Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

A review of long-term change in surface water natural organic matter concentration in the northern hemisphere and the implications for drinking water treatment.

Reduced atmospheric acid deposition has given rise to recovery from acidification - defined as increasing pH, acid neutralization capacity (ANC), or alkalinity in surface waters. Strong evidence of recovery has been reported across North America and Europe, driving chemical responses. The primary chemical responses identified in this review were increasing concentration and changing character of natural organic matter (NOM) towards predominantly hydrophobic nature. The concentration of NOM also influenced trace metal cycling as many browning surface waters also reported increases in Fe and Al. Further, climate change and other factors (e.g., changing land use) act in concert with reductions in atmospheric deposition to contribute to widespread browning and will have a more pronounced effect as deposition stabilizes. The observed water quality trends have presented challenges for drinking water treatment (e.g., increased chemical dosing, poor filter operations, formation of disinfection by-products) and many facilities may be under designed as a result. This comprehensive review has identified key research areas to be addressed, including 1) a need for comprehensive monitoring programs (e.g., larger timescales; consistency in measurements) to assess climate change impacts on recovery responses and NOM dynamics, and 2) a better understanding of drinking water treatment vulnerabilities and the transition towards robust treatment technologies and solutions that can adapt to climate change and other drivers of changing water quality.

APDM gait and balance measures fail to predict symptom progression rate in Parkinson's disease.

Parkinson's disease (PD) results in progressively worsening gait and balance dysfunction that can be measured using computerized devices. We utilized the longitudinal database of the Parkinson's Disease Biomarker Program to determine if baseline gait and balance measures predict future rates of symptom progression. We included 230, 222, 164, and 177 PD subjects with 6, 12, 18, and 24 months of follow-up, respectively, and we defined progression as worsening of the following clinical parameters: MDS-UPDRS total score, Montreal Cognitive Assessment, PDQ-39 mobility subscale, levodopa equivalent daily dose, Schwab and England score, and global composite outcome. We developed ridge regression models to independently estimate how each gait or balance measure, or combination of measures, predicted progression. The accuracy of each ridge regression model was calculated by cross-validation in which 90% of the data were used to estimate the ridge regression model which was then tested on the 10% of data left out. While the models modestly predicted change in outcomes at the 6-month follow-up visit (accuracy in the range of 66-71%) there was no change in the outcome variables during this short follow-up (median change in MDS-UPDRS total score = 0 and change in LEDD = 0). At follow-up periods of 12, 18, and 24 months, the models failed to predict change (accuracy in the held-out sets ranged from 42 to 60%). We conclude that this set of computerized gait and balance measures performed at baseline is unlikely to help predict future disease progression in PD. Research scientists must continue to search for progression predictors to enhance the performance of disease modifying clinical trials.

Tick paralysis in a free-ranging bobcat (Lynx rufus).

CASE DESCRIPTION: A free-ranging male bobcat (Lynx rufus) was evaluated because of signs of pelvic limb paralysis. CLINICAL FINDINGS: Physical examination of the anesthetized animal revealed tick infestation, normal mentation, and a lack of evidence of traumatic injuries. Radiography revealed no clinically relevant abnormalities. Hematologic analysis results were generally unremarkable, and serologic tests for exposure to feline coronavirus, FeLV, FIV, and Toxoplasma gondii were negative. Results of PCR assays for flea- and common tick-borne organisms other than Bartonella clarridgeiae were negative. TREATMENT AND OUTCOME: Ticks were manually removed, and the patient received supportive care and fipronil treatment. The bobcat made a full recovery within 72 hours after treatment for ticks, and a presumptive diagnosis of tick paralysis was made. Identified tick species included Dermacenter variabilis, Amblyomma americanum, and Ixodes scapularis. CLINICAL RELEVANCE: To the authors' knowledge, tick paralysis has not previously been reported in felids outside Australia. This disease should be considered a differential diagnosis in felids, including exotic cats, with signs of neuromuscular disease of unknown etiopathogenesis.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation.

