Enteric coronavirus PDCoV evokes a non-Warburg effect by hijacking pyruvic acid as a metabolic hub.

The Warburg effect, also referred as aerobic glycolysis, is a common metabolic program during viral infection. Through targeted metabolomics combined with biochemical experiments and various cell models, we investigated the central carbon metabolism (CCM) profiles of cells infected with porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus with zoonotic potential. We found that PDCoV infection required glycolysis but decreased glycolytic flux, exhibiting a non-Warburg effect characterized by pyruvic acid accumulation. Mechanistically, PDCoV enhanced pyruvate kinase activity to promote pyruvic acid anabolism, a process that generates pyruvic acid with concomitant ATP production. PDCoV also hijacked pyruvic acid catabolism to increase biosynthesis of non-essential amino acids (NEAAs), suggesting that pyruvic acid is an essential hub for PDCoV to scavenge host energy and metabolites. Furthermore, PDCoV facilitated glutaminolysis to promote the synthesis of NEAA and pyrimidines for optimal proliferation. Our work supports a novel CCM model after viral infection and provides potential anti-PDCoV drug targets.

Tanshinone analog inhibits castration-resistant prostate cancer cell growth by inhibiting glycolysis in an AR-dependent manner.

Androgen receptor (AR) is one of the key targets for the treatment of castration-resistant prostate cancer (CRPC). Current endocrine therapy can greatly improve patients with CRPC. However, with the change of pathogenic mechanism, acquired resistance often leads to the failure of treatment. Studies have shown that tanshinone IIA (TS-IIA) and its derivatives have significant antitumor activity, and have certain AR-targeting effects, but the mechanism is unknown. In this study, the TS-IIA analog TB3 was found to significantly inhibit the growth of CRPC in vitro and in vivo. Molecular docking, cellular thermal shift assay, and cycloheximide experiments confirmed that AR was the target of TB3 and promoted the degradation of AR. Furthermore, TB3 can significantly inhibit glycolysis metabolism by targeting the AR/PKM2 axis. The addition of pyruvic acid could significantly alleviate the inhibitory effect of TB3 on CRPC cells. Besides, the knockdown of AR or PKM2 also could reverse the effect of TB3 on CRPC cells. Taken together, our study suggests that TS-IIA derivative TB3 inhibits glycolysis to prevent the CRPC process by targeting the AR/PKM2 axis.

Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB).

BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.

Simultaneous Analysis of Organic Acids, Glycerol and Phenolic Acids in Wines Using Gas Chromatography-Mass Spectrometry.

Fermented beverages, particularly wines, exhibit variable concentrations of organic and phenolic acids, posing challenges in their accurate determination. Traditionally, enzymatic methods or chromatographic analyses, mainly high-performance liquid chromatography (HPLC), have been employed to quantify these compounds individually in the grape must or wine. However, chromatographic analyses face limitations due to the high sugar content in the grape must. Meanwhile, phenolic acids, found in higher quantities in red wines than in white wines, are typically analyzed using HPLC. This study presents a novel method for the quantification of organic acids (OAs), glycerol, and phenolic acids in grape musts and wines. The approach involves liquid-liquid extraction with ethyl acetate, followed by sample derivatization and analysis using gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) detection mode. The results indicated successful detection and quantification of all analyzed compounds without the need for sample dilution. However, our results showed that the method of adding external standards was more suitable for quantifying wine compounds, owing to the matrix effect. Furthermore, this method is promising for quantifying other metabolites present in wines, depending on their extractability with ethyl acetate. Fermented beverages, particularly wines, exhibit variable concentrations of organic and phenolic acids, posing challenges in their accurate determination. Traditionally, enzymatic methods or chromatographic analyses, mainly high-performance liquid chromatography (HPLC), have been employed to quantify these compounds individually in the grape must or wine. The approach of this proposed method involves (i) methoximation of wine compounds in a basic medium, (ii) acidification with HCl, (iii) liquid-liquid extraction with ethyl acetate, and (iv) silyl derivatization to analyze samples with gas chromatography-mass spectrometry (GC-MS) in ion monitoring detection mode (SIM). The results indicated successful detection and quantification of all analyzed compounds without the need for sample dilution. However, our results showed that the method of adding external standards was more suitable for quantifying wine compounds, owing to the matrix effect. Furthermore, this method is promising for quantifying other metabolites present in wines, depending on their extractability with ethyl acetate. In other words, the proposed method may be suitable for profiling (targeted) or fingerprinting (untargeted) strategies to quantify wine metabolites or to classify wines according to the type of winemaking process, grape, or fermentation.

