The production of coumarins and furanocoumarins (FCs) in higher plants is widely considered a model illustration of the adaptation of plants to their environment. In this report, we show that the multiplication of cytochrome P450 variants within the CYP71AZ subfamily has contributed to the diversification of these molecules. Multiple copies of genes encoding this enzyme family are found in Apiaceae, and their phylogenetic analysis suggests that they have different functions within these plants. CYP71AZ1 from and CYP71AZ3, 4, and 6 from were functionally characterized. While CYP71AZ3 merely hydroxylated esculetin, the other enzymes accepted both simple coumarins and FCs. Superimposing models of these enzymes led to the identification of different conformations of three regions in the enzyme active site. These sequences were subsequently utilized to mutate CYP71AZ4 to resemble CYP71AZ3. The swapping of these regions lead to significantly modified substrate specificity. Simultaneous mutations of all three regions shifted the specificity of CYP71AZ4 to that of CYP71AZ3, exclusively accepting esculetin. This approach may explain the evolution of this cytochrome P450 family regarding the appearance of FCs in parsnip and possibly in the Apiaceae.
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http://dx.doi.org/10.3389/fpls.2018.00820 | DOI Listing |
Arch Endocrinol Metab
January 2025
Unidade de Endocrinologia Ginecológica Hospital de Clínicas de Porto Alegre Divisão de Endocrinologia Porto AlegreRS Brasil Unidade de Endocrinologia Ginecológica, Divisão de Endocrinologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil.
Objective: To assess the genotypic and allelic distribution of the rs10046 polymorphism in the gene and evaluate whether this aromatase gene variant is associated with cardiovascular risk in postmenopausal women.
Materials And Methods: This cross-sectional study analyzed repository-stored samples from 370 postmenopausal women aged 44-72 years. Clinical, metabolic, and hormonal data were collected.
FEBS J
January 2025
Department of Urology, Renmin Hospital of Wuhan University, China.
In our research, we constructed models of renal ischemia-reperfusion (I/R)-exposed acute kidney injury (AKI) and unilateral ureteral obstruction (UUO)-stimulated renal fibrosis (RF) in C57BL/6 mice and HK-2 cells. We firstly authenticated that oral pinocembrin (PIN) administration obviously mitigated tissue damage and renal dysfunction induced by I/R injury, and PIN attenuated UUO-caused RF, as confirmed by the reduced expression of fibrotic markers as well as hematoxylin-eosin (H&E), Sirius red, immunohistochemistry, and Masson staining. Meanwhile, the beneficial role of PIN was again demonstrated in HK-2 cells with hypoxia-reoxygenation (H/R) or transforming growth factor beta-1 (TGF-β1) treatment.
View Article and Find Full Text PDFMol Biochem Parasitol
January 2025
Post-graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza - CE, Brazil; Fundação Oswaldo Cruz, Fiocruz, Fiocruz Ceará, Eusébio - CE, Brazil; Northeast Network of Biotechnology (RENORBIO), State University of Ceará (UECE), Fortaleza - CE, Brazil.
Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and Amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
January 2025
Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany.
In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell models and organoids, offer promising alternatives but may not fully replicate physiological processes, especially for Cytochrome P450 (CYP) families involved in extrahepatic metabolism.
View Article and Find Full Text PDFRedox Biol
January 2025
Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, South Korea; Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea. Electronic address:
Sarcopenia, the age-related decline in muscle mass and function, is a significant contributor to increased frailty and mortality in the elderly. Currently, no FDA-approved treatment exists for sarcopenia. Here, we identified norharmane (NR), a β-carboline alkaloid, as a potential therapeutic agent for mitigating muscle aging.
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