Adverse reactions (ARs) during the infusion of cellular therapy products (CTPs) are common in patients undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively studied pediatric patients undergoing autologous and allogeneic HSCT to determine the incidence and grade of ARs during stem cell infusion and their predictors. We analyzed data from 213 patients (120 allogeneic and 93 autologous) who received at least 1 CTP, totaling 361 infusion episodes. Serious ARs, defined as grade 2 and 3, occurred in 25 and 11% of infusions, respectively. No grade 4 or 5 ARs were noted. Independent risk factors for developing a serious AR included stem cell source (PBSC vs marrow (odds ratio (OR) 1.8, 95% confidence interval (CI): 0.4-9); cord vs marrow (OR 7.3, 95% CI: 1.3-40), overall P=0.0001) but manipulated CTPs were protective (OR 0.4, 95% CI: 0.2-0.7, P=0.004). Unlike previous adult studies, WBC and granulocyte content were not found to be risk factors in this pediatric population. These data suggest that children tolerate higher WBC content during infusion of CTPs and support the use of manipulated CTP, as indicated, to reduce the risk of adverse infusion reactions.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

OBJECTIVE: To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. METHODS: Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. RESULTS: 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. INTERPRETATION: Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program.

Improvement of ethanol productivity and energy efficiency by degradation of inhibitors using recombinant Zymomonas mobilis (pHW20a-fdh).

Toxic compounds, such as formic acid, furfural, and hydroxymethylfurfural (HMF) generated during pretreatment of corn stover (CS) at high temperature and low pH, inhibit growth of Zymomonas mobilis and lower the conversion efficiency of CS to biofuel and other products. The inhibition of toxic compounds is considered as one of the major technical barriers in the lignocellulose bioconversion. In order to detoxify and/or degrade these toxic compounds by the model ethanologenic strain Z. mobilis itself in situ the fermentation medium, we constructed a recombinant Z. mobilis ZM4 (pHW20a-fdh) strain that is capable of degrading toxic inhibitor, formate. This is accomplished by cloning heterologous formate dehydrogenase gene (fdh) from Saccharomyces cerevisiae and by coupling this reaction of NADH regeneration reaction system with furfural and HMF degradation in the recombinant Z. mobilis strain. The NADH regeneration reaction also improved both the energy efficiency and cell physiological activity of the recombinant organism, which were definitely confirmed by the improved cell growth, ethanol yield, and ethanol productivity during fermentation with CS hydrolysate.

Correlates of age at diagnosis of autism spectrum disorders in six Canadian regions.

INTRODUCTION: Early identification of autism spectrum disorders (ASD) is important, since earlier exposure to behavioural intervention programs may result in better outcomes for the child. Moreover, it allows families timely access to other treatments and supports. METHODS: Using generalized linear modeling, we examined the association between child and family characteristics and the age at which 2180 children were diagnosed with ASD between 1997 and 2005 in six Canadian regions. RESULTS: A diagnosis of pervasive developmental disorder-not otherwise specified (PDD-NOS) or Asperger syndrome, rural residence, diagnosis in more recent years, and foreign birthplace were associated with a later age at diagnosis. Children who are visible minorities or who have siblings with ASD were more likely to be diagnosed earlier. Collectively, these factors explained little of the variation in age at diagnosis, however. CONCLUSION: While it is encouraging that ethnocultural identity, neighbourhood income, urban or rural residence, and sex of the child were not major contributors to disparities in the age when children were identified with ASD, more work is needed to determine what does account for the differences observed. Regional variations in the impact of several factors suggest that aggregating data may not be an optimal strategy if the findings are meant to inform policy and clinical practice at the local level.

Design and construction of improved new vectors for Zymomonas mobilis recombinants.

Zymomonas mobilis is a very important gram-negative bacterium having a potential application to simultaneous co-production of biofuel and other high value-added products through biorefinery process technology development. Up to now, pLOI193 has been used as the plasmid of choice for Z. mobilis strains. However, its application has been limited due to its relatively low transformation efficiency, a large plasmid size (13.4 kb), and limited choice of cloning sites for gene manipulations. Some of these limitations can be overcome by the newly designed and constructed plasmid pHW20a, which provides significantly higher transformation efficiency (about two orders of magnitude greater), better stability (for at least 120 generation times), and an ease of gene manipulations. The pHW20a contains three complete cis-acting genes (repA, repB, and repC) encoding the Rep proteins for primosome formation. It has the origin of replication (oriV) to ensure replication in gram-negative bacteria, two mob genes that enhances transformation efficiency, a screening marker (lacZα), expanded multiple cloning sites (MCS) that enables easy gene manipulation, and the tetracycline resistance gene (tc(r) ). The utility of screening marker, lacZα with MCS, was confirmed by the blue-white screening test. Several examples of applications of gene expression in Z. mobilis ZM4 have been demonstrated in this article by using several new pHW20a-derived plasmids and expressing the homologous genes (gfo and ppc) and the heterologous genes (bglA, mdh, and fdh1). The results show that pHW20a is a very useful new vector for construction of new Z. mobilis recombinant strains that will enable simultaneous co-production of biofuel and high value added products.