Comparison of Selenic Acid and Pyruvic Acid-Loaded Silver Nanocarriers Impact on Colorectal Cancer Viability.

Colorectal cancer (CRC) is a leading cause of morbidity and death worldwide. As current cancer drugs are ineffective, new solutions are being sought in other fields, including nanoscience. Similarly, silver nanoparticles play an important role in the pharmaceutical industry as they act as anti-cancer agents with less harmful effects and are usually 1 to 100 nm in size. Selenic acid (SA) and pyruvic acid (PA) are involved in various metabolic pathways in cancer. For this reason, we decided to detect their influence on colorectal cancer using silver-based (Ag) nanocarriers. DLS, Zetasizer, SEM and UV-Vis analyses were used to characterize AgSA and AgPA. A UV spectrophotometer was used to analyze the release of the NPs. MTT analyses were used to measure the viability of HCT116 and HUVEC cells, and IC50 values were calculated using GraphPad Prism. The indicated dosage and particle size of AgSA NPs proved to be suitable for cytotoxicity. Moreover, injection of these nanoparticles into non-cancer cells proved safe due to their minimal toxicity. In contrast, the AgPA NPs have no cytotoxicity and induce proliferation of HCT116 cells. Finally, only the synthesised AgSA nanoparticles could be used for advanced cancer therapy, which is both inexpensive and has minimal side effects.

Simultaneous achievement of efficient hemicellulose separation and inhibition of lignin repolymerization using pyruvic acid treatment.

The efficiency of organic acid treatment in the conversion of lignocellulosic biomass fractions has been widely recognized. In this study, a novel green pyruvic acid (PA) treatment is proposed. The higher separation efficiency of eucalyptus hemicellulose was obtained at 4.0% PA and 150 °C. The hemicellulose separation yield was increased from 71.71 to 88.09% compared to glycolic acid (GA) treatment. In addition, the treatment time was significantly reduced from 180 to 40 min. The proportion of cellulose in the solid increased after PA treatment. However, the accompanying separation of lignin was not effectively controlled. Fortunately, a six-membered ring structure was formed on the diol structure of the lignin ß-O-4 side chain. Fewer lignin-condensed structures were observed. High-value lignin rich in phenol hydroxyl groups were obtained. It provides a green path for the simultaneous achievement of efficient hemicellulose separation and inhibition of lignin repolymerization using organic acid treatment.

Co-production of 7-chloro-tryptophan and indole pyruvic acid based on an efficient FAD/FADH2 regeneration system.

Efficient FAD/FADH2 regeneration is vital for enzymatic biocatalysis and metabolic pathway optimization. Here, we constructed an efficient and simple FAD/FADH2 regeneration system through a combination of L-amino acid deaminase (L-AAD) and halogenase (CombiAADHa), which was applied for catalyzing the conversion of an L-amino acid to halide and an α-keto acid. For cell-free biotransformation, the optimal activity ratio of L-AAD and halogenase was set between 1:50 and 1:60. Within 6 h, 170 mg/L of 7-chloro-tryptophan (7-Cl-Trp) and 193 mg/L of indole pyruvic acid (IPA) were synthesized in the selected mono-amino acid system. For whole-cell biotransformation, 7-Cl-Trp and IPA synthesis was enhanced by 15% (from 96 to 110 mg/L) and 12% (from 115 to 129 mg/L), respectively, through expression fine-tuning and the strengthening of FAD/FADH2 supply. Finally, ultrasound treatment was applied to improve membrane permeability and adjust the activity ratio, resulting in 1.6-and 1.4-fold higher 7-Cl-Trp and IPA yields. The products were then purified. This system could also be applied to the synthesis of other halides and α-keto acids. KEY POINTS: • In this study, a whole cell FAD/FADH2 regeneration system co-expressing l-AAD and halogenase was constructed • This study found that the activity and ratio of enzyme and the concentration of cofactors had a significant effect on the catalytic process for the efficient co-production of 7-chlorotryptophan and indole pyruvate.

