Lactate Molecules Research Articles

Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.

The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells.

A Bifunctional Wearable Sensor Based on a Nanoporous Membrane for Simultaneous Detection of Sweat Lactate and Temperature.

Wearable sensors for non-invasive, real-time detection of sweat lactate have far-reaching implications in the fields of health care and exercise physiological responses. Here, we propose a wearable electrochemical sensor with gold nanoelectrode arrays fabricated on the nanoporous polycarbonate (PC) membrane by encapsulating lactate oxidase (LOx) in chitosan (CS) hydrogel for detecting body temperature and sweat lactate concurrently. Flexible gold nanoporous electrodes not only enhance electrode area but also offer a nanoconfined space to accelerate the catalytic reaction of LOx and control substrate concentration on the surface of LOx to decrease substrate inhibition. The proposed sensor has a long durability of 13 days and better selectivity for the detection of sweat lactate over a wide linear range (0.01-35 mM) with a low detection limit (0.144 μM). Furthermore, temperature-dependent transmembrane currents passing through the sensor are used to estimate body temperature. We then use multiple linear regression to adjust the effect of temperature on lactate detection and succeed in monitoring lactate molecules in sweat and body temperature during exercise.

Near-infrared absorption and emission probes with optimal connection bridges for live monitoring of NAD(P)H dynamics in living systems

Two NAD(P)H-biosensing probes consisting of 1,3,3-trimethyl-3H-indolium and 3-quinolinium acceptors, linked by thiophene, A, and 3,4-ethylenedioxythiophene, B, bridges are detailed. We synthesized probes C and D, replacing the thiophene connection in probe A with phenyl and 2,1,3-benzothiadiazole units, respectively. Probe E was prepared by substituting probe A's 3-quinolinium unit with a 1-methylquinoxalin-1-ium unit. Probe solutions are non-fluorescent but in the presence of NADH, exhibit near-infrared fluorescence at 742.1 nm and 727.2 nm for probes A and B, respectively, and generate absorbance signals at 690.6 nm and 685.9 nm. In contrast, probes C and D displayed pronounced interference from NADH fluorescence at 450 nm, whereas probe E exhibited minimal fluorescence alterations in response to NAD(P)H. Pre-treatment of A549 cells with glucose in the presence of probe A led to a significant increase in fluorescence intensity. Additionally, subjecting probe A to lactate and pyruvate molecules resulted in opposite changes in NAD(P)H levels, with lactate causing a substantial increase in fluorescence intensity, conversely, pyruvate resulted in a sharp decrease. Treatment of A549 cells with varying concentrations of the drugs cisplatin, gemcitabine, and camptothecin (5, 10, and 20 µM) led to a concentration-dependent increase in intracellular fluorescence intensity, signifying a rise in NAD(P)H levels. Finally, fruit fly larvae were treated with different concentrations of NADH and cisplatin illustrating applicability to live organisms. The results demonstrated a direct correlation between fluorescence intensity and the concentration of NADH and cisplatin, respectively, further confirming the efficacy of probe A in sensing changes in NAD(P)H levels within a whole organism.

PVF composite conductive nanofibers-based organic electrochemical transistors for lactate detection in human sweat

The detection of lactate and other bioactive molecules is of great significance in biological research, medical testing, and environmental monitoring. Organic electrochemical transistors are a kind of biosensor devices, which can convert biological signals into electrical signals. In recent years, fiber-based organic electrochemical transistors (FECTs) provide a new approach for the construction of flexible wearable biosensors, promoting greatly the development of flexible wearable electronic products. In this study, a multilayer composite electrode was first prepared by incorporating MXene and PEDOT:PSS onto electrospun oriented polyvinyl formal (PVF) nanofiber bundle, and then assembled into FECT with high sensitivity and selectivity. Meanwhile, a wearable real-time monitoring platform was built to detect the lactate concentrations in human sweat. The results showed that MXene could act as a bridge between PEDOT:PSS and PVF, and the sensing performance of PVF/MXene/PEDOT:PSS-based FECT was enhanced obviously. It had a wide linear response range of 1 nM-100 mM, a sensitivity of 0.442 NCR/decade, a quick response time of 0.5 s, a low detection concentration, an excellent reproducibility, and a superior anti-interference characteristic. Therefore, this work provided more possibilities for the development of wearable biosensor.

Heterocyclic and non-heterocyclic arena of monocarboxylate transporter inhibitors to battle tumorigenesis.

