Fundamental Biomolecules Research Articles

Nanopore-based glycan sequencing: state of the art and future prospects.

Sequencing of biomacromolecules is a crucial cornerstone in life sciences. Glycans, one of the fundamental biomolecules, derive their physiological and pathological functions from their structures. Glycan sequencing faces challenges due to its structural complexity and current detection technology limitations. As a highly sensitive sensor, nanopores can directly convert nucleic acid sequence information into electrical signals, spearheading the revolution of third-generation nucleic acid sequencing technologies. However, their potential for deciphering complex glycans remains untapped. Initial attempts demonstrated the significant sensitivity of nanopores in glycan sensing, which provided the theoretical basis and insights for the realization of nanopore-based glycan sequencing. Here, we present three potential technical routes to employ nanopore technology in glycan sequencing for the first time. The three novel technical routes include: strand sequencing, capturing glycan chains as they translocate through nanopores; sequential hydrolysis sequencing, capturing released monosaccharides one by one; splicing sequencing, mapping signals from hydrolyzed glycan fragments to an oligosaccharide database/library. Designing suitable nanopores, enzymes, and motors, and extracting characteristic signals pose major challenges, potentially aided by artificial intelligence. It would be highly desirable to design an all-in-one high-throughput glycan sequencer instrument by integrating a sample processing unit, nanopore array, and signal acquisition system into a microfluidic device. The nanopore sequencer invention calls for intensive multidisciplinary cooperation including electrochemistry, glycochemistry, engineering, materials, enzymology, etc. Advancing glycan sequencing will promote the development of basic research and facilitate the discovery of glycan-based drugs and disease markers, fostering progress in glycoscience and even life sciences.

Ecological fabrication of copper oxide nanoparticles for enhanced photocatalytic degradation of methylene blue and rhodamine B. Dye

Industrial wastewater has been an alarming issue that can have harmful effects on humans and the environment. Numerous treatment methods have been introduced to reduce toxicity, but photocatalyst treatment has been gaining interest because of its environmental behavior. This study used Grewia asiatica L. extract, which was not previously utilized to synthesize the copper oxide nanoparticles; various spectroscopic and microscopic techniques were used to characterizesynthesized nanoparticles. The UV–visible spectrophotometer spectra showed an absorbance peak at 248 nm that confirmed the synthesis of copper oxide nanoparticles. Similarly, the scanning electron microscope (SEM) and X-ray Diffraction (XRD) revealed that the synthesized nanoparticles have a size of 33.71 nm and are spherical. The energy dispersive x-ray (EDX) spectra showed the sample's elemental composition, in which copper and oxygen are present in high percentages. The Fourier infrared spectrophotometer (FTIR) spectra confirmed the fundamental biomolecules that have reduced and stabilized the copper oxide nanoparticles. The synthesized nanoparticles were developed as a catalyst under solar radiation to reduce methylene blue and rhodamine B dyes. Methylene blue was degraded 92% in 25 min with a 0.0397 min−1 rate constant. The Rhodamine B dye was degraded 98% in 50 min with a rate constant of 0.0198 min−1. Results revealed that Grewia asiatica L. mediated copper oxide nanoparticles can be used as a wastewater treatment catalystto reduce toxic dyes.

Advancing Glycan Analysis: A New Platform Integrating SERS, Boronic Acids, and Machine Learning Algorithms

AbstractGlycans are the most abundant fundamental biomolecules, but profiling glycans is challenging due to their structural complexity. To address this, a novel glycan detection platform is developed by integrating surface‐enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. Boronic acid receptors bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. Unlike prior studies that focus on designing a boronic acid with high binding selectivity toward a target glycan, this sensor is designed to analyze overall changes in spectral patterns using machine learning algorithms. For proof‐of‐concept, 4‐mercaptophenylboronic acid (4MBA) and 1‐thianthrenylboronic acid (1TBA) are used for glycan detection. The sensing platform successfully recognizes the stereoisomers and the structural isomers with different glycosidic linkages. The collective spectra that combine the spectra from both boronic acid receptors improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. This low‐cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent comparative glycan screening in standard biological laboratories.

