-
Cell Metabolism Apr 2018Once thought to be a waste product of anaerobic metabolism, lactate is now known to form continuously under aerobic conditions. Shuttling between producer and consumer... (Review)
Review
Once thought to be a waste product of anaerobic metabolism, lactate is now known to form continuously under aerobic conditions. Shuttling between producer and consumer cells fulfills at least three purposes for lactate: (1) a major energy source, (2) the major gluconeogenic precursor, and (3) a signaling molecule. "Lactate shuttle" (LS) concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signaling. In medicine, it has long been recognized that the elevation of blood lactate correlates with illness or injury severity. However, with lactate shuttle theory in mind, some clinicians are now appreciating lactatemia as a "strain" and not a "stress" biomarker. In fact, clinical studies are utilizing lactate to treat pro-inflammatory conditions and to deliver optimal fuel for working muscles in sports medicine. The above, as well as historic and recent studies of lactate metabolism and shuttling, are discussed in the following review.
Topics: Animals; Brain; Gluconeogenesis; Glycolysis; Humans; Lactic Acid; Oxidation-Reduction
PubMed: 29617642
DOI: 10.1016/j.cmet.2018.03.008 -
Asian Pacific Journal of Cancer... 2014Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug... (Review)
Review
Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Lactic Acid; Nanoparticles; Neoplasms; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 24568455
DOI: 10.7314/apjcp.2014.15.2.517 -
BioMed Research International 2020Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some... (Review)
Review
Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.
Topics: Acidosis; Animals; Humans; Lactic Acid; Metabolic Networks and Pathways; Metabolome
PubMed: 32685468
DOI: 10.1155/2020/3419034 -
Frontiers in Immunology 2021Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling... (Review)
Review
Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.
Topics: Acetyl Coenzyme A; Animals; Epigenesis, Genetic; Histones; Humans; Lactic Acid; Tumor Microenvironment
PubMed: 34177945
DOI: 10.3389/fimmu.2021.688910 -
Anesthesiology Apr 2021
-
Seminars in Cancer Biology Nov 2022The evolutionary pressure for life transitioning from extended periods of hypoxia to an increasingly oxygenated atmosphere initiated drastic selections for a variety of... (Review)
Review
The evolutionary pressure for life transitioning from extended periods of hypoxia to an increasingly oxygenated atmosphere initiated drastic selections for a variety of biochemical pathways supporting the robust life currently present on the planet. First, we discuss how fermentative glycolysis, a primitive metabolic pathway present at the emergence of life, is instrumental for the rapid growth of cancer, regenerating tissues, immune cells but also bacteria and viruses during infections. The 'Warburg effect', activated via Myc and HIF-1 in response to growth factors and hypoxia, is an essential metabolic and energetic pathway which satisfies nutritional and energetic demands required for rapid genome replication. Second, we present the key role of lactic acid, the end-product of fermentative glycolysis able to move across cell membranes in both directions via monocarboxylate transporting proteins (i.e., MCT1/4) contributing to cell-pH homeostasis but also to the complex immune response via acidosis of the tumor microenvironment. Importantly lactate is recycled in multiple organs as a major metabolic precursor of gluconeogenesis and energy source protecting cells and animals from harsh nutritional or oxygen restrictions. Third, we revisit the Warburg effect via CRISPR-Cas9 disruption of glucose-6-phosphate isomerase (GPI-KO) or lactate dehydrogenases (LDHA/B-DKO) in two aggressive tumors (melanoma B16-F10, human adenocarcinoma LS174T). Full suppression of lactic acid production reduces but does not suppress tumor growth due to reactivation of OXPHOS. In contrast, disruption of the lactic acid transporters MCT1/4 suppressed glycolysis, mTORC1, and tumor growth as a result of intracellular acidosis. Finally, we briefly discuss the current clinical developments of an MCT1 specific drug AZ3965, and the recent progress for a specific in vivo MCT4 inhibitor, two drugs of very high potential for future cancer clinical applications.
Topics: Animals; Humans; Monocarboxylic Acid Transporters; Symporters; Cell Line, Tumor; Lactic Acid; Virus Diseases; Bacteria; Hypoxia
PubMed: 35820598
DOI: 10.1016/j.semcancer.2022.07.004 -
Ugeskrift For Laeger Feb 2019Accumulation of muscle lactate and lowering of muscle pH during intense exercise do not per se cause fatigue during exercise, but it appears that they contribute to... (Review)
Review
Accumulation of muscle lactate and lowering of muscle pH during intense exercise do not per se cause fatigue during exercise, but it appears that they contribute to fatigue development in humans. This may be related to lowered muscle pH causing greater release of K+ from the contracting muscles and sensation of fatigue. Training elevates the capacity to release lactate and H+ as well as to buffer H+, probably contributing to the enhanced performance during intense exercise after a training period. In this review, we discuss the role of lactate and H+ for intense exercise performance in humans.