Monocarboxylate transporters (MCTs) have gained significant attention in cancer research due to their critical role in tumour metabolism. MCTs are legends for transporting lactate molecules in cancer cells, an oncometabolite and waste product of glycolysis, acting as an indispensable factor of tumour proliferation. Targeting MCTs with inhibitors has emerged as a promising strategy to combat tumorigenesis. This article summarizes the most recent research on MCT inhibitors in preventing carcinogenesis, covering both heterocyclic and non-heterocyclic compounds. Heterocyclic and non-heterocyclic compounds such as pteridine, pyrazole, indole, flavonoids, coumarin derivatives and cyanoacetic acid derivatives have been reported as potent MCT inhibitors. We examine the molecular underpinnings of MCTs in cancer metabolism, the design and synthesis of heterocyclic and non-heterocyclic MCT inhibitors, their impact on tumour cells and the microenvironment and their potential as therapeutic agents. Moreover, we explore the challenges associated with MCT inhibitor development and propose future directions for advancing this field. This write-up aims to provide researchers, scientists and clinicians with a comprehensive understanding of the heterocyclic and non-heterocyclic MCT inhibitors and their potential in combating tumorigenesis.

Monitoring lactate with a fluorescent sensor

When organisms break down glucose in low-oxygen environments, the end product is lactate. Most ways to measure this metabolite—to monitor athletic performance or diagnose diseases, for example—depend on enzymes. Now, researchers report a DNA aptamer that can bind l -lactate at physiological levels ( Angew. Chem., Int. Ed. 2023, DOI: 10.1002/anie.202212879 ). Detection based on DNA aptamers , short sequences with a stem-loop structure that can bind other molecules, tends to be more temperature stable and reversible than enzymatic methods. A team led by Juewen Liu of the University of Waterloo used in vitro selection to develop an aptamer that binds to l -lactate when magnesium is present. According to Liu, the Mg 2+ ions may form a bridge between the negatively charged DNA and small, negatively charged lactate molecules. By adding a fluorophore and an antisense strand with a fluorescence quencher, the researchers turned the aptamer into a fluorescent

Evaluation of Hydroxycarboxylic Acid Receptor 1 (HCAR1) as a Building Block for Genetically Encoded Extracellular Lactate Biosensors.

The status of lactate has evolved from being considered a waste product of cellular metabolism to a useful metabolic substrate and, more recently, to a signaling molecule. The fluctuations of lactate levels within biological tissues, in particular in the interstitial space, are crucial to assess with high spatial and temporal resolution, and this is best achieved using cellular imaging approaches. In this study, we evaluated the suitability of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1, formerly named GPR81), as a basis for the development of a genetically encoded fluorescent lactate biosensor. We used a biosensor strategy that was successfully applied to molecules such as dopamine, serotonin, and norepinephrine, based on their respective G-protein-coupled receptors. In this study, a set of intensiometric sensors was constructed and expressed in living cells. They showed selective expression at the plasma membrane and responded to physiological concentrations of lactate. However, these sensors lost the original ability of HCAR1 to selectively respond to lactate versus other related small carboxylic acid molecules. Therefore, while representing a promising building block for a lactate biosensor, HCAR1 was found to be sensitive to perturbations of its structure, affecting its ability to distinguish between related carboxylic molecules.

Front Cover: Combined use of β‐cyclodextrin and ionic liquid as electrolyte additives in EKC for separation and determination of carob's phenolics—A study of the synergistic effect

DOI: 10.1002/elps.202100085 The front cover picture demonstrates the electrophoretic separation of carob phenolics by the use of a novel dual electrophoretic system based on the combined use of β-CD and ionic liquid (IL) as electrolyte additives. In particular, a capillary electrophoresis column filled with β-CD and IL (L-alanine tert butyl ester lactate) molecules is demonstrated. Both β-CD and IL play a significant role in the separation process, allowing the complete separation of the target analytes through their synergistic effect. Behind the column, as a background, the electropherogram obtained under the optimum separation conditions is displayed.

How substituent effects influence the thermodynamics and kinetics of gas-phase transesterification of alkyl lactates to lactide using TiO2/SiO2

Lactide, a crucial precursor of the bioplastic polylactic acid, was obtained through the gas-phase transesterification of alkyl lactates using a 5 wt% TiO2/SiO2 catalyst as an alternative to the conventional liquid-phase process. Lactide selectivity above 80% was achieved at 220 °C but conversion was thermodynamically limited at around 50% for all alkyl lactates. The nature of the ester alkyl chain had minimal impact of the thermodynamics of the reaction, but significantly influenced its kinetics. The Taft equation indicated that this kinetic effect was due to the polarity of the alkyl chain. Mechanistic studies indicated that lactide formed via a Langmuir-Hinshelwood mechanism involving two lactate molecules. The derived kinetic expression was fitted to experimental data of methyl lactate transesterification, resulting in a reduced chi-squared of 0.99 and an activation energy of 89.8 kJ·mol−1. Initial rate kinetics confirmed that the proposed mechanism was valid for other alkyl lactate species.