Activation of the aryl hydrocarbon receptor inhibits the development of experimental autoimmune pancreatitis through IL-22-mediated signaling pathways.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in hematopoietic and non-hematopoietic cells. Activation of the AhR by xenobiotics, microbial metabolites, and natural substances induces immunoregulatory responses. Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disorder of the pancreas driven by autoimmunity. Although AhR activation generally suppresses pathogenic autoimmune responses, the roles played by the AhR in AIP have been poorly defined. In this study, we examined how AhR activation affected the development of experimental AIP caused by the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Experimental AIP was induced in MRL/MpJ mice by repeated injections of polyinosinic-polycytidylic acid. Activation of the AhR by indole-3-pyruvic acid and indigo naturalis, which were supplemented in the diet, inhibited the development of experimental AIP, and these effects were independent of the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Interaction of indole-3-pyruvic acid and indigo naturalis with AhRs robustly augmented the production of IL-22 by pancreatic islet α cells. The blockade of IL-22 signaling pathways completely canceled the beneficial effects of AhR ligands on experimental AIP. Serum IL-22 concentrations were elevated in patients with type 1 AIP after the induction of remission with prednisolone. These data suggest that AhR activation suppresses chronic fibroinflammatory reactions that characterize AIP via IL-22 produced by pancreatic islet α cells.

Indole-3-pyruvic acid alleviates rheumatoid arthritis via the aryl hydrocarbon receptor pathway.

Background: In previous studies, we found that smoking may participate in the pathogenesis of rheumatoid arthritis (RA) via the aryl hydrocarbon receptor (AhR) pathway. However, when we conducted a subgroup analysis, the expression of AhR and CYP1A1 in healthy people was higher than that in RA patients. We considered that endogenous AhR ligands may exist in vivo that activate AhR to play a protective role. Indole-3-pyruvic acid (IPA) is a tryptophan (Trp) metabolite produced by the indole pathway and serves as a ligand of AhR. This study aimed to reveal the effect and mechanism of IPA in RA. Methods: A total of 14 patients with RA and 14 healthy volunteers were enrolled. The differential metabolites were screened with liquid chromatography-mass spectrometry (LC-MS) metabolomics technology. We also treated peripheral blood mononuclear cells (PBMCs) with IPA to evaluate the effect on the differentiation of T helper 17 (Th17) cells or regulatory T (Treg) cells. To determine whether IPA can be used to alleviate RA, we administered IPA to rats with collagen-induced arthritis (CIA). Methotrexate was used as a standard drug for CIA. Results: When the dose reached 20 mg/kg/d, the severity of CIA was significantly reduced. In vitro experiments verified that IPA inhibited the differentiation of Th17 cells and promoted the differentiation of Treg cells, but this effect was weakened by CH223191. Conclusions: IPA is a protective factor for RA; it can restore the Th17/Treg cell balance through the AhR pathway, which can alleviate RA.

Phytochemical Profile of Trigonella caerulea (Blue Fenugreek) Herb and Quantification of Aroma-Determining Constituents.

The herb of Trigonella caerulea (Fabaceae), commonly known as blue fenugreek, is used for the production of traditional cheese and bread varieties in the Alpine region. Despite its frequent consumption, only one study so far has focused on the constituent pattern of blue fenugreek, revealing qualitative information on some flavor-determining constituents. However, with regard to the volatile constituents present in the herb, the applied methods were insufficient and did not take relevant terpenoids into account. In the present study, we analyzed the phytochemical composition of T. caerulea herb applying a set of analytical methods, such as headspace-GC, GC-MS, LC-MS, and NMR spectroscopy. We thus determined the most dominant primary and specialized metabolites and assessed the fatty acid profile as well as the amounts of taste-relevant α-keto acids. In addition, eleven volatiles were quantified, of which tiglic aldehyde, phenylacetaldehyde, methyl benzoate, n-hexanal, and trans-menthone were identified as most significantly contributing to the aroma of blue fenugreek. Moreover, pinitol was found accumulated in the herb, whereas preparative works led to the isolation of six flavonol glycosides. Hence, our study shows a detailed analysis of the phytochemical profile of blue fenugreek and provides an explanation for its characteristic aroma and its health-beneficial effects.

Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response.

Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1, p ≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (p ≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments.

The Production of Pyruvate in Biological Technology: A Critical Review.

Pyruvic acid has numerous applications in the food, chemical, and pharmaceutical industries. The high costs of chemical synthesis have prevented the extensive use of pyruvate for many applications. Metabolic engineering and traditional strategies for mutation and selection have been applied to microorganisms to enhance their ability to produce pyruvate. In the past decades, different microbial strains were generated to enhance their pyruvate production capability. In addition to the development of genetic engineering and metabolic engineering in recent years, the metabolic transformation of wild-type yeast, E. coli, and so on to produce high-yielding pyruvate strains has become a hot spot. The strategy and the understanding of the central metabolism directly related to pyruvate production could provide valuable information for improvements in fermentation products. One of the goals of this review was to collect information regarding metabolically engineered strains and the microbial fermentation processes used to produce pyruvate in high yield and productivity.

The Effects of Iron on In Silico Simulated Abiotic Reaction Networks.

Iron is one of the most abundant elements in the Universe and Earth's surfaces, and undergoes a redox change of approximately 0.77 mV in changing between its +2 and +3 states. Many contemporary terrestrial organisms are deeply connected to inorganic geochemistry via exploitation of this redox change, and iron redox reactions and catalysis are known to cause significant changes in the course of complex abiotic reactions. These observations point to the question of whether iron may have steered prebiotic chemistry during the emergence of life. Using kinetically naive in silico reaction modeling we explored the potential effects of iron ions on complex reaction networks of prebiotic interest, namely the formose reaction, the complexifying degradation reaction of pyruvic acid in water, glucose degradation, and the Maillard reaction. We find that iron ions produce significant changes in the connectivity of various known diversity-generating reaction networks of proposed prebiotic significance, generally significantly diversifying novel molecular products by ~20%, but also adding the potential for kinetic effects that could allow iron to steer prebiotic chemistry in marked ways.

Urine NMR Metabolomics for Precision Oncology in Colorectal Cancer.

Metabolomics is a fundamental approach to discovering novel biomarkers and their potential use for precision medicine. When applied for population screening, NMR-based metabolomics can become a powerful clinical tool in precision oncology. Urine tests can be more widely accepted due to their intrinsic non-invasiveness. Our review provides the first exhaustive evaluation of NMR metabolomics for the determination of colorectal cancer (CRC) in urine. A specific search in PubMed, Web of Science, and Scopus was performed, and 10 studies met the required criteria. There were no restrictions on the query for study type, leading to not only colorectal cancer samples versus control comparisons, but also prospective studies of surgical effects. With this review, all compounds in the included studies were merged into a database. In doing so, we identified up to 100 compounds in urine samples, and 11 were found in at least three articles. Results were analyzed in three groups: case (CRC and adenomas)/control, pre-/post-surgery, and combining both groups. When combining the case-control and the pre-/post-surgery groups, up to twelve compounds were found to be relevant. Seven down-regulated metabolites in CRC were identified, creatinine, 4-hydroxybenzoic acid, acetone, carnitine, d-glucose, hippuric acid, l-lysine, l-threonine, and pyruvic acid, and three up-regulated compounds in CRC were identified, acetic acid, phenylacetylglutamine, and urea. The pathways and enrichment analysis returned only two pathways significantly expressed: the pyruvate metabolism and the glycolysis/gluconeogenesis pathway. In both cases, only the pyruvic acid (down-regulated in urine of CRC patients, with cancer cell proliferation effect in the tissue) and acetic acid (up-regulated in urine of CRC patients, with chemoprotective effect) were present.

A Split Face Comparative Study to Evaluate the Efficacy of 40% Pyruvic Acid vs. Microdermabrasion with 40% Pyruvic Acid on Biomechanical Skin Parameters in the Treatment of Acne Vulgaris.