Correlation of Lipid Profile with Inflammatory Markers among COVID-19 Positive Patients: A Retrospective Study

Introduction: Lipids are fundamental biomolecules of the body. Infections like COVID-19 with intricate immune response in some patient’s leads to acute complications by affecting metabolic pathways at multiple levels. Metabolism of cholesterol, triglyceride and High Density Lipoprotein (HDL)-Cholesterol is deranged by cytokines and multiple inflammatory mediators. The sex differences in lipid metabolism may contribute in susceptibility, severity and outcome of Coronavirus Disease 2019 (COVID-19). Performing lipid profile in COVID-19 patient may help in assessing severity and prognosis of disease. Aim: To assess the relationship between lipid profile and inflammatory markers in COVID-19 patients and also to evaluate the gender wise differences in lipid parameters and their correlations with inflammatory markers. Materials and Methods: This retrospective study was conducted in Department of Biochemistry at SHKM, GMC, Mewat, Haryana, India (tertiary care health centre) on COVID-19 positive patients attending Outpatient Department (OPD) and Inpatient Department (IPD), from October 2020 to December 2020. The data of 85 patients with COVID-19 positive, confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and who were prescribed for lipid profile along with C-Reactive Protein (CRP) and serum ferritin were included in the study. Serum total cholesterol, triglyceride, HDL-Cholesterol, CRP and ferritin were measured in the subjects. Data was statistically analysed using Student’s t test and Pearson correlation coefficient. Results: Total 85 (46 males and 39 females) COVID-19 patients were included in the study. Mean age in male and female patients were 43.02±15.52 years and 42.02±15.25 years, respectively with a range of 5-82 years. Mean value of Serum triglycerides, HDL-C and total cholesterol was 204.94±141.27 mg/dL, 42.97±13.38 mg/ dL and 187.058±45.75 mg/dL, respectively. Serum triglycerides were statistically significantly higher in males than females (pvalue=0.0413). The HDL-C however was significantly higher in females than males (p-value=0.0006). In male patients, r-value between cholesterol and CRP was -0.3538, and p-value was 0.016. Ferritin had a significant negative correlation with HDL-C (r-value=-0.3578, p-value=0.00079). Weak Positive correlation was noted between triglyceride and ferritin (r-value= 0.2285, p-value=0.035). Conclusion: High levels of serum triglycerides, low total cholesterol, and low HDL-cholesterol correlates with inflammatory markers like CRP and ferritin in COVID-19 patients. Lipid profile may be used as a potential marker in all COVID-19 patients in assessing prognosis of disease.

Strategies for Post-Translational Control of Protein Expression and Their Applications

Proteins are fundamental biomolecules of living cells, and their expression levels depend on the balance between the synthesis and degradation. Researchers often aim to control protein expression levels for the investigation of protein function and its relationship with physiological phenomena. The genetic manipulation of the target protein using CRISPR/Cas9, Cre/loxP, tetracyclin system, and RNA interference, are widely used for the regulation of proteins at the DNA, transcriptional, or mRNA level. However, the significant time delay in controlling protein levels is a limitation of these techniques; the knockout or knockdown effects cannot be observed until the previously transcribed and synthesized protein is degraded. Recently, researchers have developed various types of molecular tools for the regulation of protein expression at the post-translational level, which rely on harnessing cellular proteolytic machinery including ubiquitin–proteasome pathway, autophagy-lysosome pathway, and endocytosis. The post-translational control of protein expression using small molecules, antibodies, and light can offer significant advantages regarding speed, tunability, and reversibility. These technologies are expected to be applied to pharmacotherapy and cell therapy, as well as research tools for fundamental biological studies. Here, we review the established and recently developed technologies, provide an update on their applications, and anticipate potential future directions.

Brief Note on Glycans and Synthesis of Bacterial Glycans

Glycans are fundamental biomolecules in managing human physiology and pathology going from signal transduction to microbial diseases. Creating complex human illnesses, like malignancy, diabetes, and cardiovascular sicknesses, are a blend of hereditary and natural variables. Hereditary qualities overcome early stage improvement and the death of qualities to the future while the data in glycans mirrors the effect of inner and outside ecological components, like illnesses, way of life, and social variables, on an individual's wellbeing and sickness.

