Association of 25(OH)-Vitamin D and metabolic factors with colorectal polyps.

BACKGROUND: Studies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs. METHODS: A cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively. RESULTS: Our result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps. CONCLUSIONS: Our study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population.

The association of metabolic syndrome and its factors with gallstone disease.

BACKGROUND: To investigate the association between metabolic syndrome, including its factors, and gallstone disease (GSD) in a Taiwanese population. METHODS: We conducted a cross-sectional study during 2011 ~ 2012. A total of 12050 subjects who completed a questionnaire and underwent physical examination, laboratory tests and abdominal ultrasonography formed the study population. RESULTS: The prevalences of metabolic syndrome and gallstone disease were 24.09% and 6.16%. In an age- and sex-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease (OR = 1.61; P < 0.0001). Age, abdominal obesity, and lower high-density lipoprotein cholesterol were associated with gallstone disease after adjusting for other factors. Females had a higher odds ratio than males in waist circumference for GSD, whereas males had a lower odds ratio than females in HDL-C for GSD. CONCLUSIONS: The present study suggests that metabolic syndrome is related to gallstone disease. Waist circumference and high-density lipoprotein cholesterol are all associated with GSD. Men and women may possibly have different priorities and strategies to reduce the burden of GSD.

Controlled oxidation of aliphatic CH bonds in metallo-monooxygenases: mechanistic insights derived from studies on deuterated and fluorinated hydrocarbons.

The control over the regio- and/or stereo-selective aliphatic CH oxidation by metalloenzymes is of great interest to scientists. Typically, these enzymes invoke host-guest chemistry to sequester the substrates within the protein pockets, exploiting sizes, shapes and specific interactions such as hydrogen-bonding, electrostatic forces and/or van der Waals interactions to control the substrate specificity, regio-specificity and stereo-selectivity. Over the years, we have developed a series of deuterated and fluorinated variants of these hydrocarbon substrates as probes to gain insights into the controlled CH oxidations of hydrocarbons facilitated by these enzymes. In this review, we illustrate the application of these designed probes in the study of three monooxygenases: (i) the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath), which oxidizes straight-chain C1-C5 alkanes and alkenes to form their corresponding 2-alcohols and epoxides, respectively; (ii) the recombinant alkane hydroxylase (AlkB) from Pseudomonas putida GPo1, which oxidizes the primary CH bonds of C5-C12 linear alkanes; and (iii) the recombinant cytochrome P450 from Bacillus megaterium, which oxidizes C12-C20 fatty acids at the ω-1, ω-2 or ω-3 CH positions.

Regioselective hydroxylation of C(12)-C(15) fatty acids with fluorinated substituents by cytochrome†P450 BM3.

We demonstrate herein that wild-type cytochrome P450 BM3 can recognize non-natural substrates, such as fluorinated C12 -C15 chain-length fatty acids, and show better catalysis for their efficient conversion. Although the binding affinities for fluorinated substrates in the P450 BM3 pocket are marginally lower than those for non-fluorinated substrates, spin-shift measurements suggest that fluoro substituents at the ω-position can facilitate rearrangement of the dynamic structure of the bulk-water network within the hydrophobic pocket through a micro desolvation process to expel the water ligand of the heme iron that is present in the resting state. A lowering of the Michaelis-Menten constant (Km ), however, indicates that fluorinated fatty acids are indeed better substrates compared with their non-fluorinated counterparts. An enhancement of the turnover frequencies (kcat ) for electron transfer from NADPH to the heme iron and for CH bond oxidation by compound I (Cpd I) to yield the product suggests that the activation energies associated with going from the enzyme-substrate (ES state) to the corresponding transition state (ES(≠) state) are significantly lowered for both steps in the case of the fluorinated substrates. Delicate control of the regioselectivity by the fluorinated terminal methyl groups of the C12 -C15 fatty acids has been noted. Despite the fact that residues Arg47/Tyr51/Ser72 exert significant control over the hydroxylation of the subterminal carbon atoms toward the hydrocarbon tail, the fluorine substituent(s) at the ω-position affects the regioselective hydroxylation. For substrate hydroxylation, we have found that fluorinated lauric acids probably give a better structural fit for the heme pocket than fluorinated pentadecanoic acid, even though pentadecanoic acid is by far the best substrate among the reported fatty acids. Interestingly, 12-fluorododecanoic acid, with only one fluorine atom at the terminal methyl group, exhibits a comparable turnover frequency to that of pentadecanoic acid. Thus, fluorination of the terminal methyl group introduces additional interactions of the substrate within the hydrophobic pocket, which influence the electron transfers for both dioxygen activation and the controlled oxidation of aliphatics mediated by high-valent oxoferryl species.

Tuning the regio- and stereoselectivity of C-H activation in n-octanes by cytochrome P450 BM-3 with fluorine substituents: evidence for interactions between a C-F bond and aromatic π systems.

We employed the water-soluble cytochrome P450 BM-3 to study the activity and regiospecificity of oxidation of fluorinated n-octanes. Three mutations, A74G, F87V, and L188Q, were introduced into P450 BM-3 to allow the system to undergo n-octane oxidation. In addition, the alanine at residue 328 was replaced with a phenylalanine to introduce an aromatic residue into the hydrophobic pocket to examine whether or not van der Waals interactions between a C-F substituent in the substrate and the polarizable π system of the phenylalanine may be used to steer the positioning of the substrate within the active-site pocket of the enzyme and control the regioselectivity and stereoselectivity of hydroxylation. Interestingly, not only was the regioselectivity controlled when the fluorine substituent was judiciously positioned in the substrate, but the electron input into the iron-heme group became tightly coupled to the formation of product, essentially without abortive side reactions. Remarkable enhancement of the coupling efficiency between electron input and product formation was observed for a range of fluorinated octanes in the enzyme even without the A328F mutation, presumably because of interactions of the C-F substituent with the π system of the porphyrin macrocycle within the active-site pocket. Evidently, tightening the protein domain containing the heme pocket tunes the distribution of accessible enzyme conformations and the associated protein dynamics that activate the iron porphyrin for substrate hydroxylation to allow the reactions mediated by the high-valent Fe(IV)=O to become kinetically more commensurate with electron transfer from the flavin adenine dinucleotide (FAD)/flavin mononucleotide (FMN) reductase. These observations lend compelling evidence to support significant van der Waals interactions between the CF(2) group and aromatic π systems within the heme pocket when the fluorinated octane substrate is bound.