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PubMed2005

Lactate racemization as a rescue pathway for supplying D-lactate to the cell wall biosynthesis machinery in Lactobacillus plantarum.

Lactobacillus plantarum is a lactic acid bacterium that produces d- and l-lactate using stereospecific NAD-dependent lactate dehydrogenases (LdhD and LdhL, respectively). However, reduction of glycolytic pyruvate by LdhD is not the only pathway for d-lactate production since a mutant defective in this activity still produces both lactate isomers (T. Ferain, J. N. Hobbs, Jr., J. Richardson, N. Bernard, D. Garmyn, P. Hols, N. E. Allen, and J. Delcour, J. Bacteriol. 178:5431-5437, 1996). Production of d-lactate in this species has been shown to be connected to cell wall biosynthesis through its incorporation as the last residue of the muramoyl-pentadepsipeptide peptidoglycan precursor. This particular feature leads to natural resistance to high concentrations of vancomycin. In the present study, we show that L. plantarum possesses two pathways for d-lactate production: the LdhD enzyme and a lactate racemase, whose expression requires l-lactate. We report the cloning of a six-gene operon, which is involved in lactate racemization activity and is positively regulated by l-lactate. Deletion of this operon in an L. plantarum strain that is devoid of LdhD activity leads to the exclusive production of l-lactate. As a consequence, peptidoglycan biosynthesis is affected, and growth of this mutant is d-lactate dependent. We also show that the growth defect can be partially restored by expression of the d-alanyl-d-alanine-forming Ddl ligase from Lactococcus lactis, or by supplementation with various d-2-hydroxy acids but not d-2-amino acids, leading to variable vancomycin resistance levels. This suggests that L. plantarum is unable to efficiently synthesize peptidoglycan precursors ending in d-alanine and that the cell wall biosynthesis machinery in this species is specifically dedicated to the production of peptidoglycan precursors ending in d-lactate. In this context, the lactate racemase could thus provide the bacterium with a rescue pathway for d-lactate production upon inactivation or inhibition of the LdhD enzyme.

Amino Acids↗

PubMed1995

Is lactate-induced myocardial ischaemic injury mediated by decreased pH or increased intracellular lactate?

The detrimental effect of exogenous lactate during ischaemia on post-ischaemic contractile function may be mediated either by a lactate-induced intracellular H+ load or by an increase in intracellular lactate. To distinguish between these two mechanisms, isolated rat hearts were perfused with lactate or pyruvate during low flow ischaemia, the rationale being that both would decrease H+ efflux via lactate/H+ cotransport and lead to decreased pH, but only exogenous lactate would decrease lactate efflux and lead to increased intracellular lactate. 31P NMR spectra were acquired sequentially while hearts were subjected to 32 min low flow (0.5 ml/min) ischaemia and 32 min reperfusion. During ischaemia, hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose (controls) or 11 mM glucose plus either 10 mM lactate or 10 mM pyruvate. Reperfusion of all hearts was with buffer containing only glucose. Intracellular volume, estimated to be 0.52 ml/heart using 31P NMR spectroscopy with phosphonate space markers, did not change under any of the ischaemic conditions during the protocol. Control and pyruvate hearts recovered approximately 85% of pre-ischaemic contractile function, but there was no recovery of function in lactate hearts. This lack of recovery correlated with a 57% loss of ATP during ischaemia, which was significantly greater (P < 0.001) than the 41% loss of ATP in control and pyruvate-perfused hearts. End-ischaemic intracellular pH was 6.60 in both lactate-perfused and control hearts, but significantly lower (P < 0.05) at pH 6.43 in pyruvate-perfused hearts. Both exogenous pyruvate and lactate should have decreased H+ efflux, however the higher pH in the lactate-perfused hearts could be explained by a 60% inhibition of glycolysis, determined by measurement of myocardial lactate production. Thus, the intracellular pH during ischaemia does not necessarily predict the extent of myocardial injury. We propose that lactate-induced damage is a consequence of increased intracellular lactate leading to inhibition of glycolysis, presumably via an increased NADH/NAD ratio. This study highlights the important role of glycolysis in the ischaemic rat heart.

Animals↗

PubMed1997

The effect of dietary energy source during mid to late lactation on liver triglyceride and lactation performance of dairy cows.

