An examination of the carbon metabolic pathways in Acinetobacter sp. TAC-1 in the context of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) utilization / 生物工程学报

The present study aimed to unravel the carbon metabolism pathway of Acinetobacter sp. TAC-1, a heterotrophic nitrification-aerobic denitrification (HN-AD) strain that utilizes poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as a carbon source. Sodium acetate was employed as a control to assess the gene expression of carbon metabolic pathways in the TAC-1 strain. The results of genome sequencing demonstrated that the TAC-1 strain possessed various genes encoding carbon metabolic enzymes, such as gltA, icd, sucAB, acs, and pckA. KEGG pathway database analysis further verified the presence of carbon metabolism pathways, including the glycolytic pathway (EMP), pentose phosphate pathway (PPP), glyoxylate cycle (GAC), and tricarboxylic acid (TCA) cycle in the TAC-1 strain. The differential expression of metabolites derived from distinct carbon sources provided further evidence that the carbon metabolism pathway of TAC-1 utilizing PHBV follows the sequential process of PHBV (via the PPP pathway)→gluconate (via the EMP pathway)→acetyl-CoA (entering the TCA cycle)→CO2+H2O (generating electron donors and releasing energy). This study is expected to furnish a theoretical foundation for the advancement and implementation of novel denitrification processes based on HN-AD and solid carbon sources.

Progress in One-carbon Metabolism and Tumor Therapy / 肿瘤防治研究

In recent years, it has already run into a common view that "tumor is a metabolic disease", and the reprogramming of tumor metabolism has become the focus of current research. One-carbon metabolism involves folate cycle, methionine cycle and trans-sulfuration pathway. By utilizing these three ways, one carbon unit can regulate tumor growth and proliferation with the production of pyrimidine, thymidine, s-adenosine, glutathione, etc. This paper mainly describes the production and utilization of one carbon unit in tumor, as well as the interaction between one carbon metabolism and tumor development, providing new ideas for studying the mechanism of one-carbon metabolism in tumorigenesis and the treatment of nutrients in tumor.

Mitochondrial dysfunction in neural tube defects / 国际儿科学杂志

Neural tube defects are a group of severe congenital malformations, including anencephaly, spina bifida, and encephalocele, which happen when neural tube fails to achieve proper closure during early embryogenesis.Mitochondria are an important site for biological oxidation and substance metabolism, as well as an important component in maintaining homeostasis of the intracellular environment.Mitochondria are also involved in the process of oocyte maturation, fertilization and embryonic development.Normal function of mitochondria is the key to the normal development of embryos.Therefore, mitochondrial dysfunction may be one of the mechanisms of neural tube closure failure.Slc25a32, SHMT2, MTHFD2/MTHFD2L, MTHFD1L and glycine cleavage system(GCS)are a series of key molecules of the mitochondrial one-carbon metabolic pathway.This paper reviews the research progress of mitochondrial dysfunction in the pathogenesis of neural tube malformation by starting from several key molecules and combining with the two main metabolic pathways of one-carbon metabolic chain and oxidative respiratory chain.

Effect of Nitrogen Fertilizer on Carbon Metabolism and Growth and Development of Acanthopanax senticosus Seedlings / 中国实验方剂学杂志

Objective::To study the effect of different nitrogen application rates on the growth and carbon metabolism of Acanthopanax senticosus seedlings, and screen out the rational fertilization conditions, in order to provide basis and guidance for scientific fertilization of artificially cultivated A. senticosus. Method::A single-point, single-factor field experiment was conducted to study the seedlings of growing evenly A. senticosus.Five different nitrogen application treatment groups were set up to treat the seedlings, namely N1 group (30 g·m-2), N2 group (60 g·m-2), N3 group (90 g·m-2), N4 group (120 g·m-2), N5 group (150 g·m-2) and CK group (0 g·m-2), respectively.Three months later, plant height, root circumference, stem circumference, root-shoot ratio and SPAD were measured at harvest time.The contents of protein, sucrose, starch, soluble sugar and reducing sugar in fresh leaves were measured. Result::N3 treatment was the best treatment method for the growth and development of A. senticosus seedlings, and the growth of A. senticosus seedlings was the best under this treatment.The protein content of A. senticosus seedlings in N3 treatment was the highest.Starch and sucrose were best accumulated in N5 treatment group and CK treatment group.N5 treatment had the highest soluble sugar content and reducing sugar content. Conclusion::There is a dose-effect relationship between the growth and development of A. senticosus seedlings; that is to say, low and high nitrogen application treatments will cause stress on A. senticosus seedlings.In conclusion, the suitable nitrogen application rate for A. senticosus growth is 90-120 g·m-2.

