An organic O donor for biological hydroxylation reactions.

All biological hydroxylation reactions are thought to derive the oxygen atom from one of three inorganic oxygen donors, O2, H2O2, or H2O. Here, we have identified the organic compound prephenate as the oxygen donor for the three hydroxylation steps of the O2-independent biosynthetic pathway of ubiquinone, a widely distributed lipid coenzyme. Prephenate is an intermediate in the aromatic amino acid pathway and genetic experiments showed that it is essential for ubiquinone biosynthesis in Escherichia coli under anaerobic conditions. Metabolic labeling experiments with 18O-shikimate, a precursor of prephenate, demonstrated the incorporation of 18O atoms into ubiquinone. The role of specific iron-sulfur enzymes belonging to the widespread U32 protein family is discussed. Prephenate-dependent hydroxylation reactions represent a unique biochemical strategy for adaptation to anaerobic environments.

Activation of Coq6p, a FAD Monooxygenase Involved in Coenzyme Q Biosynthesis, by Adrenodoxin Reductase/Ferredoxin.

Adrenodoxin reductase (AdxR) plays a pivotal role in electron transfer, shuttling electrons between NADPH and iron/sulfur adrenodoxin proteins in mitochondria. This electron transport system is essential for P450 enzymes involved in various endogenous biomolecules biosynthesis. Here, we present an in-depth examination of the kinetics governing the reduction of human AdxR by NADH or NADPH. Our results highlight the efficiency of human AdxR when utilizing NADPH as a flavin reducing agent. Nevertheless, akin to related flavoenzymes such as cytochrome P450 reductase, we observe that low NADPH concentrations hinder flavin reduction due to intricate equilibrium reactions between the enzyme and its substrate/product. Remarkably, the presence of MgCl2 suppresses this complex kinetic behavior by decreasing NADPH binding to oxidized AdxR, effectively transforming AdxR into a classical Michaelis-Menten enzyme. We propose that the addition of MgCl2 may be adapted for studying the reductive half-reactions of other flavoenzymes with NADPH. Furthermore, in vitro experiments provide evidence that the reduction of the yeast flavin monooxygenase Coq6p relies on an electron transfer chain comprising NADPH-AdxR-Yah1p-Coq6p, where Yah1p shuttles electrons between AdxR and Coq6p. This discovery explains the previous in vivo observation that Yah1p and the AdxR homolog, Arh1p, are required for the biosynthesis of coenzyme Q in yeast.

The effect of cigarette smoking on first-trimester crown-rump length.

Objectives: Does cigarette smoking impact the embryonic growth rate in the first trimester? Methods: This is a retrospective multicentre observational study of 2912 pregnancies. Women who presented to the early pregnancy and perinatal ultrasound units between 2010 and 2019 were included in the study. The data collected included the following: smoking status, the crown-rump length (CRL) of the pregnancy at the first ultrasound that showed an embryonic heart rate, the gestation in days and the CRL at another ultrasound up to the nuchal translucency scan and the gestation in days. Additional demographic data included the following: age, weight, height, parity and mode of delivery.Of the 2912, complete smoking and demographic data were available for 657 pregnancies. One hundred and thirty-seven (26.3%) were smokers, and 520 (73.7%) were not. The rate of change of smokers vs non-smokers between two CRLs and two different days of gestation was calculated. The Wilcoxon rank sum test with continuity correction was used for statistical analysis. Results: This gives a value of W = 31,940 and a P-value = 0.06. There is a slight shift in location for the smokers; however, it is not statistically significant. The insignificance may be due to the general large variance in growth rate. Conclusion: The impact of cigarette smoking on embryonic growth rate detected by CRL in the first trimester is statistically insignificant.

Re-evaluating the role of cerebroplacental ratio in predicting adverse perinatal outcome.

AIM: This meta-analysis evaluates the use of cerebroplacental ratio (CPR) in predicting adverse perinatal outcome. METHODS: An electronic search of PubMed, Embase, Google scholar, Cochrane Library and Up-to-Date was done using variations of 'cerebroplacental ratio' and 'cerebroumbilical ratio'. We included studies where CPR was measured and postpartum outcomes were available. Selected articles were evaluated for quality of study methodology using the Newcastle-Ottawa Scale, and aggregate statistics for relative risks, odds ratios and 95% confidence interval were calculated. RESULTS: Data from 66,392 patients in 47 studies was extracted. There were 25 prospective, 17 retrospective and 5 case-control studies. Data on each obstetric or perinatal outcome was separately analysed. When analysing the prospective data, it showed abnormal CPR can predict the need for operative delivery due to foetal distress [RR: 2.52, 95%CI: 2.10-3.02; I2 = 65.78, P < 0.001], low pH [RR: 2.19, 95%CI: 1.01-4.75; I2 = 70.26, P = 0.005] and low Apgar score [RR: 2.05, 95%CI: 1.39-3.03; I2 = 37.15, P = 0.10], foetal or neonatal demise [RR: 2.49, 95%CI: 1.00-6.20], as well as NICU admission [RR: 2.23, 95%CI: 1.84-2.70; I2 48.53, P = 0.14].The retrospective data showed a statistically significant correlation in all outcomes but the low pH. CONCLUSION: Our meta-analysis shows that CPR can be used to identify foetuses with higher risk of operative delivery due to foetal distress, low Apgar score, NICU admission, neonatal morbidity as well as stillbirth and neonatal death rates.