Control [1.61 Mcal of net energy for lactation (NEL)/kg of dry matter (DM)], high grain (1.70 Mcal of NEL)/kg of DM), or high fat [1.70 Mcal of NEL/kg of DM with 2.3% tallow (DM basis)] diets were fed to 43 cows (150 +/- 3.1 d in milk) during mid to late lactation to determine effects on performance characteristics, metabolic parameters, or both during mid to late lactation, the dry period, and the first 100 d of the next lactation. All cows received identical diets during the dry period and during early lactation. Increasing the energy density of the diets during mid to late lactation increased DM intake (DMI), plasma nonesterified fatty acid concentration, milk production, and milk protein yield. Compared with the high grain diets, fat supplementation decreased DMI and the percentage of milk protein but increased plasma nonesterified fatty acid concentration without causing elevation of liver triglyceride at the end of mid to late lactation. Increased energy density of the diets did not affect body condition score during mid to late lactation. There were no residual effects for any of the treatments on DMI, lactation performance, or body weight in the subsequent lactation. However, energy supplementation during mid to late lactation increased liver triglyceride content after calving. Compared with high fat diets, high grain diets fed during mid to late lactation increased plasma beta-hydroxy-butyrate concentration in the subsequent lactation. High energy diets fed during mid to late lactation may influence lipid metabolism during the following lactation.

3-Hydroxybutyric Acid↗

PubMed2004

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Acid-Base Equilibrium↗

PubMed2002

Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion.

To test the hypothesis that lactate plays a central role in the distribution of carbohydrate (CHO) potential energy for oxidation and glucose production (GP), we performed a lactate clamp (LC) procedure during rest and moderate intensity exercise. Blood [lactate] was clamped at approximately 4 mM by exogenous lactate infusion. Subjects performed 90 min exercise trials at 65 % of the peak rate of oxygen consumption (V(O(2))(,peak); 65 %), 55 % V(O(2))(,peak) (55 %) and 55 % V(O(2))(,peak) with lactate clamped to the blood [lactate] that was measured at 65 % V(O(2))(,peak) (55 %-LC). Lactate and glucose rates of appearance (R(a)), disappearance (R(d)) and oxidation (R(ox)) were measured with a combination of [3-(13)C]lactate, H(13)CO(3)(-), and [6,6-(2)H(2)]glucose tracers. During rest and exercise, lactate R(a) and R(d) were increased at 55 %-LC compared to 55 %. Glucose R(a) and R(d) were decreased during 55 %-LC compared to 55 %. Lactate R(ox) was increased by LC during exercise (55 %: 6.52 +/- 0.65 and 55 %-LC: 10.01 +/- 0.68 mg kg(-1) min(-1)) which was concurrent with a decrease in glucose oxidation (55 %: 7.64 +/- 0.4 and 55 %-LC: 4.35 +/- 0.31 mg kg(-1) min(-1)). With LC, incorporation of (13)C from tracer lactate into blood glucose (L GNG) increased while both GP and calculated hepatic glycogenolysis (GLY) decreased. Therefore, increased blood [lactate] during moderate intensity exercise increased lactate oxidation, spared blood glucose and decreased glucose production. Further, exogenous lactate infusion did not affect rating of perceived exertion (RPE) during exercise. These results demonstrate that lactate is a useful carbohydrate in times of increased energy demand.

Adult↗

PubMed1994

Glucose and L-lactate metabolism in pregnant and in lactating ewes fed barley- or ground maize-based diets.

The contribution of glucose absorbed from the small intestine to whole-body glucose metabolism was examined in ewes during late pregnancy and early lactation, using diets based on ground barley or ground maize. Glucose and L-lactate turnover in the whole body and the mesenteric-drained viscera were investigated in these ewes using isotope dilution techniques. The net absorption of glucose by the mesenteric-drained viscera and whole-body glucose turnover were unaffected by diet or reproductive status. Arterial and mesenteric venous blood glucose concentrations, arterial and mesenteric venous L-lactate concentrations and whole-body lactate turnover were all significantly higher in lactation than in pregnancy. The whole-body rates of lactate conversion to glucose and to other products were significantly higher in lactation than in pregnancy. Using a two-pool model of whole-body glucose and lactate metabolism, a relatively high percentage of glucose was converted to lactate (64-84%), accounting for 60-80% of whole-body lactate turnover. A model of glucose and lactate metabolism by the mesenteric-drained viscera was constructed. Both the calculated endogenous glucose production and the visceral conversion of glucose to lactate were greater in lactation than in pregnancy when barley was fed. Calculated total glucose absorption was relatively constant, contributing between 26 and 59% of whole-body glucose turnover. Diet had little effect on glucose and lactate metabolism in either the mesenteric-drained viscera or the whole-body of breeding ewes.