The synergy of cosmetic acids, with their keratolytic and antibacterial properties, with the mechanical exfoliation of the epidermis brings faster and better treatment results. The aim of the study was to compare the effects of using only pyruvic acid and the synergy of microdermabrasion and chemical exfoliation. In total, 14 women diagnosed with acne took part in the study. Two areas were marked on the participants' faces: the right side (microdermabrasion treatment and a preparation containing pyruvic acid 40%) and the left side (preparation containing pyruvic acid 40%) without mechanical exfoliation. A series of four treatments was performed at 2-week intervals. Skin parameters such as stratum corneum hydration and sebum secretion were measured. Before the treatments, all patients had moderate acne according to GAGS (Min: 19, Max: 22, Md: 20), and after the treatments, it decreased to mild acne according to GAGS (Min: 13, Max: 17, Md: 140). On the right side of the face, there was a statistically significant reduction in sebum secretion in all the examined areas of the face and increase in the hydration of the stratum corneum. On the left side of the face, the differences were also observed in the decrease of sebum value and increase of hydration level; however, they were smaller than on the right side. The use of microdermabrasion in combination with pyruvic acid led to better results in the case of increased hydration and reduction of sebum secretion than using only pyruvic acid treatment.

Synthesis and Antimycobacterial Activity of Isoniazid Derivatives Tethered with Aliphatic Amines.

BACKGROUND: There is an urgent need for new antitubercular compounds. Modification of antimycobacterial isonicotinohydrazide at hydrazide N2 provided antimycobacterial active compounds. OBJECTIVE: Combining this scaffold with various aliphatic amines that are also frequently present in antitubercular compounds, we have designed, synthesized, and evaluated twenty-three N- (cyclo)alkyl-2-(2-isonicotinoylhydrazineylidene)propanamides and their analogues as potential antimycobacterial compounds. By increasing lipophilicity, we intended to facilitate the penetration of mycobacteria's highly impermeable cell wall. METHODS: The target amides were prepared via condensation of isoniazid and pyruvic acid, followed by carbodiimide-mediated coupling with yields from 35 to 98 %. The compounds were screened against Mycobacterium tuberculosis H37Rv and two nontuberculous mycobacteria (M. avium, M. kansasii). RESULTS: All the derivatives exhibited low minimum inhibitory concentrations (MIC) from ≤0.125 and 2 µM against M. tuberculosis and nontuberculous mycobacteria, respectively. The most active molecules were substituted by a longer n-alkyl from C8 to C14. Importantly, the compounds showed comparable or even several-fold lower MIC than parent isonicotinohydrazide. Based on in silico predictions, a vast majority of the derivatives share suitable physicochemical properties and structural features for drug-likeness. CONCLUSION: Presented amides are promising antimycobacterial agents.

Structure of the K98 capsular polysaccharide from Acinetobacter baumannii REV-1184 containing a cyclic pyruvic acid acetal.

The K98 capsular polysaccharide (CPS) from the Acinetobacter baumannii clinical isolate, REV-1184, was studied by sugar analysis and Smith degradation along with one- and two-dimensional 1H and 13C NMR spectroscopy and high-resolution electrospray ionization mass spectrometry. The CPS was found to consist of linear tetrasaccharide repeats (K-units) that include one residue each of d-GlcpNAc, d-GalpNAc, 2-acetamido-2-deoxy-d-galacturonic acid (d-GalpNAcA), and 2-acetamido-2,6-dideoxy-d-glucose (N-acetylquinovosamine, d-QuipNAc), with the GalpNAc residue decorated with a (R)-configurated 4,6-pyruvic acid acetal group. The CPS has a similar composition to that of A. baumannii K4 but the topology of the tetrasaccharide K-unit is different (linear in K98 versus branched in K4). This was due to a difference in sequence for the Wzy polymerases encoded by the CPS biosynthesis gene clusters KL98 and KL4, with the WzyK98 polymerase forming a ß-d-QuipNAc-(1→3)-d-GalpNAc linkage between the K98 units.

Biochemical and Botanical Aspects of Allium sativum L. Sowing.

