Disease relevance of lactic acid

• L-Lactate was elevated in pouchitis outputs, but differences in stool culture counts, mucosal histology, fecal concentration, assimilation or production of ammonia, nitrogen excretion, pH, and osmolality were not found [1].
• In the roots of barley and other cereals, hypoxia induces a set of five isozymes of L-lactate dehydrogenase [LDH; (S)-lactate:NADH oxidoreductase, EC 1.1.1.27] [2].
• Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle [3].
• To mimic in vivo ischemia, we exposed astrocytes to NaN3 and 0 glucose saline containing L-lactate and glutamate with increased [K+] and decreased [Na+], [Ca2+], and pH [4].
• Studies on the mechanism of Mycobacterium smegmatis L-lactate oxidase. 5-Deazaflavin mononucleotide as a coenzyme analogue [5].
• In response to hypoglycemia, epinephrine increased 10-fold, and the fractional release of lactate in SM doubled (P < 0.0001) [6].
• The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator) [7].

Psychiatry related information on lactic acid

• Cerebral blood flow changes during sodium-lactate-induced panic attacks [8].
• Linear response ranges of up to 40 mM for glucose and 25 mM for L-lactate, in combination with 95% response times of < 30 s, were realized [9].
• L-lactate uptake by rat liver. Effect of food deprivation and substrate availability [10].
• Macroscopic disorientation of the structure of the 2 over 2 + 1 braided self-reinforced polylactic acid polymer stents began before 1 month, while 1 over 1 braided stents retained their construction [11].
• RESULTS: Polylactic acid injections led to a significant improvement in facial lipoatrophy, confirmed by the patients' facial lipoatrophy self-perception and by the ultrasonographic evaluation [12].

High impact information on lactic acid

• Serum L-lactate level was normal, but high-resolution proton nuclear magnetic resonance spectrums of the patient's serum showed a high concentration of lactate [13].
• Further investigation suggested that these CD dimers inhibit the activity of L-lactate dehydrogenase and citrate synthase at least in part by disruption of protein-protein aggregation [14].
• Under voltage-clamp conditions, no significant electrogenic current was associated with H(+)-coupled L-lactate influx, and membrane potential (-75 to +75 mV) had no effect on the degree of acidification produced by 30 mmol/L [L-]o, indicating that L-lactate influx was predominantly nonelectrogenic [3].
• To examine the mechanisms of transsarcolemmal L-lactate movement in the heart, isolated guinea pig ventricular myocytes were loaded with the fluorescent H+ or K+ indicators, carboxy SNARF-1 or PBFI, respectively, under whole-cell patch-clamp conditions [3].
• These results suggest that transcatheter arterial chemoembolization with the use of polylactic acid microspheres containing ACR is a useful tumor-targeting chemotherapy and is effective in the treatment of hepatocellular carcinoma [15].

Chemical compound and disease context of lactic acid

• The allosteric effect of fructose 1,6-bisphosphate (Fru-1,6-P2) on L-lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from Thermus caldophilus GK24 was studied by means of 1H NMR analyses [16].
• The role of glycine 99 in L-lactate monooxygenase from Mycobacterium smegmatis [17].
• A mutant form of L-lactate oxidase (LOX) from Aerococcus viridans in which alanine 95 was replaced by glycine was constructed as a mimic of L-lactate monooxygenase but proved instead to be a mimic of the long chain alpha-hydroxyacid oxidase from rat kidney [18].
• On modification of arginine residues with 2,3-butanedione, the Thermus caldophilus L-lactate dehydrogenase is converted to an activated form that is independent of an allosteric effector, fructose 1,6-bisphosphate (Fru-1,6-P2) [19].
• The behavior of this enzyme toward halogeno substrates is therefore similar to that of baker's yeast L-lactate dehydrogenase and in part different from that of Mycobacterium smegmatis lactate oxidase and porcine kidney D-amino-acid oxidase [20].

Biological context of lactic acid

• The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate [21].
• The activation energy of L-lactate transport into hepatocytes was 58 kJ mol-1, and measured rates of transport at 37 degrees C were considerably greater than those required for maximal rates of gluconeogenesis [22].
• We evaluated the effects of unsubstituted and hydroxymonocarboxylic acids on the kinetics of Na+-dependent L-lactate uptake in brush-border membrane vesicles prepared from the whole cortex of rabbit kidney [23].
• Amino acid sequence analysis of two tryptic fragments of the purified material showed greater than 95% homology with sequences 179-194 and 319-328 of the M chain of human L-lactate dehydrogenase [24].
• L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family [25].