Nanoscale oligopeptide adsorption behaviour on chlorite as revealed by scanning probe microscopy and density functional simulations

In the present work, the interaction between simple oligopeptides of L-alanine (di-L-alanine) and the (001) surface of clinochlore was characterized in details by employing cross-correlated atomic force microscopy (AFM) observations and Density Functional Theory (DFT) simulations. The AFM results showed that the mineral surface is able to stably bind L-alanine peptides preferentially onto the brucite-like sheets of clinochlore during an interaction in a water suspension. In particular, the (001) surface acted as a condensing and agglomerating system, where AFM evidenced di-L-alanine oligopeptides organized in dot-like, agglomerates and filament-like structures up to more than 160 nm in length, in the experimental conditions here used. DFT simulations were conducted to analyse at the atomic scale the interaction between di-L-alanine oligopeptides and the mineral, finding the molecular conformation with the lowest energy, the adsorption (binding) energy between the oligopeptide and the brucitic surface and also the hydrogen bonding scheme. The reported findings constitute a further step towards the comprehension of the interaction mechanisms between fundamental biomolecules and clay mineral surfaces, of paramount importance for environmental sequestration and biotechnological purposes, but also for prebiotic chemistry research.

Global Nitrogen Cycle: Critical Enzymes, Organisms, and Processes for Nitrogen Budgets and Dynamics.

Nitrogen (N) is used in many of life's fundamental biomolecules, and it is also a participant in environmental redox chemistry. Biogeochemical processes control the amount and form of N available to organisms ("fixed" N). These interacting processes result in N acting as the proximate limiting nutrient in most surface environments. Here, we review the global biogeochemical cycle of N and its anthropogenic perturbation. We introduce important reservoirs and processes affecting N in the environment, focusing on the ocean, in which N cycling is more generalizable than in terrestrial systems, which are more heterogeneous. Particular attention is given to processes that create and destroy fixed N because these comprise the fixed N input/output budget, the most universal control on environmental N availability. We discuss preindustrial N budgets for terrestrial and marine systems and their modern-day alteration by N inputs from human activities. We summarize evidence indicating that the simultaneous roles of N as a required biomass constituent and an environmental redox intermediate lead to stabilizing feedbacks that tend to blunt the impact of N cycle perturbations at larger spatiotemporal scales, particularly in marine systems. As a result of these feedbacks, the anthropogenic "N problem" is distinct from the "carbon dioxide problem" in being more local and less global, more immediate and less persistent.

Impact of UV Radiation on Genome Stability and Human Health.

Gradual depletion of the atmospheric ozone layer during the past few years has increased the incidence of solar UV radiation specifically the UV-C on earth's surface is one of the major environmental concerns because of the harmful effects of this radiation in all forms of life. The solar UV radiation including the harmful wavelength range of UV-B (280-320nm) represents a significant climatic stress for both animals and plants, causing damage to the fundamental biomolecules such as DNA, proteins and lipids, thus activating genotoxic stress and induces genome instability. When DNA absorbs UV-B light, energy from the photon causes covalent linkages to form between adjacent pyrimidine bases, creating photoproducts, primarily cyclobutane pyrimidine dimers (CPDs) and pyrimidine-6,4-pyrimidinone photoproduct (6,4PPs). Pyrimidine dimers create distortions in the DNA strands and therefore can inhibit DNA replication as well transcription. Lack of efficient repair of UV-induced DNA damage may induce the formation of DNA double stand breaks (DSBs), one of the serious forms of damage in DNA double helix, as well as oxidative damage. Unrepaired DSBs in the actively dividing somatic cells severely affect cell growth and development, finally results in loss of cell viability and development of various diseases, such as cancer in man.This chapter mainly highlights the incidence of solar UV-radiation on earth's surface along with the formation of major types of UV-induced DNA damage and the associated repair mechanisms as well as methods of detecting DNA damage and finally our present understanding on the impact on solar UV radiation on human health.