Energetic and thermodynamical aspects of the cyclodextrins-cannabidiol complex in aqueous solution: a molecular-dynamics study.

Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, β, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-β-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and β-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.

Assessment of effect of chronic alcohol intoxication on certain parameters of the autonomic nervous system and cognitive functions

The objective of the study:to study certain parameters of the autonomic nervous system (ANS) and cognitive functions in patients with acute alcohol intoxication of different severity degrees.Subjects and methods.312 patients with acute alcohol intoxication and chronic alcohol abuse were enrolled in the study. Manifestations, medical history, the duration of drinking bout, ethanol blood level were assessed. Blood panel included ALT, AST, LDH, and blood levels of free ammonia, lactate, and medium molecules. The subjects were divided into three groups: Group I - 78 patients with severe alcohol intoxication, Group II – 166 patients with moderate alcohol intoxication, and Group III – 68 patients with mild alcohol intoxication. The state of ANS was assessed according to the following indicators: heart rate, systolic and diastolic blood pressure, Kerdo vegetative index, and results of cardiointervalography by R.M. Baevsky (1986). The severity of intellectual impairment was assessed using the ММSE scale for 10 positions, the FAB scale for 6 positions, as well as the Reitan test in seconds on the 1st day.Results.In patients of Group I, the alcohol level was 1.5 and 1.35 times lower versus patients in Groups II and III. All patients with severe intoxication had symptoms of toxic hepatitis, which was manifested by a significant increase in ALT, AST, LDH and bilirubin, exceeding the normal limits by 5.4, 5.4, 1.8, and 1.7 times, respectively. Ammonia blood levels in patients with severe intoxication exceeded the norm by 5.6 times, in patients with moderate severity of intoxication – by 3 times, and even in patients with a mild degree – by 1.5 times. The lactic acid level in patients of Group I was 3.2 times above the norm, in patients of Groups II and III – 2.0 and 1.4 times, respectively. In patients with severe intoxication, there was an increase in blood levels of medium molecules over 0.6 units of optical density which reflected severe endogenous intoxication. Assessment of ANS parameters in patients of three groups revealed development of hypersympathicotonia due to the increased tone of the sympathetic department of ANS in proportion to intoxication severity. Cognitive functions at admission were inhibited in proportion to the severity of the patient's condition. Intelligence level as per MMSE scale: at admission, patients of Groups III and II demonstrated mild and moderate cognitive impairment (25.8 ± 2.1 and 23.31 ± 1.80 points); in Group I, indicators for all items were 1.5 times lower versus Groups II and III. Intelligence as per the FAB scale: in patients with severe intoxication, deviations in conceptualization and dynamic praxis were noted. The Reitan test results were best in patients from Group III. Subsequently, 63 (80.7%) patients with severe alcohol intoxication developed alcoholic delirium.Conclusion.Patients with alcohol intoxication demonstrated a decrease in cognitive functions and impaired intelligence proportional to the severity of intoxication and levels of lactate and free ammonia. Increased tone of the sympathetic division of the ANS is typical of acute alcohol intoxication during drinking bout. Cardiointervalography parameters can be used to assess the severity of alcohol intoxication.

Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure.

SummaryLactate shuttled from blood, astrocytes, and/or oligodendrocytes may serve as the major glucose alternative in brain energy metabolism. However, its effectiveness in fueling neuronal information processing underlying complex cortex functions like perception and memory is unclear. We show that sole lactate disturbs electrical gamma and theta-gamma oscillations in hippocampal networks by either attenuation or neural bursts. Bursting is suppressed by elevating the glucose fraction in substrate supply. By contrast, lactate does not affect electrical sharp wave-ripple activity featuring lower energy use. Lactate increases the oxygen consumption during the network states, reflecting enhanced oxidative ATP synthesis in mitochondria. Finally, lactate attenuates synaptic transmission in excitatory pyramidal cells and fast-spiking, inhibitory interneurons by reduced neurotransmitter release from presynaptic terminals, whereas action potential generation in the axon is regular. In conclusion, sole lactate is less effective and potentially harmful during gamma-band rhythms by omitting obligatory ATP delivery through fast glycolysis at the synapse.