Topics: Exercise; Fatigue; Humans; Lactic Acid; Muscle Fatigue; Muscle, Skeletal
PubMed: 30821240
DOI: No ID Found -
Critical Care (London, England) Aug 2016The time course of blood lactate levels could be helpful to assess a patient's response to therapy. Although the focus of published studies has been largely on septic... (Review)
Review
BACKGROUND
The time course of blood lactate levels could be helpful to assess a patient's response to therapy. Although the focus of published studies has been largely on septic patients, many other studies have reported serial blood lactate levels in different groups of acutely ill patients.
METHODS
We performed a systematic search of PubMed, Science Direct, and Embase until the end of February 2016 plus reference lists of relevant publications. We selected all observational and interventional studies that evaluated the capacity of serial blood lactate concentrations to predict outcome. There was no restriction based on language. We excluded studies in pediatric populations, experimental studies, and studies that did not report changes in lactate values or all-cause mortality rates. We separated studies according to the type of patients included. We collected data on the number of patients, timing of lactate measurements, minimum lactate level needed for inclusion if present, and suggested time interval for predictive use.
RESULTS
A total of 96 studies met our criteria: 14 in general ICU populations, five in general surgical ICU populations, five in patients post cardiac surgery, 14 in trauma patients, 39 in patients with sepsis, four in patients with cardiogenic shock, eight in patients after cardiac arrest, three in patients with respiratory failure, and four in other conditions. A decrease in lactate levels over time was consistently associated with lower mortality rates in all subgroups of patients. Most studies reported changes over 6, 12 or 24 hrs, fewer used shorter time intervals. Lactate kinetics did not appear very different in patients with sepsis and other types of patients. A few studies suggested that therapy could be guided by these measurements.
CONCLUSIONS
The observation of a better outcome associated with decreasing blood lactate concentrations was consistent throughout the clinical studies, and was not limited to septic patients. In all groups, the changes are relatively slow, so that lactate measurements every 1-2 hrs are probably sufficient in most acute conditions. The value of lactate kinetics appears to be valid regardless of the initial value.
Topics: Critical Illness; Humans; Intensive Care Units; Lactic Acid; Sepsis
PubMed: 27520452
DOI: 10.1186/s13054-016-1403-5 -
PloS One 2017This study assessed the effectiveness of water immersion to the shoulders in enhancing blood lactate removal during active and passive recovery after short-duration... (Randomized Controlled Trial)
Randomized Controlled Trial
This study assessed the effectiveness of water immersion to the shoulders in enhancing blood lactate removal during active and passive recovery after short-duration high-intensity exercise. Seventeen cyclists underwent active water- and land-based recoveries and passive water and land-based recoveries. The recovery conditions lasted 31 minutes each and started after the identification of each cyclist's blood lactate accumulation peak, induced by a 30-second all-out sprint on a cycle ergometer. Active recoveries were performed on a cycle ergometer at 70% of the oxygen consumption corresponding to the lactate threshold (the control for the intensity was oxygen consumption), while passive recoveries were performed with subjects at rest and seated on the cycle ergometer. Blood lactate concentration was measured 8 times during each recovery condition and lactate clearance was modeled over a negative exponential function using non-linear regression. Actual active recovery intensity was compared to the target intensity (one sample t-test) and passive recovery intensities were compared between environments (paired sample t-tests). Non-linear regression parameters (coefficients of the exponential decay of lactate; predicted resting lactates; predicted delta decreases in lactate) were compared between environments (linear mixed model analyses for repeated measures) separately for the active and passive recovery modes. Active recovery intensities did not differ significantly from the target oxygen consumption, whereas passive recovery resulted in a slightly lower oxygen consumption when performed while immersed in water rather than on land. The exponential decay of blood lactate was not significantly different in water- or land-based recoveries in either active or passive recovery conditions. In conclusion, water immersion at 29°C would not appear to be an effective practice for improving post-exercise lactate removal in either the active or passive recovery modes.
Topics: Adult; Bicycling; Cross-Over Studies; Double-Blind Method; Humans; Immersion; Lactic Acid; Oxygen Consumption; Physical Exertion
PubMed: 28877225
DOI: 10.1371/journal.pone.0184240 -
Intensive Care Medicine Jan 2019
Topics: Humans; Lactic Acid; Liver Diseases; Metabolic Clearance Rate; Sepsis
PubMed: 29754310
DOI: 10.1007/s00134-018-5213-x