Animals↗

PubMed1989

Inhibition of endogenous lactate turnover with lactate infusion in humans.

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-14C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

Carbon Radioisotopes↗

PubMed1992

The effects of the exogenous provision of lactate and the endogenous production of lactate on protein synthesis in the heart.

We have investigated the effects of exogenous addition of lactate and of the stimulation of endogenous production of lactate on protein synthesis in the anterogradely perfused rat heart. In the absence of exogenous lactate, hearts release lactate into the perfusate. At lactate concentrations of 0.2 mM and greater, the heart takes up lactate. The best fit for lactate uptake plotted against exogenous lactate concentration is a rectangular hyperbola with a maximal rate of 220 mumol/2 h per heart (wet wt. about 1 g). Uptake is half-maximal at about 1.3 mM-lactate. The stimulation of protein synthesis also exhibits a rectangular-hyperbolic dependence on exogenous lactate concentration, with maximal stimulation being about 38%. Half-maximal stimulation occurs at about 0.9 mM-lactate. We stimulated endogenous lactate production by perfusion with 2-cyanocinnamate (an inhibitor of mitochondrial pyruvate transport) at concentrations up to 70 microM. Cardiac outputs, intracellular pH and the concentrations of phosphocreatine and the adenine nucleotides were not altered. Atrial protein-synthesis rates were unchanged, but ventricular rates were decreased. We conclude that endogenous lactate production is unlikely to stimulate protein synthesis and that the stimulation of protein synthesis by exogenous lactate is related to its uptake.

Adenine Nucleotides↗

PubMed1995

Characterization of the enhanced transport of L- and D-lactate into human red blood cells infected with Plasmodium falciparum suggests the presence of a novel saturable lactate proton cotransporter.

Human erythrocytes parasitized with the malarial protozoan Plasmodium falciparum showed rates of L-lactate, D-lactate, and pyruvate uptake many fold greater than control cells. Thus it was necessary to work at 0 degrees C to resolve true initial rates of transport. Studies on the dependence of the rate of transport on substrate concentration implied the presence in parasitized cells of both a saturable mechanism blocked by alpha-cyano-4-hydroxycinnamate (CHC) and a nonsaturable mechanism insensitive to CHC. The former was dominant at physiological substrate concentrations with Km values for pyruvate and D-lactate of 2.3 and 5.2 mM, respectively, with no stereoselectivity for L- over D-lactate. CHC was significantly less effective as an inhibitor of lactate transport in parasitized erythrocytes than in uninfected cells, whereas p-chloromercuribenzenesulfonate, a potent inhibitor in control cells, gave little or no inhibition of lactate transport into parasitized erythrocytes. Inhibition of transport into infected cells was also observed with phloretin, furosemide, niflumic acid, stilbenedisulfonate derivatives, and 5-nitro-2-(3-phenylpropylamino)benzoic acid at concentrations similar to those that inhibit the lactate carrier of control erythrocytes. These compounds were more effective inhibitors of the rapid transport of chloride into infected cells than of lactate transport, whereas CHC was more effective against lactate transport. This implies that different pathways are involved in the parasite-induced transport pathways for lactate and chloride. The transport of L-lactate into infected erythrocytes was also inhibited by D-lactate, pyruvate, 2-oxobutyrate, and 2-hydroxybutyrate. The intracellular accumulation of L-lactate at equilibrium was dependent on the transmembrane pH gradient, suggesting a protogenic transport mechanism. Our data are consistent with lactate and pyruvate having direct access to the malarial parasite, perhaps via the proposed parasitophorous duct or some close contact between the host cell and parasite plasma membranes, with transport across the latter by both a proton-linked carrier (CHC-sensitive, saturable, and the major route) and free diffusion of the undissociated acid (CHC-insensitive, unsaturable, and a minor route).

Animals↗

PubMed1979

Lactate elimination in man: effects of lactate concentration and hepatic dysfunction.