Nitrogen cycling in the deep sedimentary biosphere: nitrate isotopes in porewaters underlying the oligotrophic North Atlantic

Abstract. Nitrogen (N) is a key component of fundamental biomolecules. Hence, its cycling and availability are central factors governing the extent of ecosystems across the Earth. In the organic-lean sediment porewaters underlying the oligotrophic ocean, where low levels of microbial activity persist despite limited organic matter delivery from overlying water, the extent and modes of nitrogen transformations have not been widely investigated. Here we use the N and oxygen (O) isotopic composition of porewater nitrate (NO3−) from a site in the oligotrophic North Atlantic (Integrated Ocean Drilling Program – IODP) to determine the extent and magnitude of microbial nitrate production (via nitrification) and consumption (via denitrification). We find that NO3- accumulates far above bottom seawater concentrations (~ 21 μM) throughout the sediment column (up to ~ 50 μM) down to the oceanic basement as deep as 90 m b.s.f. (below sea floor), reflecting the predominance of aerobic nitrification/remineralization within the deep marine sediments. Large changes in the δ15N and δ18O of nitrate, however, reveal variable influence of nitrate respiration across the three sites. We use an inverse porewater diffusion–reaction model, constrained by the N and O isotope systematics of nitrification and denitrification and the porewater NO3- isotopic composition, to estimate rates of nitrification and denitrification throughout the sediment column. Results indicate variability of reaction rates across and within the three boreholes that are generally consistent with the differential distribution of dissolved oxygen at this site, though not necessarily with the canonical view of how redox thresholds separate nitrate regeneration from dissimilative consumption spatially. That is, we provide stable isotopic evidence for expanded zones of co-occurring nitrification and denitrification. The isotope biogeochemical modeling also yielded estimates for the δ15N and δ18O of newly produced nitrate (δ15NNTR (NTR, referring to nitrification) and δ18ONTR), as well as the isotope effect for denitrification (15ϵDNF) (DNF, referring to denitrification), parameters with high relevance to global ocean models of N cycling. Estimated values of δ15NNTR were generally lower than previously reported δ15N values for sinking particulate organic nitrogen in this region. We suggest that these values may be, in part, related to sedimentary N2 fixation and remineralization of the newly fixed organic N. Values of δ18ONTR generally ranged between −2.8 and 0.0 ‰, consistent with recent estimates based on lab cultures of nitrifying bacteria. Notably, some δ18ONTR values were elevated, suggesting incorporation of 18O-enriched dissolved oxygen during nitrification, and possibly indicating a tight coupling of NH4+ and NO2− oxidation in this metabolically sluggish environment. Our findings indicate that the production of organic matter by in situ autotrophy (e.g., nitrification, nitrogen fixation) supplies a large fraction of the biomass and organic substrate for heterotrophy in these sediments, supplementing the small organic-matter pool derived from the overlying euphotic zone. This work sheds new light on an active nitrogen cycle operating, despite exceedingly low carbon inputs, in the deep sedimentary biosphere.

A multi-omic analysis of human naïve CD4+ T cells.

BackgroundCellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases. Nevertheless, a unified analysis of the genome, epigenome, transcriptome and proteome of a single human cell type to obtain a coherent view of the complex interplay between various biomolecules has not yet been undertaken. Here, we report the first multi-omic analysis of human primary naïve CD4+ T cells isolated from a single individual.ResultsIntegrating multi-omics datasets allowed us to investigate genome-wide methylation and its effect on mRNA/protein expression patterns, extent of RNA editing under normal physiological conditions and allele specific expression in naïve CD4+ T cells. In addition, we carried out a multi-omic comparative analysis of naïve with primary resting memory CD4+ T cells to identify molecular changes underlying T cell differentiation. This analysis provided mechanistic insights into how several molecules involved in T cell receptor signaling are regulated at the DNA, RNA and protein levels. Phosphoproteomics revealed downstream signaling events that regulate these two cellular states. Availability of multi-omics data from an identical genetic background also allowed us to employ novel proteogenomics approaches to identify individual-specific variants and putative novel protein coding regions in the human genome.ConclusionsWe utilized multiple high-throughput technologies to derive a comprehensive profile of two primary human cell types, naïve CD4+ T cells and memory CD4+ T cells, from a single donor. Through vertical as well as horizontal integration of whole genome sequencing, methylation arrays, RNA-Seq, miRNA-Seq, proteomics, and phosphoproteomics, we derived an integrated and comparative map of these two closely related immune cells and identified potential molecular effectors of immune cell differentiation following antigen encounter.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0225-4) contains supplementary material, which is available to authorized users.