Optimizing carbon/energy metabolism to enhance monellin production by Pichia pastoris / 生物工程学报

In heterologous protein productions by Pichia pastoris, methanol induction is generally initiated when cell density reaches very high level. However, this traditional strategy suffers with the problems of difficulty in DO control, toxic by-metabolites accumulation and low targeted protein titer. Therefore, initiating methanol induction at lower cell concentration is considered as an alternative strategy to overcome those problems. However, the methanol/energy regulation mechanisms of initiating induction at lower concentration are not clear and seldom reported. In this article, with monellin production as a prototype, we analyzed the methanol/energy metabolism in protein expression process using the strategies of initiating induction at both higher/lower cells concentrations. We attempted to interpret the advantages of the "alternative" strategy, via online measurements of methanol consumption, CO₂ production and O₂ uptake rates. When adopting this "alternative" strategy and maintaining temperature at 30 °C, carbon flux ratio directing into monellin precursors synthesis reached the highest level of 65%. In addition, monellin synthesis was completely associated with cell growth.

Implicancias clínicas de metiltransferasas de moléculas pequeñas / Clinical implications of small molecule-methyltransferases / Implicações clínicas de metiltransferases de pequenas moléculas

Se encaran las metilaciones naturales y aquellas patológicas relacionadas con disfunciones en el metabolismo de un carbono (C1) correspondiente a los ciclos de folato y de metionina. Dado que las enzimas que intervienen en este tipo de reacciones son las metiltransferasas, se analizan las correspondientes a humanos, y mamíferos en general, dependientes de S-adenosil-L-metionina (SAMe). Un papel importante corresponde a las llamadas metiltransferasas de moléculas pequeñas, las cuales fueron dejadas de lado durante años, pero han resurgido pues algunas intervienen en procesos de alteración de la percepción en humanos. En este trabajo se pone énfasis en la importancia clínica de la activación y/o inhibición de algunas metiltransferasas de moléculas pequeñas, con ejemplos referidos a: feniletanolamina-N-metiltransferasa, catecol-O-metiltransferasa (COMT), histamina-N-metiltransferasa, 5-hidroxiindol-O-metiltransferasa (HOMT) e indoletilamina-N-metiltransferasa (INMT). Se hace un análisis histórico de las metiltransferasas que actúan sobre sustratos indólicos, con énfasis en indol-N-metiltransferasas, en particular indoletilamina-N-metiltransferasa, con sus características y localización, así como su importancia en esquizofrenia. A continuación se analiza la posible etiología de la esquizofrenia, destacando las disfunciones y deterioros generados en los ciclos de folato y de metionina. En este aspecto se analizan las implicancias clínicas de la metilación, con énfasis en la disfunción serotoninérgica en esquizofrenia, ejemplificando con investigaciones de este laboratorio en pacientes y en conejos.

Natural methylations, and those pathological related with dysfunctions in one-carbon metabolism involving the folate and methionine cycles are addressed herein. Since the enzymes that catalyze these reactions are methyltransferases, we analyze those S-adenosyl-L-methionine (SAMe)-dependent enzymes occurring in humans, and mammals in general. An important role is played by the so-called small-molecule methyltransferases, which were neglected for years, but have reappeared as some of them are involved in altering perception in humans. In this work the clinical importance of the activation and/or inhibition of some small-molecule methyltransferases is emphasized, illustrated by reference to phenylethanolamine N-methyltransferase, catechol O-methyltransferase (COMT), histamine N-methyltransferase, 5-hydroxyindole O-methyltransferase (HOMT), and indoleethylamine N-methyltransferase (INMT). A historical analysis of methyltransferases acting on indole substrates is carried out, with emphasis on indole N-methyltransferases, particularly characteristics and location as well as importance in schizophrenia of indoleethylamine N-methyltransferase. Then, the possible etiopathology of schizophrenia is discussed, highlighting malfunctions and damages arising from folate and methionine cycles. In this regard clinical implications of methylation are discussed, with emphasis on serotonergic dysfunction in psychiatric disorders and schizophrenia, exemplifying with research of this laboratory in patients and rabbits.