Lactate elimination was studied in twenty-six healthy volunteers during primed constant lactate infusion or multiple lactate injection tests, at blood lactate concentrations of 1-8 mmol-1. Although lactate elimination fitted a single exponential curve over a 30 min period, a significant correlation between the rate removal constant (KL) and the peak blood lactate concentration (Lphi) was demonstrated: loge KL = -2.43-0.132 Lphi (P = 0.003, r = 0.63, n = 20) This suggests that lactate removal does not follow first order kinetics over a wide concentration range but becomes saturated at relatively low blood lactate concentrations. Estimates of the lactate distribution volume did not differ significantly at different dosage levels, but remained in the range 270-300 ml kg-1. Skeletal muscle uptake accounted for about 26% of the infused lactate load. Seven patients with well-compensated hepatic cirrhosis were compared with a group of six control subjects during primed constant infusion tests. Fasting and steady state blood lactate concentrations achieved were similar in both groups. A significant prolongation in lactate half-life was demonstrated in the cirrhotics (18.8 +/- 1.4 min (mean +/- SEM) compared to 14.7 +/- 2.2 min; P less than 0.02). Since peripheral uptake of lactate in the forearm was similar in the two groups, this suggests that hepatic lactate uptake was impaired, due either to hepatocyte dysfunction or portal diversion.

Adult↗

PubMed1986

Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise.

O2 insufficiency and other factors increase the rate of lactate production. Significant quantities of lactate are produced under postabsorptive as well as postprandial conditions in resting individuals. In humans during postabsorptive rest, 25-50% of the total carbohydrate combusted appears to pass through the lactate pool. During sustained submaximal (in terms of VO2max) exercise, the rates of lactate production (Ri) and oxidation (Rox) are greatly elevated as compared to rest. However, lactate production and oxidation increase relatively less than O2 consumption during moderate-intensity exercise. Because the lactate production index (RiI = Ri/VO2) decreases during submaximal, moderate-intensity exercise compared to rest, it is concluded that skeletal muscle and other sites of lactate production are effectively oxygenated. Alterations in the levels of circulating catecholamines can affect levels and turnover rates of glucose and lactate. In pure red dog gracilis muscle in situ and in the healthy and myocardium in vivo, contraction results in glycolysis and lactate production. This production of lactate occurs despite an apparent abundance of O2. Similarly, glucose catabolism in the human brain results in lactate production. The formation of lactate under fully aerobic conditions of rest and exercise represents an important mechanism by which different tissues share a carbon source (lactate) for oxidation and other processes such as gluconeogenesis. This mechanism has been termed the lactate shuttle.

Aerobiosis↗

PubMed1997

[The pharmacokinetics of D-lactate, L-lactate and acetate in humans].

In this study, the pharmacokinetics of D-lactate, L-lactate and acetate were investigated in 36 adult surgical patients. After induction of general anaesthesia, the subjects received intravenous injection of either 5 mmoles of D-lactate and 5 mmoles of L-lactate simultaneously (Group DL), 10 mmoles of L-lactate (Group L), or 10 mmoles of acetate (Group A). Serial arterial blood samples were obtained before the injection, and 3, 5, 7, 9 and 11 minutes after the infusion of each preparation. Plasma concentrations of D-lactate, L-lactate and acetate were measured by high performance liquid chromatography, enzymatic analysis and spectrophotometry. The pharmacokinetic parameters; distribution volume (Vd) and half-life (t1/2) were calculated with a one-compartment model from the incremental plasma concentration decay curve after administration. In Group DL, there were no differences between D-lactate and L-lactate in Vd and t1/2. Also, between L-lactate in Group DL and that in Group L, there were no differences in Vd and t1/2. The Vd and T1/2 of acetate, however, were smaller than those of L-lactate in Group L. We conclude that the pharmacokinetics of D-lactate is similar to those of L-lactate, and that acetate may be metabolized more rapidly than L-lactate.

Acetic Acid↗

PubMed2003

Gastric PgCO2 and Pg-aCO2 gap are related to D-lactate and not to L-lactate levels in patients with septic shock.