Electronic transport properties of nanoribbons of graphene and ψ-graphene -based lactate nanobiosensor

Abstract In this paper, the adsorption of lactate molecules is studied on the two-dimensional structure of graphene and ψ-graphene. First-principle calculations based on density functional theory showed that the absorption energy of the lactate molecule on ψ-graphene is much higher than that of graphene. The monolayer of graphene and ψ-graphene is conductive after the adsorption of lactate molecules. Furthermore, the I-V characteristics based on the non-equilibrium Green's function explain that negative differential resistance occurs in 0.75 V for the absorption of lactate molecules. Based on our findings, AGNR and ZψGNR can be used as the detection of lactate molecule, and ψ-graphene is used as an absorbent of this molecule from the environment.

12. SYNAPTIC DYSFUNCTION IN SCHIZOPHRENIA: EXPLORATION OF NOVEL HYPOTHESES AND PROMISING NEW LEADS

Overall : Accumulating evidence suggests that bioenergetic function is impaired in the brain in schizophrenia. In normal brain, glucose is metabolized to lactate and pyruvate, which are monocarboxylate intermediates that serve as the primary energy source for neurons. Working memory and other cognitive domains are dependent on the shuttling of lactate from astrocytes to neurons. Defects in this complex pathway may underlie cognitive dysfunction in schizophrenia. The focus of this symposium is to present evidence of such defects, and to identify substrates that may be targeted for the development of new treatment strategies. Dr. Laura Rowland (University of Maryland, Baltimore, Maryland, USA) will present evidence of bioenergetic dysfunction in living subjects with schizophrenia. Increased levels of lactate (P < 0.05) were present in the ACC in schizophrenia (n = 27) compared to controls (n = 29). Higher lactate levels were associated with lowers scores on the MATRICS Consensus Cognitive Battery. These data establish a direct link between cognition and bioenergetic function in vivo in schizophrenia. Dr. Robert McCullumsmith (University of Cincinnati, Cincinnati, Ohio, USA) will present evidence of alterations in the lactate shuttle and glycolytic enzymes in postmortem samples from schizophrenia (n = 20) and control subjects (n = 20). Cell-subtype specific changes (P < 0.05) in transcripts include increased levels of the lactate transporter MCT4, decreased levels of the glycolytic enzymes PFK1 and hexokinase, and decreased levels of the glucose transporters Glut1 and Glut3. These data suggest attenuated glycolysis in pyramidal neurons, with a shift towards pathways that boost protection from oxidative stress. The last two speakers will present data that address mechanisms related to these findings, using animal models with behavioral endophenotypes of schizophrenia. Dr. Eduard Bentea (Free University of Brussels (VUB), Brussels, Belgium) will present data from the xCT knockout mouse showing that disruption of system xc-, which supports oxidative stress buffering mechanisms, leads to synaptic dysfunction. Specifically, electron microscopy studies indicate depletion of both pre-and post-synaptic glutamate, while electrophysiological studies show diminished excitatory postsynaptic potentials. These findings directly connect oxidative balance and extracellular glutamate levels with development of “broken” synapses, highlighting a potential mechanism for perturbation of bioenergetic coupling between astrocytes and neurons. Dr. Amy Ramsey (University of Toronto, Toronto, Canada) will present evidence from an animal model of synaptic dysfunction, the GluN1 knockdown mouse. These mice show a bioenergetic defect similar to schizophrenia, with decreased expression of glycolytic enzymes and glucose transporters. These translational findings indicate that genetic risk for schizophrenia may lead to an intermediate bioenergetic phenotype, where diminished supply of lactate and other energetic molecules to neurons could contribute to cognitive dysfunction. Taken together, the work presented by these speakers will provide a fresh look at the bioenergetic defects in schizophrenia, establishing that 1) metabolic perturbations in the brain are prominent and not just an effect antipsychotic treatment, 2) altered neuron-astrocyte coupling leads to synaptic dysfunction, and 3) genetic risk for “broken” synapses disrupts metabolic function.

Live-cell Imaging of Neisseria meningitidis Microcolony Dispersal Induced by Lactate or Other Molecules.

To efficiently colonize the nasopharyngeal epithelium, the human restricted pathogen Neisseria meningitidis follows a multistep adhesion cascade. First, the bacteria adhere to host cells and aggregate into spherical shaped structures called microcolonies. Several hours later, single bacteria start dispersing from the microcolonies and form a monolayer on top of the host cells. Once in proximity to host cells meningococci can adhere tightly to the epithelial surface or become internalized. This can eventually result in invasion of the mucosal surfaces and gain access to the bloodstream, causing a life-threatening disease. Lactate, a metabolite derived from human epithelial cells, has been previously shown to induce rapid dispersal of N. meningitidis from microcolonies. Here, we describe a host-cell free method based on live-cell imaging to examine the effect of host derived lactate on the timing of N. meningitides microcolony dispersal. Although in this protocol we use lactate, it can be easily modified to test the effects of other molecules.