Nucleotides, RNA and DNA selective adsorption on atomic-flat Mg–Al-hydroxysilicate substrates

The search and characterisation of new nanomaterials and their application to nanomanipulate biomolecules are modern challenges of nanoscience and nanotechnology. Both synthetic and natural materials are widely investigated. In this Letter the authors report on the interaction of fundamental biomolecules with atomic-flat natural magnesium–aluminium-hydroxysilicate substrates. The surface affinity, self-assembly and nanopatterning of nucleotides, RNA and DNA, are compared. All biomolecules selectively adsorb on the surface of the magnesium hydroxide layer. Nucleotides are lined-up at the edges of magnesium hydroxide in long filamentary structures. RNA molecules are observed as agglomerates, globular domains separated by strands, and also in stable linearised structures. DNA can be bridged between two magnesium hydroxide layers in a stretched conformation longer than 2 µm (>6000 bp).

Comment on “A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus”

Wolfe-Simon et al. (Research Articles, 3 June 2011, p. 1163; published online 2 December 2010) reported the discovery of an unusual bacterium, strain GFAJ-1, that can grow in the presence of high concentrations of arsenate. The authors' contention, however, that this microbe can appreciably vary the elemental composition of its fundamental biomolecules by substituting arsenic for phosphorus appears premature based on the data presented.

Peroxisomal Plant 3-Ketoacyl-CoA Thiolase Structure and Activity Are Regulated by a Sensitive Redox Switch

The breakdown of fatty acids, performed by the beta-oxidation cycle, is crucial for plant germination and sustainability. beta-Oxidation involves four enzymatic reactions. The final step, in which a two-carbon unit is cleaved from the fatty acid, is performed by a 3-ketoacyl-CoA thiolase (KAT). The shortened fatty acid may then pass through the cycle again (until reaching acetoacetyl-CoA) or be directed to a different cellular function. Crystal structures of KAT from Arabidopsis thaliana and Helianthus annuus have been solved to 1.5 and 1.8 A resolution, respectively. Their dimeric structures are very similar and exhibit a typical thiolase-like fold; dimer formation and active site conformation appear in an open, active, reduced state. Using an interdisciplinary approach, we confirmed the potential of plant KATs to be regulated by the redox environment in the peroxisome within a physiological range. In addition, co-immunoprecipitation studies suggest an interaction between KAT and the multifunctional protein that is responsible for the preceding two steps in beta-oxidation, which would allow a route for substrate channeling. We suggest a model for this complex based on the bacterial system.

Parameterization of a dynamic specific activity model of 14C transfer from surface water-to-humans

Carbon-14 is a particularly interesting radionuclide from the perspective of dose estimation because it mixes readily with stable CO 2, and hence enters the food-chain as fundamental biomolecules. A model was developed for the situation of 14C releases to surface waters, where there are distinct changes in the water 14C activity concentrations throughout the year. The model computes the specific activity in water, phytoplankton, fish, crops, meat, milk and air, following a typical irrigation-based food-chain scenario. This paper describes the derivation of the required 14C-specific parameter values. Many of the key parameters are not commonly measured, at least not in the context of dose assessment. Thus, inference from other sources of data was required, and this is the scientific contribution described in this paper. The best estimates and appropriate measures of statistical dispersion are provided. This required consideration of both the temporal and spatial averaging domains to ensure they were correct for parameters as defined in the model. The model coupled with these parameter values represents several new developments for modelling 14C transfers.

Conceptual approaches for the development of dynamic specific activity models of 14C transfer from surface water to humans