OBJECTIVE: Intestinal ischemia causes an increase in lactate production and gastric intramucosal carbon dioxide partial pressure (PgCO(2)). However, no linear relationship between systemic l-lactate levels and gastric tonometry during intestinal ischemia has been found, probably since l-lactate is rapidly cleared from the circulation by the liver. In contrast, the rate of d-lactate clearance from the circulation by the liver is considerably lower than that of l-lactate, and d-lactate may therefore be more closely related to measurements of gastric tonometry than l-lactate values. DESIGN AND SETTING: Prospective, observational study in a university-affiliated mixed intensive care unit. SUBJECTS: Twenty critically ill patients with septic shock. MEASUREMENTS AND RESULTS: During the first 24 h of admission to the intensive care unit at least two blood samples were taken for d- and l-lactate measurements and arterial blood gases, Simultaneously, gastric PgCO(2) was measured using capnographic tonometry. The intramucosal-arterial PCO(2) gap was calculated using gastric intramucosal PgCO(2) and arterial PCO(2) from arterial blood. d-Lactate was significantly correlated to PgCO(2) values and to the mucosal-arterial PCO(2) gap. There was no relationship between l-lactate and PgCO(2) or the mucosal-arterial PCO(2) gap. d-lactate and l-lactate values were significantly correlated. CONCLUSIONS: During sepsis intestinal production of d-lactate is related to gastric intramucosal PCO(2). No such relationship was found between l-lactate values and PgCO(2)

Acid-Base Equilibrium↗

PubMed1992

Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin.

Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [SI] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that SI and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between SI and basal lactate levels (r = -.56). Moreover, a significant and positive relationship was found between SI and incremental lactate area under the curve (reflecting acute lactate production) (r = .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, SI accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Homeostatic responses to water deprivation or hemorrhage in lactating and non-lactating Bedouin goats.

Three lactating and three non-lactating black Bedouin goats were subjected to four days of water deprivation or to hemorrhage. Four days of water deprivation caused body wt losses of 32 and 23% and plasma volume losses of 30 and 34% in lactating and non-lactating goats respectively. Plasma osmolality increased 17 and 15% in lactating and non-lactating goats. Plasma arginine vasopressin concentration rose from about 5 pg/ml to a mean of 36 pg/ml. Plasma renin activity increased from about 0.7 ng/ml/hr to a mean of 3.45 ng/ml/hr in lactating and to 3.15 ng/ml/hr in non-lactating goats. At 4.5 hr post-rehydration plasma osmolality and plasma vasopressin concentration were back to normal in non-lactating, but still elevated in lactating goats. Plasma renin activity increased after rehydration. Rapid blood volume loss of 21-28% increased plasma vasopressin concentration to 16-35 pg/ml in non-lactating and to 70 or greater than 500 pg/ml in lactating goats. It is concluded that black Bedouin goats are well adapted to endure severe dehydration and rapid rehydration, but that they (especially lactating animals) react strongly to rapid volume depletion.

Animals↗

PubMed2004

Partial reconstruction of in vitro gluconeogenesis arising from mitochondrial l-lactate uptake/metabolism and oxaloacetate export via novel L-lactate translocators.

In the light of the occurrence of L-lactate dehydrogenase inside the mitochondrial matrix, we looked at whether isolated rat liver mitochondria can take up and metabolize L-lactate, and provide oxaloacetate outside mitochondria, thus contributing to a partial reconstruction of gluconeogenesis in vitro. We found that: (1) L-lactate (10 mM), added to mitochondria in the presence of a cocktail of glycolysis/gluconeogenesis enzymes and cofactors, can lead to synthesis of glyceraldehyde-3-phosphate at a rate of about 7 nmol/min per mg mitochondrial protein. (2) Three novel translocators exist to mediate L-lactate traffic across the inner mitochondrial membrane. An L-lactate/H+ symporter was identified by measuring fluorimetrically the rate of endogenous pyridine nucleotide reduction. Consistently, L-lactate oxidation was found to occur with P/O ratio=3 (where P/O ratio is the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation) and with generation of membrane potential. Proton uptake, which occurred as a result of addition of L-lactate to RLM together with electron flow inhibitors, and mitochondrial swelling in ammonium L-lactate solutions were also monitored. L-Lactate/oxaloacetate and L-lactate/pyruvate anti-porters were identified by monitoring photometrically the appearance of L-lactate counter-anions outside mitochondria. These L-lactate translocators, which are distinct from the monocarboxylate carrier, were found to differ from each other in V(max) values and in inhibition and pH profiles, and proved to regulate mitochondrial L-lactate metabolism in vitro. The role of lactate/mitochondria interactions in gluconeogenesis is discussed.

Animals↗

PubMed1994

Maternal protein reserves and their influence on lactational performance in rats. 3. The effects of dietary protein restriction and stage of lactation on milk composition.

