulose was similar to its incorporation into some traditional intermediates of the path of carbon, while subsequent exposure to 12 CO 2 rapidly displaced the 14 C isotope label from octulose with the same kinetics of label loss as some of the confirmed Calvin pathway intermediates. This is consistent with octulose phosphates having the role of cyclic intermediates rather than synthesized storage products. (Storage products don't rapidly exchange isotopically labelled carbons with unlabelled CO 2 .)A spinach chloroplast extract, designated stromal enzyme preparation (SEP), catalysed and was used to measure rates of CO 2 assimilation with Calvin cycle intermediates and octulose and arabinose phosphates. Only pentose (but not arabinose) phosphates and sedoheptulose 7-phosphate supported CO 2 fixation at rates in excess of 120 lmol h -1 mg -1 Chl. Rates for octulose, sedoheptulose and fructose bisphosphates, octulose, hexose and triose monophosphates were all notably less than the above rate and arabinose 5-phosphate was inactive. Altro-octulose phosphates were more active than phosphate esters of the ido-epimer. The modified scheme proposed a specific phosphotransferase and SEP unequivocally catalysed reversible phosphate transfer between sedoheptulose bisphosphate and D-glycero-Dido-octulose 8-phosphate. It was also initially hypothesized that arabinose 5-phosphate, an L-Type pentose pathway reactant, may have a role in a modified Calvin pathway. Arabinose 5-phosphate is present in spinach chloroplasts and leaves. Radiochromatography showed that 14 C-arabinose 5-phosphate with SEP, but only in the presence of an excess of unlabelled ribose 5-phosphate, lightly labelled ribulose 5-phosphate and more heavily labelled hexose and sedoheptulose mono-and bisphosphates. However, failure to demonstrate any CO 2 fixation by arabinose 5-phosphate as sole substrate suggested that the above labelling may have no metabolic significance. Despite this arabinose and ribose 5-phosphates are shown to exhibit active roles as enzyme co-factors in transaldolase and aldolase exchange reactions that catalyse the epimeric interconversions of the phosphate esters of ido-and altro-octulose. Arabinose 5-phosphate is presented as playing this role...

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“…14,15,17,26,27 δ-Gluconolactone, which exists in equilibrium with γ-gluconolactone in aqueous media (Scheme 1), enters mammalian cells via glucose transporters and is phosphorylated by gluconokinase (EC 2.7.1.12) to 6-phospho-δgluconolactone, an intermediate in the PPP ox . 28 Based on metabolic data obtained with 14 C labeled glucose and ribose in rabbit liver, 29 flux through the PPP ox appears to be fast enough to allow detection of flux through this pathway within a time frame of 1-2 min. This makes δ-[1-13 C]gluconolactone an attractive tracer for hyperpolarized 13 C studies of the PPP ox , because the 13 C atom in this derivative would be released as 13 CO 2 in the second oxidative step of this pathway.…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarized δ‐[1‐¹³C]gluconolactone as a probe of the pentose phosphate pathway

et al. 2017

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The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis) but simple methods for detecting changes in flux through this pathway are not available. Magnetic resonance imaging of hyperpolarized 13C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-13C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox) in isolated perfused mouse livers. The appearance of hyperpolarized H13CO3− within seconds after exposure of livers to HP-δ-[1-13C]gluconolactone demonstrates that this probe rapidly enters hepatocytes, becomes phosphorylated, and enters the PPPox pathway to produce HP-H13CO3− after three enzyme catalyzed steps (6P-gluconolactonase, 6PGDH, and carbonic anhydrase). Livers perfused with octanoate as their sole energy source show no change in production of H13CO3− after exposure to low levels of H2O2, while livers perfused with glucose and insulin showed a 2-fold increase in H13CO3− after exposure to peroxide. This indicates that flux through the PPPox is stimulated by H2O2 in glucose perfused livers but not in livers perfused with octanoate alone. Subsequent perfusion of livers with non-polarized [1,2-13C]glucose followed by 1H NMR analysis of lactate in the perfusate verified that flux through the PPPox is indeed low in healthy livers and modestly higher in peroxide damaged livers. We conclude that hyperpolarized δ-[1-13C]gluconolactone has the potential to serve as a metabolic imaging probe of this important biological pathway.

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The pentose phosphate pathway in rabbit liver. Studies on the metabolic sequence and quantitative role of the pentose phosphate cycle by using a system in situ

Cited by 51 publications

References 45 publications

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

The metabolic significance of octulose phosphates in the photosynthetic carbon reduction cycle in spinach

Hyperpolarized δ‐[1‐¹³C]gluconolactone as a probe of the pentose phosphate pathway

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The pentose phosphate pathway in rabbit liver. Studies on the metabolic sequence and quantitative role of the pentose phosphate cycle by using a system in situ

Cited by 51 publications

References 45 publications

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

The metabolic significance of octulose phosphates in the photosynthetic carbon reduction cycle in spinach

Hyperpolarized δ‐[1‐13C]gluconolactone as a probe of the pentose phosphate pathway

Contact Info

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Hyperpolarized δ‐[1‐¹³C]gluconolactone as a probe of the pentose phosphate pathway