Metilação naturais, e aqueles patológicas relacionadas com disfunções no metabolismo de um carbono que envolvem os ciclos de folato e metionina são aqui abordados. Como as enzimas envolvidas nestas reacções são metiltransferases, analisamos as enzimas dependentes de S-adenosil-L-metionina (SAMe) que ocorren nos humanos e mamíferos em geral. Um papel importante é desempenhado pelos chamadas metiltransferases de pequenas moléculas, as quais foram negligenciadas por anos, mas ressurgiram como alguns deles estão envolvidos em processos de alterações de percepção em seres humanos. Neste trabalho, a importância clínica da activação e/ou inibição de algumas metiltransferases de pequenas moléculas são enfatizados, ilustrado por referência aos phenylethanolamine N-metiltransferase, catecol O-metiltransferase (COMT), histamina N-metiltransferase, 5-hidroxi-indole O-metiltransferase (HOMT) e indoletilamina N-metiltransferase (INMT). A análise histórica do methyltransferases que actuam em substratos de indole é realizada, com ênfase em indole N-metiltransferases, principalmente indoletilamina N-metiltransferase, com suas características e localização, bem como a sua importância na esquizofrenia. Em seguida, a possível etiologia da esquizofrenia é discutido, destacando as avarias e danos gerados nos ciclos de folato e metionina. Neste aspecto são discutidas as implicações clínicas de metilação, com ênfase na disfunção serotonérgica em esquizofrenia, exemplificando com a investigação deste laboratório em pacientes e coelhos.

Role of CYP1A1 haplotypes in modulating susceptibility to coronary artery disease.

To investigate the role of cytochrome P450 1A1 (CYP1A1) haplotypes in modulating susceptibility to coronary artery disease (CAD), a case-control study was conducted by enrolling 352 CAD cases and 282 healthy controls. PCR-RFLP, multiplex PCR, competitive ELISA techniques were employed for the analysis of CYP1A1 [m1 (T→C), m2 (A→G) and m4 (C→A)] haplotypes, glutathione-S-transferase (GST)T1/GSTM1 null variants and plasma 8-oxo-2’deoxyguanosine (8-oxodG) respectively. Two CYP1A1 haplotypes, i.e. CAC and TGC showed independent association with CAD risk, while all-wild CYP1A1 haplotype i.e. TAC showed reduced risk for CAD. All the three variants showed mild linkage disequilibrium (D’: 0.05 to 0.17). GSTT1 null variant also exerted independent association with CAD risk (OR: 2.53, 95% CI 1.55–4.12). Among the conventional risk factors, smoking showed synergetic interaction with CAC haplotype of CYP1A1 and GSTT1 null genotype in inflating CAD risk. High risk alleles of this pathway showed dose-dependent association with percentage of stenosis and number of vessels affected. Elevated 8-oxodG levels were observed in subjects with CYP1A1 CAC haplotype and GSTT1 null variant. Multiple linear regression model of these xenobiotic variants explained 36% variability in 8-oxodG levels. This study demonstrated the association of CYP1A1 haplotypes and GSTT1 null variant with CAD risk and this association was attributed to increased oxidative DNA damage.

Redução dos níveis séricos de ácido fólico em pacientes com a doença de Alzheimer / Serum folic acid is reduced in patients with Alzheimer's disease

CONTEXTO: Deficiência de vitaminas do complexo B tem sido associada a deterioração cognitiva e quadros demenciais em idosos. OBJETIVO: Neste trabalho, foi avaliado se pacientes com doença de Alzheimer (DA) e com comprometimento cognitivo leve (CCL) apresentam níveis séricos de ácido fólico e cobalamina (vitamina B12) menores que idosos controles. MÉTODOS: Foram recrutados 146 idosos (40 com DA, 56 com CCL e 49 idosos controles) para este estudo. Os níveis séricos de ácido fólico e vitamina B12 foram avaliados pelo método de eletroquimioluminescência. RESULTADOS: Os pacientes com DA apresentaram redução estatisticamente significativa nos níveis de ácido fólico em relação aos idosos com CCL e controles (p = 0,02). Esses resultados mantiveram-se estatisticamente significativos após controlar por variáveis sociodemográficas e desempenho cognitivo. Não se observaram diferenças estatisticamente significativas nos níveis de vitamina B12 nem em variáveis hematológicas entre os grupos. CONCLUSÃO: Esses resultados reforçam a importância de anormalidades em aspectos nutricionais, em particular do metabolismo de um-carbono, na fisiopatologia da DA.