Modeling glucose metabolism and lactate production in the kidney

The metabolism of glucose provides most of the ATP required for energy-dependent transport processes. In the inner medulla of the mammalian kidney, limited blood flow and O2 supply yield low oxygen tension; therefore, a substantial fraction of the glucose metabolism in that region is anaerobic. Lactate is considered to be a waste product of anaerobic glycolysis, which yields two lactate molecules for each glucose molecule consumed, thereby likely leading to the production and accumulation of a significant amount of lactate in the inner medulla. To gain insights into the transport and metabolic processes in the kidney, we have developed a detailed mathematical model of the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension and glucose and lactate concentrations in the outer medulla and upper inner medulla. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. Using this model, we have identified parameters concerning glucose transport and basal metabolism, as well as lactate production via anaerobic glycolysis, that yield predicted blood glucose and lactate concentrations consistent with experimental measurements in the papillary tip. In addition, simulations indicate that the radial organization of the rat kidney may affect lactate buildup in the inner medulla.

Permeability and diffusion coefficients of single methyl lactate enantiomers in Nafion® and cellophane membranes measured in diffusion cell

A two-compartment horizontal diffusion cell of own construction was used to measure the permeability and diffusion coefficients for the test system toluene in low density polyethylene (LDPE) and for chiral d- and l-methyl lactates in Nafion® and cellophane. The solvent was chosen such that it was not absorbed in the membrane. The evaluation process was developed to include the accumulation of the solute in the membrane or the change in the membrane thickness. There is a significant difference between the transport and sorption of methyl lactates in Nafion® and cellophane, respectively. The methyl lactate enantiomers show a comparable relative difference (50% approximately) in the case of the mass sorption and permeability coefficient values in Nafion® and therefore very similar values of diffusion coefficients, but a tenfold higher permeability coefficient of one enantiomer in comparison with the second one in cellophane while sorption coefficient is, again, different by 50% approximately in this case resulting in fifteenfold higher diffusion coefficient of one enantiomer. Furthermore, there is an opposite difference between the mass sorption and swelling of the membrane in the case of methyl lactate enantiomers in Nafion®: d-methyl lactate shows a higher mass sorption but lower areal swelling compared with the results of l-methyl lactate in Nafion® in the case of dilute solutions. A possible explanation for this fact is that d-methyl lactate fits like a puzzle piece into Nafion’s secondary or primary structure and that l-methyl lactate molecules cause more extensive stretching of polymer backbones due to specific force actions. Despite of the observed chiral membrane properties, chiral resolution of racemic mixture of methyl lactates was not reached.

Insights into alkyl lactate + water mixed fluids

The properties and nanoscopic structure of alkyl lactate+water binary mixtures were studied at 298.15K in the whole composition range. Thermophysical measurements and spectroscopic studies allowed analysing the characteristics of intermolecular forces, hydrogen bonding, together with structural effects upon mixing as a function of mixture composition. The role developed by the bifunctional character of alkyl lactate molecules on the development of homo and heteroassociations is studied and its effect on the relationship between macro and microscopic fluid properties.

Endurance training alters skeletal muscle MCT contents in T2DM men.

Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.

Hydrogen bonding in homochiral dimers of hydroxyesters studied by Raman optical activity spectroscopy

Spectroscopic analysis of homochiral dimerization is important for the understanding of the homochirality of life and enantioselective catalysis. In this paper, (S)‐methyl lactate and related molecules were studied to provide detailed structural information on hydrogen bonding in homochiral dimers of chiral α‐hydroxyesters through the experimental and theoretical study of Raman optical activity. Different homochiral dimers can be distinguished by comparing their simulated Raman optical activity spectra with the experimental results. Hydrogen bonding motions are decoded with the aid of vibrational motion analysis, which are apparently involved in vibrational motions below 800 cm–1. A common feature related to the chain‐bending mode also indicates the absolute configuration of methyl lactate and related molecules. The differing behavior of electric dipole–electric quadrupole invariants (β(A)2) compared with the electric dipole–magnetic dipole invariant (β(G′)2), suggests that the intermolecular hydrogen bonding motion behaves differently from the intramolecular one in the asymmetric molecular electric and magnetic fields. These results may help understand hydrogen‐bonded self‐recognition and other dynamical features in chiral recognition. Copyright © 2011 John Wiley &amp; Sons, Ltd.