Carbon-14 is a particularly interesting radionuclide from the perspective of dose estimation. Many nuclear facilities, including power reactors, release 14C into the environment, and much of this is as 14CO 2. This mixes readily with stable CO 2, and hence enters the food chain as fundamental biomolecules. This isotopic mixing is often used as the basis for dose assessment models. The present model was developed for the situation of 14C releases to surface waters, where there are distinct changes in the water 14C activity concentrations throughout the year. Complete isotopic mixing (equilibrium) cannot be assumed. The model computes the specific activity (activity of 14C per mass of total C) in water, phytoplankton, fish, crops, meat, milk and air, following a typical irrigation-based food-chain scenario. For most of the biotic compartments, the specific activity is a function of the specific activity in the previous time step, the specific activity of the substrate media, and the C turnover rate in the tissue. The turnover rate is taken to include biochemical turnover, growth dilution and mortality, recognizing that it is turnover of C in the population, not a tissue or an individual, that is relevant. Attention is paid to the incorporation of 14C into the surface water biota and the loss of any remaining 14CO 2 from the surface water–air interface under its own activity concentration gradient. For certain pathways, variants in the conceptual model are presented, in order to fully discuss the possibilities. As an example, a new model of the soil-to-plant specific activity relationship is proposed, where the degassing of both 14C and stable C from the soil is considered. Selection of parameter values to represent the turnover rates as modeled is important, and is dealt with in a companion paper.

Are the conformational dynamics and the ligand binding properties of myoglobin affected by exposure to microwave radiation?

The global uptake of mobile communication emphasizes the question about possible adverse consequences of the exposure to low-level radiofrequency radiation from mobile phones on human health as result of so-called "non-thermal effects". In order to state safety guidelines it seems appropriate to start by excluding, if possible, non-specific effects on structural and dynamic properties of fundamental biomolecules such as proteins. Proteins are flexible polyelectrolytes; thus, they are susceptible, in principle, to the action of electromagnetic fields. In this article, we investigated the effects of microwaves on structural and functional properties of Tunnus tynnus myoglobin at 1.95 GHz, a frequency used by new wireless microwave communication systems. The protein solution was exposed for 2.5 h to 51 mW/g SAR (specific absorption rate) level. Measurements of absorption spectroscopy, circular dichroism and fluorescence emission decay in the frequency domain do not exhibit any influence of the radiation on the native structural state of protein macromolecules.

Bridging the gap between physiology and molecular biology: new approaches to perpetual questions

Living organisms are the result of precise and complex associations of regulatory systems in which active biomolecules interact with one another and respond to the challenges of growth and development, alterations in the environment, and disease. Understanding of body homeostasis may be accomplished at various levels of scientific endeavor. Physiological research has brought about an enormous understanding of the fundamental principles that sustain life in health and disease. The field of molecular biology has provided new tools and strategies with which to examine physiological processes as viewed from the level of fundamental biomolecules. The integration of both fields as "molecular physiology" has provided the opportunity for another level of scientific understanding and the opening of new avenues of research. Renin is one such molecule that participates in the control of several diverse physiological responses including changes in blood pressure, fluid and electrolyte homeostasis, renal function, and perhaps some elements of growth and differentiation. Because of the authors' bias, this review article will use renin to introduce many of the techniques of molecular biology and illustrate the areas of ongoing and potential interdependent activities resulting in the emerging field of molecular physiology.

Parity violation and the origins of biomolecular handedness

The violation of parity by the weak interactions ensures that enantiomeric chiral molecules have inequivalent energies, one being inherently stabilized with respect to the other. These parity-violating energy differences have been calculated for a number of fundamental biomolecules including a series of a-amino acids, polypeptide structures, and a representative of the sugar series together with its variation over a possible prebiotic reaction path leading to α-amino acids. In each case the natural enantiomer found in terrestrial biochemistry was shown to be intrinsically stabilized and preferred over its unnatural enantiomer. The significance of these results in accounting for the prebiotic origins of the terrestrial biomolecular homochirality is discussed and the possible consequences of parity-violating energy differences in mineral catalysts during the prebiotic era considered.

The parity violating energy differences between the enantiomers of α-amino acids

The parity-violating weak neutral current perturbation of the groundstate electronic energy has been calculated, using ab initio methods, for the series of α-amino acids glycine, alanine, valine, serine and aspartic acid. It is found that the WNC energy shifts for these fundamental biomolecules consistently favour the existence of the natural L-enantiomers in preference to the unnatural mirror image D-enantiomers for the molecular conformations preferred in aqueous media. The parity violating energy differences between enantiomers are small, of the order 10-14 J mol-1, and highly sensitive to molecular conformation. The significance of the energy difference between enantionmers arising from the electroweak interactions with reference to the transition from a prebiotic racemic geochemistry to the terrestrial homochiral biochemistry is discussed.