BACKGROUND: Complex B vitamin deficiency has been associated to cognitive impairment and dementing disorders in the elderly. OBJECTIVE: This work aims to assess whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) have lower levels of folic acid and cobalamin (vitamin B12) compared to age and gender-matched controls. METHODS: One hundred and forty six elderly subjects (40 AD, 56 MCI and 49 healthy older adults) were recruited for this study. Serum folic acid and vitamin B12 levels were measured by electrochemoluminescence. RESULTS: Compared to MCI and healthy controls a statistically significant reduction in serum concentrations of folic acid in AD patients was found (p = 0.02). This result remained statistically significant after controlling for socio-demographic and cognitive performance variables (p = 0.01). No significant differences were found in serum concentrations of vitamin B12 in patients with AD, MCI and healthy controls. No significant changes in hematologic parameters were observed across these diagnostic groups. DISCUSSION: The present study provides additional evidence that folic acid is reduced in patients with AD and reinforces the importance of nutritional changes, in particular the one-carbon metabolism, in the physiopathology of AD.

Modulatory effect of plasma folate and polymorphisms in one-carbon metabolism on catecholamine methyltransferase (COMT) H108L associated oxidative DNA damage and breast cancer risk.

The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2’-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5’-UTR 3R2R, TYMS 3’-UTR ins6/del6. Increased plasma 8-oxodG were observed in cases compared to controls (mean ± SE: 5.59 ± 0.60 vs. 3.50 ± 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk.

Advances in Methylotrophy / 微生物学通报

Methylotrophy is a kind of widespread microbe which can use carbon compound as their only carbon and energy sources.It has been reported that methylotrophy can directly use one carbon com-pound to transform into their own metabolic one carbon unit,then these one metabolic one carbon units can be used as energy and carbon skeleton by organisms,which is a main part in one carbon metabolism.Because this is a novel metabolic system,it can be used in the study of biological metabolism and evo-lution.Based on the previous study about Methylobacterium sp.MB200 in our lab,here we summarized the research improvements about methylotrophy from their taxonomy,metabolism,genomics and ap-plications.

Effects of zinc on carbon and nitrogen metabolism in leaves of Pinellia ternata and their yield / 中草药

Objective To find out the proper concentration of ZnSO4?7H2O as foliar fertilizer used for Pinellia ternata, and to provide reference for high yield of P.ternate,effects of zinc on the carbon and nitrogen metabolism in leaves of P.ternata and the yield were studied.Methods Seedlings of P.ternata were employed as the experiment material.At the stage of full seedling,ZnSO4?7H2O of different concentration was sprayed on the leaves,the indexes of carbon and nitrogen metabolism were determined on the day 10,the weight of tubers and bulbils were measured at the sprout tumble stage.Results The yield of P.ternata has an exceedingly significant positive correlation with the contents of soluble sucrose and starch in the leaves,a significant positive correlation with the content of photosynthetic pigment and the aldolase activity,and a negative correlation with the amylase activity.In addition,the yield shows both an exceedingly significant positive correlation whith the nitrate reductase activity and a significant positive correlation with the content of protein.At the stage of full seedling,zinc sprayed on leaves can increase the content of photosynthetic pigment and improve the capability of photosynthesis.Meanwhile,spraying zinc can also promote the accumulation of soluble sucrose and starch in the leaves because of its stimulation on aldolase and inhibition on amylase.Besides,spraying zinc on leaves could improve the activity of nitrate reductase and the content of protein,and finally increase the yield of P.ternata.Conclusion The concentration of 600 mg/L is the best for ZnSO4?7H2O used as foliar fertilizer for P.ternate at the stage of full seedling.