The effects of severe protein restriction following parturition on the changes in rat milk composition during lactation were investigated using multiparous female Sprague-Dawley rats caged individually following mating and offered a high-protein diet (H; 215 g crude protein (N x 6.25; CP)/kg dry matter (DM)) ad lib. until parturition. Following parturition, half the females continued to receive diet H, whilst the remainder were offered a diet low in protein (L; 90 g CP/kg DM) ad lib. On days 2, 4, 8 and 12 of lactation groups of females from both dietary treatments were used to provide a milk sample. Milk samples were analysed for their lactose (enzymically), protein (binding to Coomassie blue), lipid (gravimetrically) and mineral (spectrophotometrically) contents. The milk lactose concentration of group H increased with stage of lactation (r2 0.85, P < 0.001). Such an increase was prevented by diet L, and from day 8 of lactation the milk lactose of group L was lower (P < 0.05) than in group H. Group H milk protein concentration did not change during lactation and averaged 90.7 mg/g. Dietary protein restriction reduced the milk protein concentration of group L so that on days 2, 4 and 12 of lactation it was lower (P < 0.05) than that of group H. On day 8 of lactation the milk protein concentration of group L had increased (P < 0.05) and was comparable with that of group H. For group H, milk lipid averaged 166.8 mg/g and was generally unchanged during lactation. Diet L increased (P < 0.01) the milk lipid concentration (205.5 mg/g) compared with diet H and this was also significant on days 4 and 8 of lactation (P < 0.05). Group L milk lipid concentration also increased between days 4 and 8 of lactation (P < 0.05). Milk Na concentration declined during lactation in both dietary groups (P < 0.01) but was unaffected by dietary treatment. Both milk Ca and P concentrations increased (P < 0.01) during lactation in both dietary groups, whilst protein restriction also increased the Ca and P concentrations (P < 0.05). Milk K and Mg concentrations were unaffected by dietary treatment or stage of lactation. This significant alteration in the milk composition of severely protein-restricted dams, while possibly favouring the disposal of greater quantities of energy-yielding nutrients, suggests that equations developed for the estimation of milk production in rats cannot be used under such conditions.

Animals↗

PubMed1990

The cDNA and protein sequences of mouse lactate dehydrogenase B. Molecular evolution of vertebrate lactate dehydrogenase genes A (muscle), B (heart) and C (testis).

Mouse lactate dehydrogenase-B cDNAs were isolated from cDNA libraries of macrophage (ICR strain) and thymus (F1 hybrid of C57BL/6 and CBA strains), and their nucleotide sequences determined. The lactate dehydrogenase-B cDNA insert of thymus clone mB188 consists of the protein-coding sequence (1002 nucleotides), the 5' (46 nucleotides) and 3' (190 nucleotides) non-coding regions, and poly(A) tail (19 nucleotides), while macrophage clone mB168 contains a partial lactate dehydrogenase cDNA insert from codon no. 55 to the poly(A) tail. Seven silent nucleotide substitutions at codon no. 142, 143, 186, 187, 241, 285 and 292, as well as a single nucleotide change in the 3' non-coding region, were found between these different strains of mice. The predicted sequence of 333 amino acids, excluding initiation methionine, was confirmed by sequencing and/or compositional analyses of a total of 103 (31%) amino acids from tryptic peptides of mouse lactate dehydrogenase-B protein. The nucleotide sequence of the mouse coding region for lactate dehydrogenase B shows 86% identity with that of the human isoenzyme, and only eight of the 139 nucleotide differences resulted in amino acid substitutions at residues 10, 13, 14, 17, 52, 132, 236 and 317. The rates of nucleotide substitutions at synonymous and nonsynonymous sites in the mammalian lactate dehydrogenase genes are calculated. The rates of synonymous substitutions for lactate dehydrogenase genes A (muscle) and B (heart) are considerably higher than the average rate computed from human and rodent genes. The rates of nonsynonymous substitutions for lactate dehydrogenase genes A (muscle) and B (heart), particularly the latter, are highly conservative. The rates of synonymous and nonsynonymous substitutions for the lactate dehydrogenase-C gene are about the same as the average rates for mammalian genes. A phylogenetic tree of vertebrate lactate dehydrogenase protein sequences is constructed. In agreement with the previous results, this analysis further indicates that lactate dehydrogenase-C gene branched off earlier than did lactate dehydrogenase-A and lactate dehydrogenase-B genes.

Amino Acid Sequence↗