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Author Mein, Jonathan R
Title Metabolic Pathways of Carotenoid Metabolism: Insights into the Biochemical and Regulatory Pathways of Carotenoid Cleavage
book jacket
Descript 207 p
Note Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page:
Adviser: Xiang-Dong Wang
Thesis (Ph.D.)--Tufts University, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, 2011
Consumption of a diet high in carotenoid-rich fruits and vegetables is strongly associated with a decreased risk of many chronic and degenerative diseases. Carotenoids are a class of lipophilic compounds found in many fruits and vegetables and have often been targeted as imparting some of the beneficial effects associated with fruit and vegetable consumption. However, our understanding of the biochemical and molecular framework of carotenoid metabolism is incomplete. Investigating the biochemical and molecular pathways of carotenoid metabolism are important to understanding their biological functions
Carotene-15,15'-monooxygenase (CMO1) is involved in vitamin A formation, while recent studies suggest that carotene-9',10'-monooxygenase (CMO2) may have a broader substrate specificity than previously recognized. The first part of this research investigated the in vitro cleavage activity of recombinant ferret CMO2 towards the xanthophylls lutein, zeaxanthin and beta-cryptoxanthin. Utilizing HPLC, LC-MS and GCMS, we identified both volatile and non-volatile apocarotenoid products including 3-OH-beta-ionone, 3-OH-alpha-ionone, beta-ionone, 3-OH-alpha-apo-10'-carotenal, 3-OH-beta-apo-10'-carotenal, and beta-apo-10'-carotenal, indicating cleavage at both the 9,10 and 9',10' carbon-carbon double bond. Kinetic analysis indicated the xanthophylls zeaxanthin and lutein are preferentially cleaved over beta-cryptoxanthin, indicating a key role of CMO2 in non-provitamin A carotenoid metabolism. Furthermore, incubation of 3-OH-beta-apo-10'-carotenal with CMO2 lysate resulted in the formation of 3-OH-beta-ionone. In the presence of NAD+, in vitro incubation of 3-OH-beta-apo-10'-carotenal with ferret hepatic homogenates resulted in the formation of 3-OH-beta-apo-10'-carotenoic acid. Since apocarotenoids serve as important signaling molecules in a variety of biological processes, enzymatic cleavage of xanthophylls by mammalian CMO2 represents a potential new avenue of investigation regarding vertebrate carotenoid metabolism and biological function
Several well-implemented cohort studies have shown blood levels and dietary intake of beta-cryptoxanthin to be strongly associated with a decreased risk of lung cancer independent of vitamin A. The objective of this study was to assess the regulation of CMO1 and CMO2 expression in selected ferret tissues in response to varying doses of beta-cryptoxanthin supplementation. We first partially cloned the ferret CMO1 gene and compared the relative abundance of CMO1 and CMO2 expression in various tissues. Tissue-specific comparisons revealed significant differences in expression levels of CMO1 and CMO2. CMO1 expression was significantly higher in the intestinal mucosa while CMO2 expression was significantly higher in the lungs, visceral adipose and kidneys compared to CMO1. Low-dose (7.5 mug/kg body weight per day) and high-dose (37.5 mug/kg body weight per day) beta-cryptoxanthin supplementation for 9 weeks resulted in a dose-dependent increase in beta-cryptoxanthin concentrations with no changes in retinyl palmitate selected tissues. There was a significant decrease in lung CMO2 expression in both low- and high-dose supplementation groups with little changes in CMO1 or CMO2 expression in other tissues. The relative abundance of CMO2 expression in the lungs and down-regulation by beta-cryptoxanthin supplementation indicates a potential role of CMO2 in the biological activity of beta-cryptoxanthin in human health
School code: 1546
Host Item Dissertation Abstracts International 72-06B
Subject Chemistry, Biochemistry
Health Sciences, Nutrition
Alt Author Tufts University, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy. Biochemical and Molecular Nutrition
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