Sorbitol production using recombinant Zymomonas mobilis strain.

A recombinant Zymomonas mobilis strain harboring the plasmid pHW20a-gfo for over-expression of glucose-fructose oxidoreductase (GFOR) was constructed. The specific activity of GFOR enzyme in the new recombinant strain was at least two folds greater than that in the wild strain. The maximum GFOR activity achieved in terms of the volumetric, and the cellular were 2.59 U ml(-1), and 0.70 U mg(-1), respectively, in the batch cultures. A significant improvement of the bioconversion process for the production of sorbitol and gluconic acid from glucose and fructose was made using divalent metal ions which drastically reduced the ethanol yield and significantly increased the yield of target product. Among several divalent metal ions evaluated, Zn(2+) was found to be most effective by inhibiting the Entner-Doudoroff pathway enzymes. The yield of the byproduct ethanol was reduced from 16.7 to 1.8 gl(-1) and the sorbitol yield was increased to almost 100% from 89%. The Ca(2+) enhanced the sorbitol yield and the formation of calcium gluconate salt made the separation of gluconate from the reaction system easier.

Screening of oleaginous yeast strains tolerant to lignocellulose degradation compounds.

High cost of triacylglycerol lipid feedstock is the major barrier for commercial production of biodiesel. The fermentation of oleaginous yeasts for lipid production using lignocellulose biomass provides a practical option with high economic competitiveness. In this paper, the typical oleaginous yeast strains were screened under the pressure of lignocellulose degradation compounds for selection of the optimal strains tolerant to lignocellulose. The inhibitory effect of lignocellulose degradation products on the oleaginous yeast fermentation was carefully investigated. Preliminary screening was carried out in the minimum nutritious medium without adding any expensive complex ingredients then was carried out in the lignocellulosic hydrolysate pretreated by dilute sulfuric acid. Seven typical lignocellulose degradation products formed in various pretreatment and hydrolysis processing were selected as the model inhibitors, including three organic acids, two furan compounds, and two phenol derivatives. The inhibition of the degradation compounds on the cell growth and lipid productivity of the selected oleaginous yeasts were examined. Acetic acid, formic acid, furfural, and vanillin were found to be the strong inhibitors for the fermentation of oleaginous yeasts, while levulinic acid, 5-hydroxymethylfurfural, and hydroxybenzaldehyde were relatively weak inhibitors. Trichosporon cutaneum 2.1374 was found to be the most adopted strain to the lignocellulose degradation compounds.

Carbon and energy balances of glucose fermentation with hydrogenproducing bacterium Citrobacter amalonaticus Y19.

For the newly isolated H2-producing chemoheterotrophic bacterium Citrobacter amalonaticus Y19, anaerobic glucose metabolism was studied in batch cultivation at varying initial glucose concentrations (3.5- 9.5 g/l). The carbon-mass and energy balances were determined and utilized to analyze the carbon metabolic-pathways network. The analyses revealed (a) variable production of major metabolites (H2, ethanol, acetate, lactate, CO2, and cell mass) depending on initial glucose levels; (b) influence of NADH regeneration on the production of acetate, lactate, and ethanol; and (c) influence of the molar production of ATP on the production of biomass. The results reported in this paper suggest how the carbon metabolic pathway(s) should be designed for optimal H2 production, especially at high glucose concentrations, such as by blocking the carbon flux via lactate dehydrogenase from the pyruvate node.

Co-occurring disorders: a possible key to visual perceptual deficits in children with developmental coordination disorder?