The main aim of this study was to evaluate the yield and compliance of selected Iranian garlic (Allium sativum L.) cultivars, including Tuyserkan (TSN), Heydareh (HDH), Mouien (MUN), and Taroom (TRM), during two growing seasons. The TRM cultivar germination rate is higher than the other cultivars studied. The TRM cultivars have quite remarkable values for the dry weight, fresh weight, stem diameter, and the number of leaves present. The fresh weight and dry weight of the TRM cultivar for the second year are 33.8 t/ha and 16.7 t/ha, respectively. However, on average, the HDH cultivar is the tallest plant in the experiments. Average pyruvic acid content in fresh samples of the TRM and HDH cultivars is 78 µm/gfw and 69.3 µm/gfw, respectively. It is observed that there are remarkable differences in the level of pyruvic acid between the different cultivars. The growth, development, and yield of plants are highly dependent on their genetic characteristics; in this experiment, the TRM cultivar shows a good yield (16.7 t/ha), and the evaluated characteristics improve compared to the other cultivars studied, which could be due to the high compatibility of this cultivar to the environmental conditions of the study. The excellent performance on the yield of TRM makes this cultivar more appreciable on a commercial level.

Structural and biochemical basis for the substrate specificity of Pad-1, an indole-3-pyruvic acid aminotransferase in auxin homeostasis.

Phytohormone indole-3-acetic acid (IAA) plays a vital role in regulating plant growth and development. Tryptophan-dependent IAA biosynthesis participates in IAA homeostasis by producing IAA via two sequential reactions, which involve a conversion of tryptophan to indole-3-pyruvic acid (IPyA) by tryptophan aminotransferase (TAA1) followed by the irreversible formation of IAA in the second reaction. Pad-1 from Solanaceae plants regulates IAA levels by catalyzing a reverse reaction of the first step of IAA biosynthesis. Pad-1 is a pyridoxal phosphate (PLP)-dependent aminotransferase, with IPyA as the amino acceptor and l-glutamine as the amino donor. Currently, the structural and functional basis for the substrate specificity of Pad-1 remains poorly understood. In this study, we carried out structural and kinetic analyses of Pad-1 from Solanum melongena. Pad-1 is a homodimeric enzyme, with coenzyme PLP present between a central large α/ß domain and a protruding small domain. The active site of Pad-1 includes a vacancy near the phosphate group (P-side) and the 3'-O (O-side) of PLP. These features are distinct from those of TAA1, which is homologous in an overall structure with Pad-1 but includes only the P-side region in the active site. Kinetic analysis suggests that P-side residues constitute a binding pocket for l-glutamine, and O-side residues of Phe124 and Ile350 are involved in the binding of IPyA. These studies illuminate distinct differences in the active site between Pad-1 and TAA1, and provide structural and functional insights into the substrate specificity of Pad-1.

The efficacy and tolerability of 40% pyruvic acid peel on acne vulgaris, post acne scar and hyperpigmentation in Indians.

INTRODUCTION: Pyruvic acid in concentration between 40% and 70% is currently been used as a superficial to medium peeling agent for various dermatological indications including acne. However, there is a paucity of its efficacy studies on acne in Asians, particularly in Indian skin. AIM: Our study was aimed at determining the efficacy and tolerability of 40% pyruvic acid on acne, post-acne hyperpigmentation, and scarring. MATERIALS AND METHODS: A total of 30 patients with active acne, post-acne scarring, and hyperpigmentation were included. Patients already on oral antibiotic or topical antiacne medication for the last 4 weeks, a history of hypertrophic scarring, keloids, active or recurrent herpes were excluded. Chemical peeling was done at 2 weekly interval from 0 to 12 weeks. An objective assessment of active acne lesions, post-acne scarring, and hyperpigmentation was made at each visit that is at 0, 4,8,12, and 24 weeks. Patients were followed up 2 weeks after the last peel and again at 24 weeks. Permission from the ethical committee was also obtained. RESULTS: There was significant decrease in the number of comedones at 12 weeks compared with 0 week (p = 0.001). Similarly, the number of papules decreased from o weeks to 12 weeks (p value 0.004). Acne score improved from 0 weeks to 12 weeks (p < 0.0001); from 0 weeks to 24 weeks (p = 0.011). and hyperpigmentation improved from 0 weeks to 12 weeks (p = 0.008); from 0 weeks to 24 weeks (p = 0.021). CONCLUSION: Our study showed a significant decrease in comedones, papules, acne score, and hyperpigmentation, though acne scar did not improve significantly. However, a study with larger sample is needed due to the limited number of patient population in our study.