Lactate Precursors Research Articles

Microstructure of Li1+xMn2−xO4 spinels obtained from metal-organic precursors

A metal-organic precursor method was adopted for the preparation of lithium-manganese spinel oxides. EPR spectra of Mn 2+ in solutions and in freeze-dried compositions, as well as IR and DSC of freeze-dried compositions, show that α-hydroxyorganic acids (such as lactic, malic and citric acids) chelate Mn 2+ via hydroxy and carboxylate groups. At 450°C, thermal decomposition of Li-Mn-organic acid precursors with Li/Mn=1.05/1.95 leads to the formation of non-stoichiometric Li[Li y Mn 2–y– Δ □ Δ ]O 4 spinels (0.03<y<0.05; 0.02<δ<0.05). EPR of Mn 4+ was used to throw light on the microstructure of the spinels obtained. For the annealed spinels at 750°C there is a transition from uniform to non-uniform distribution of the excess Mn 4+ ions and the corresponding metal vacancies. As a result, the bulk of the spinel becomes close to the stoichiometric composition Li[Li 0.05 Mn 1.95 ]O 4 , whereas the spinel surface accommodates the excess Mn 4+ ions. The formation of Mn 4+ -rich surface regions depends both on the cooling rate and on the organic acid used in the precursors. Lactate precursors are most appropriate for the preparation of lithium-manganese spinels with a homogeneous cation distribution.

Impairment by interleukin 1 beta and tumour necrosis factor alpha of the glucagon-induced increase in phosphoenolpyruvate carboxykinase gene expression and gluconeogenesis in cultured rat hepatocytes.

The influence of the inflammatory mediators interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) on the glucagon-induced expression of phosphoenolpyruvate carboxykinase (PCK) and on glucose formation via gluconeogenesis was investigated in cultured rat hepatocytes. Gene expression was monitored by determination of mRNA levels and of enzyme activity. Glucose formation was estimated with newly synthesized radioactive glucose derived from a radiolabelled lactate precursor. Glucagon (0.1 or 1 nM) induced PCK mRNA transiently to a maximum 2 h after its application. In the presence of recombinant human (rh) IL1 beta or rhTNF alpha the increase in PCK mRNA levels was totally inhibited at 0.1 nM glucagon, whereas at 1 nM glucagon the maximal increase was inhibited by only 25%. Glucagon (0.1 or 1 nM) induced PCK activity to a maximum after 4 h (4-fold and 6-fold over prestimulatory activity respectively). In the presence of rhIL1 beta or rhTNF alpha the maximal increase was inhibited by approx. 50%. Addition of rhIL1 beta or rhTNF alpha 2 h after glucagon, at the maximal glucagon-induced PCK mRNA levels, accelerated the decay of PCK mRNA. Glucagon (1 or 10 nM) [corrected] increased glucose formation from lactate by 1.3-fold and 1.7-fold respectively over unstimulated rates. In the presence of rhIL1 beta or rhTNF alpha this increase in glucose formation was inhibited by 60-90%. At 0.1 nM, glucagon doubled the intracellular cAMP concentration. This increase was prevented by rhIL1 beta or rhTNF alpha. At 1 nM, glucagon increased cAMP concentrations by 10-fold. In the presence of rhIL1 beta or rhTNF alpha this increase was inhibited by 70%. From the results it is suggested that rhIL1 beta and rhTNF alpha prevented glucagon-stimulated PCK gene expression and gluconeogenesis at least in part by inhibition of the glucagon-stimulated increase in cAMP concentrations.

Effects of selenium on the glycolysis and gluconeogenesis system in rat liver

We studied the effect of selenium on the glycolysis and gluconeogenesis system in the rat liver. Significant decreases in glucose level in the serum were observed from the 4th day after daily intraperitoneal (i.p.) administration of selenite (173 micrograms/kg, 78.9 micrograms/kg of selenium base equivalent). Selenium was also effective in reducing a precursor of gluconeogenesis, lactate, alanine or glycerol, in the serum. Moreover, there were significant decreases in the activities of pyruvate carboxylase and glucose-6-phosphatase, a rate-limiting enzyme of gluconeogenesis, in the liver of selenium-treated rates. On the contrary, the activities of glycokinase and phosphofructokinase, a rate-limiting enzyme of glycolysis, in the liver of rat treated with selenium significantly increased in comparison with the control group. These data, therefore, indicated that the hypoglycemic effect of selenium might be due to the acceleration of glucose metabolism and the inhibition of glucose synthesis in the liver, suggesting a decrease in a source of precursor supply for the gluconeogenesis.

Lactate Genesis by Rat Liver and Muscle during Development

Lactate has been shown to be an important fuel for brain metabolism during early postnatal development (1). In an attempt to identify the source(s) of lactate in the postnatal rat, we have studied the in vitro catabolism of glucose, galactose, fructose, alanine, glycerol, and octanoate in liver and muscle minces prepared from suckling rat pups. Whereas galactose, fructose, and octanoate were found to be lactagenic (lactate generating) in liver, glucose was the sole lactate precursor in muscle. Galactose was most effective as a hepatic lactate source at 3 d of age. Thereafter, the production of lactate from galactose decreased to reach control levels by 15 d of age. In contrast, fructose or octanoate were lactagenic throughout development. Lactate formation from galactose was completely halted by iodoacetate, inhibited by high galactose concentrations, and suppressed by fasting. The absence of oxygen increased lactate production from either fructose or octanoate, but it did not affect lactagenesis from galactose. Muscle minces produced lactate from glucose in an age-dependent manner similar to the development pattern of lactate formation from galactose by liver. Because lactose-derived galactose is readily available during suckling, it is suggested that galactose-based hepatic lactagenesis serves a unique role in maintaining the supply of lactate during early postnatal development. This hepatic capability may augment glucose-based muscle lactate synthesis at a time when lactate is a major brain fuel.

Hexose monophosphate shunt measurement in cultured cells with [1- 13C]glucose: Correction for endogenous carbon sources using [6- 13C]glucose

Hexose monophosphate shunt (HMPS) activity can be measured with 1H nuclear magnetic resonance spectroscopy or gas chromatography-mass spectrometry by monitoring the differential production of [3- 13C]lactate and [3- 12C]lactate from the degradation of [1- 13C]glucose. Errors in measurement of HMPS activity can arise from unlabeled lactate precursors, by recycling of HMPS products, and by incomplete fractional enrichment of labeled glucose. A method utilizing cultured cells incubated with [1- 13C]glucose in parallel with incubations using [6- 13C]glucose to correct for all these problems is presented. In cultured rat C6 glioma and 9L gliosarcoma cells, failure to apply this correction results in an approximately twofold overestimation of HMPS activity.

Fermentations by saccharolytic intestinal bacteria

Most nonsporing anaerobes of the intestinal tract use the Embden-Meyerhof-Parnas scheme to ferment carbohydrates. Almost all of them oxidize pyruvate, the key fermentation intermediate, to acetyl coenzyme A and CO2 with reduction of a low-potential electron acceptor. H2 is formed from the low potential acceptor or from NADH. Pyruvate is a precursor of lactate, and phosphoenolpyruvate is a precursor of succinate and propionate. Ethanol, acetate, and butyrate are formed from acetyl coenzyme A. Formate is produced by reduction of CO2 by Ruminococcus albus. Heme is required by human Bacteroides for the formation of succinate and, in the presence of vitamin B12, propionate. A fermentation equation derived from the concentration of volatile acids found in human feces suggests that the fermentation in the large intestine is similar to the rumen fermentation.