A study was conducted to examine how visual perceptual functioning in children with DCD may be influenced by co-occurring learning problems such as reading disabilities (RD) and/or attention deficit hyperactivity disorder (ADHD). Participants included seven groups of children: 27 children with DCD only, 11 with ADHD only, 14 with RD only, 63 with DCD and at least one other disorder (i.e., DCD + ADHD, DCD + RD, DCD + ADHD + RD), and 73 typically developing controls. Visual perceptual skills were assessed using the Test of Visual Perceptual Skills (TVPS) and the Rey Osterreith Complex Figure (ROCF; copy and delayed recall). Children with DCD and at least one other disorder were found to have impairments on the TVPS compared to children with DCD only, ADHD only, and typically developing controls, particularly on subtests assessing visual memory. On the ROCF, children with DCD and at least one other disorder scored significantly lower than children with ADHD only or RD only. Children with DCD plus one other disorder were then subdivided into three groups: DCD + ADHD, DCD + RD, and DCD + ADHD + RD and compared to children with DCD only, ADHD only, and RD only. Results indicated that children with DCD + ADHD + RD had significant impairments on the TVPS compared to children with DCD only and children with ADHD only. On the ROCF, children with DCD + ADHD + RD scored significantly lower than all of the groups, except the DCD+RD group. These findings suggest that DCD on its own is not associated with visual perceptual problems; rather, it is the presence of co-occurring disorders that is a possible key to visual perceptual deficits in children with DCD. The number of co-occurring disorders present with DCD is associated with the severity of the visual perceptual dysfunction. Deficits in visual memory skills appear to be a specific area of difficulty for children with DCD and co-occurring RD and/or ADHD.

Total biosynthesis of deoxynucleoside triphosphates using deoxynucleoside monophosphate kinases for PCR application.

Polymerase chain reaction (PCR) and other PCR applications for DNA synthesis require deoxynucleoside triphosphates (dNTP) as the essential precursors and substrates. Currently, the dNTP is commercially produced by a chemical method which is environmentally hazardous and costly due to its low yields in both the synthetic reaction and purification processes. In this study, a enzyme technology for the total integrated biosynthesis of all dNTP components is presented. The bioprocess technology developed and reported here involves two sequential enzymatic phosphorylation reactions coupled with the cofactor regeneration starting from deoxynucleoside monophosphates (dNMP) to deoxynucleoside diphosphates (dNDP) in the first reaction step and to dNTP in the second reaction step in the same bioreactor. The four genes encoding these deoxynucleoside monophosphate kinases were cloned into the recombinant E. coli and expressed using the recombinant E. coli strains. The reaction mechanisms and kinetics of the four kinase enzymes are studied and reported. The total enzymatic syntheses of the four dNTP products were carried out in four separate operations under the high substrate concentrations which emulate the practical application. The optimal process conditions were carefully investigated and complete conversion of dNMP to dNTP at high substrate concentration have been achieved. The purity and quality of dNTP products obtained from this work were analyzed and found to be at least equivalent or better than the commercially available dNTP products. The PCR application of dNTP products obtained from this work were also evaluated for isolating and amplifying genes of different sizes from different organisms. The PCR performance test also showed an equivalent quality as compared to the commercially available dNTP. The bioprocess technology developed and reported here for production of dNTP will provide economically competitive and environmentally friendly viable technology for the industry and research community as compared to the chemical technology currently in use.

Comorbidity, co-occurrence, continuum: What's in a name?

BACKGROUND: Comorbidity, co-occurrence and continuum are three terms used when referring to developmental problems such as Developmental Coordination Disorder (DCD), but they can be confusing and misleading. Further, the terms can be upsetting to parents, and are not always helpful in guiding the selection of clinical interventions. GOALS: The main purpose of this paper is to question some of the terminology we employ when referring to DCD and other developmental problems. A secondary purpose is to discuss some of the conceptual frameworks that have been proposed that attempt to address the issue of the interrelationships among developmental problems. APPROACH: The terminology is examined by first referring to the basic dictionary definitions. Second, data we have published that relate to the issues of co-occurrence and continuum are reviewed in light of the terminology questions. Finally, we review some alternative conceptual frameworks which more accurately describe the relationships among developmental problems. CONCLUSION: The term 'comorbidity' has limited relevance to developmental problems, and its use is questionable. In contrast, co-occurrence and continuum are more useful terms to use in regard to developmental problems. Concepts such as atypical brain development and minor neurological dysfunction provide some possible explanations for the increased levels of co-occurrence of developmental disorders in children who are more severely affected.

Substrate specificity of nonribosomal peptide synthetase modules responsible for the biosynthesis of the oligopeptide moiety of cephabacin in Lysobacter lactamgenus.