Anatomical context of lactic acid

• However, in myocytes loaded with PBFI, no significant increase in [K+]i was detected during exposure to 30 mmol/L [L-]o, suggesting that only a minor component, if any, of L-lactate influx was cotransported or codiffused with K+ [3].
• A rabbit erythrocyte membrane protein associated with L-lactate transport [26].
• L(+)-Lactate binding to preparations of rat hepatocyte plasma membranes [27].
• In this paper, we describe for the first time the existence of organic anion transport in T lymphocytes, exemplified by the transmembrane transport of the anions L-lactate and the Ca2+ indicator fluo-3 [28].
• The 22-h fasting plasma portal vein concentrations of D-glucose, L-lactate, and L-alanine were 4.8 +/- 0.03, 0.81 +/- 0.06, and 0.20 +/- 0.03 mM, respectively (n = 5) [29].

Associations of lactic acid with other chemical compounds

• These studies indicated that position 8 of flavin bound to melilotate hydroxylase, D-amino acid oxidase, old yellow enzyme, p-OH-benzoate hydroxylase, and flavodoxin is accessible to solvent, while position 8 on L-lactate oxidase, glucose oxidase, putrescine oxidase, and riboflavin-binding protein appears to be inaccessible [30].
• Finally, addition of L-lactate to vesicles under Na+ equilibrium conditions failed to generate an inside-positive membrane potential as monitored by 3,3'-dipropylthiodicarbocyanine iodide fluorescence quenching, arguing against Na+-L-lactate cotransport by an electrogenic process [31].
• The transport of L-lactate into infected erythrocytes was also inhibited by D-lactate, pyruvate, 2-oxobutyrate, and 2-hydroxybutyrate [32].
• Glucagon and L-epinephrine stimulate gluconeogenesis from 20 mM L-lactate, the effect being about 3 times greater in liver cells from fed rats than in those from fasted rats [33].
• D-Lactate dehydrogenase and D-mandelate dehydrogenase were co-eluted on gel filtration, as were L-lactate dehydrogenase and L-mandelate dehydrogenase [34].
• Inhibition of lactate dehydrogenase by using oxamate also prevented the angiogenic effects of lactate [35].
• In tumor voxels where both could be measured, the glucose-induced increase in lactate showed no spatial correlation with the decrease in pHe [36].
• Metformin activates AMPK in GCs, stimulating lactate production and increasing phospho-ACC [37].

Gene context of lactic acid

• Structures of the PutA PRODH domain complexed with competitive inhibitors acetate (K(i) = 30 mM), L-lactate (K(i) = 1 mM), and L-tetrahydro-2-furoic acid (L-THFA, K(i) = 0.2 mM) have been determined to high-resolution limits of 2.1-2.0 A [38].
• The DLD gene was cloned by complementation for growth on D-, L-lactate in the strain WWF18-3D, carrying both a CYB2 disruption and the dld mutation [39].
• We constructed a metabolically engineered Saccharomyces cerevisiae that has both pyruvate decarboxylase genes (PDC1 and PDC5) disrupted in the genetic background to express two copies of the bovine L-lactate dehydrogenase (LDH) gene [40].
• Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate [41].
• The predicted amino acid sequence of lldA is homologous to that of E. coli lldD and of other prokaryotic and eukaryotic flavin mononucleotide-containing enzymes that catalyze the oxidation of L-lactate and other small alpha-hydroxy acids [42].
• Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function [43].
• We identified monocarboxylate transporter 1 (MCT1) as the prominent path for lactate uptake by a human cervix squamous carcinoma cell line that preferentially utilized lactate for oxidative metabolism [44].
• Lactate specifically induces internalization of GPR81 after receptor activation [45].

Analytical, diagnostic and therapeutic context of lactic acid

• METHODS: L-lactate uptake into and efflux from isolated jejunal basolateral membrane vesicles was investigated at room temperature using rapid filtration techniques [46].
• Studies on the active center of D- and L-lactate dehydrogenases using oxamate-diaminohexyl-Sepharose affinity chromatography [47].
• A single dose of polylactic acid microspheres containing ACR (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 doses (a total of 160 treatments) in 62 patients [15].
• For this purpose, we combined bilateral VMH microdialysis perfusion (metabolically active L-lactate or its nonmetabolizable D-isomer) with a euglycemic-hypoglycemic clamp in conscious chronically catheterized Sprague-Dawley rats [48].
• Crystallization and preliminary crystallographic analysis at low resolution of the allosteric L-lactate dehydrogenase from Lactobacillus casei [49].

References