Lysobacter lactamgenus produces cephabacins, a class of beta-lactam antibiotics which have an oligopeptide moiety attached to the cephem ring at the C-3 position. The nonribosomal peptide synthetase (NRPS) system, which comprises four distinct modules, is required for the biosynthesis of this short oligopeptide, when one takes the chemical structure of these antibiotics into consideration. The cpbI gene, which has been identified in a region upstream of the pcbAB gene, encodes the NRPS - polyketide synthase hybrid complex, where NRPS is composed of three modules, while the cpbK gene -- which has been reported as being upstream of cpbI-- comprises a single NRPS module. An in silico protein analysis was able to partially reveal the specificity of each module. The four recombinant adenylation (A) domains from each NRPS module were heterologously expressed in Escherichia coli and purified. Biochemical data from ATP-PPi exchange assays indicated that L-arginine was an effective substrate for the A1 domain, while the A2, A3 and A4 domains activated L-alanine. These findings are in an agreement with the known chemical structure of cephabacins, as well as with the anticipated substrate specificity of the NRPS modules in CpbI and CpbK, which are involved in the assembly of the tetrapeptide at the C-3 position.

Cloning of deoxynucleoside monophosphate kinase genes and biosynthesis of deoxynucleoside diphosphates.

The genes encoding four deoxynucleoside monophosphate kinase (dNMP kinase) enzymes, including ADK1 for deoxyadenylate monophosphate kinase (AK), GUK1 for deoxyguanylate monophosphate kinase (GK), URA6 for deoxycytidylate monophosphate kinase (CK), and CDC8 for deoxythymidylate monophosphate kinase (TK), were isolated from the genome of Saccharomyces cerevisiae ATCC 2610 strain and cloned into E. coli strain BL21(DE3). Four recombinant plasmids, pET17b-JB1 containing ADK1, pET17b-JB2 containing GUK1, pET17b-JB3 containing URA6, and pET17b-JB4 containing CDC8, were constructed and transformed into E. coli strain for over-expression of AK, GK, CK, and TK. The amino acid sequences of these enzymes were analyzed and a putative conserved peptide sequence for the ATP active site was proposed. The four deoxynucleoside diphosphates (dNDP) including deoxyadenosine diphosphate (dADP), deoxyguanosine diphosphate (dGDP), deoxycytidine diphosphate (dCDP), and deoxythymidine diphosphate (dTDP), were synthesized from the corresponding deoxynucleoside monophosphates (dNMP) using the purified AK, GK, CK, and TK, respectively. The effects of pH and magnesium ion concentration on the dNDP biosynthesis were found to be important. A kinetic model for the synthetic reactions of dNDP was developed based on the Bi-Bi random rapid equilibrium mechanism. The kinetic parameters including the maximum reaction velocity and Michaelis-Menten constants were experimentally determined. The study on dNDP biosynthesis reported in this article are important to the proposed bioprocess for production of deoxynucleoside triphosphates (dNTP) that are used as precursors for in vitro DNA synthesis. There is a significant advantage of using enzymatic biosyntheses of dNDP as compared to the chemical method that has been in commercial use.

Biosynthesis reaction mechanism and kinetics of deoxynucleoside triphosphates, dATP and dGTP.

The enzyme reaction mechanism and kinetics for biosyntheses of deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP) from the corresponding deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) catalyzed by pyruvate kinase were studied. A kinetic model for this synthetic reaction was developed based on a Bi-Bi random rapid equilibrium mechanism. Kinetic constants involved in this pyruvate kinase catalyzed phosphorylation reactions of deoxynucleoside diphosphates including the maximum reaction velocity, Michaelis-Menten constants, and inhibition constants for dATP and dGTP biosyntheses were experimentally determined. These kinetic constants for dATP and dGTP biosyntheses are of the same order of magnitude but significantly different between the two reactions. Kinetic constants involved in ATP and GTP biosyntheses as reported in literature are about one order of magnitude different from those involved in dATP and dGTP biosyntheses. This enzyme reaction requires Mg2+ ion and the optimal Mg2+ concentration was also determined. The experimental results showed a very good agreement with the simulation results obtained from the kinetic model developed. This kinetic model can be applied to the practical application of a pyruvate kinase reaction system for production of dATP and dGTP. There is a significant advantage of using enzymatic biosyntheses of dATP and dGTP as compared to the chemical method that has been in commercial use.