HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 28, 19327-19338, July 14, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/28/19327    most recent M512095200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, K.-Q. Articles by Wang, X.-D. Search for Related Content PubMed PubMed Citation Articles by Hu, K.-Q. Articles by Wang, X.-D. Social Bookmarking                      What's this?

The Biochemical Characterization of Ferret Carotene-9', 10'-Monooxygenase Catalyzing Cleavage of Carotenoids in Vitro and in Vivo^*

Kang-Quan Hu, Chun Liu, Hansgeorg Ernst, Norman I. Krinsky^¶, Robert M. Russell, and Xiang-Dong Wang^¶1

From the Nutrition and Cancer Biology Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, BASF, Inc., D-67056 Ludwigshafen, Germany, and the ^¶Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111

Previous studies have shown that -carotene 15,15'-monooxygenase catalyzes the cleavage of -carotene at the central carbon 15,15'-double bond but cleaves lycopene with much lower activity. However, expressing the mouse carotene 9',10'-monooxygenase (CMO2) in -carotene/lycopene-synthesizing and -accumulating Escherichia coli strains leads to both a color shift and formation of apo-10'-carotenoids, suggesting the oxidative cleavage of both carotenoids at their 9',10'-double bond. Here we provide information on the biochemical characterization of CMO2 of the ferret, a model for human carotenoid metabolism, in terms of the kinetic analysis of -carotene/lycopene cleavage into -apo-10'-carotenal/apo-10'-lycopenal in vitro and the formation of apo-10'-lycopenoids in ferrets in vivo. We demonstrate that the recombinant ferret CMO2 catalyzes the excentric cleavage of both all-trans--carotene and the 5-cis- and 13-cis-isomers of lycopene at the 9',10'-double bond but not all-trans-lycopene. The cleavage activity of ferret CMO2 was higher toward lycopene cis-isomers as compared with -carotene as substrate. Iron was an essential co-factor for the reaction. Furthermore, all-trans-lycopene supplementation in ferrets resulted in significant accumulation of cis-isomers of lycopene and the formation of apo-10'-lycopenol, as well as up-regulation of the CMO2 expression in lung tissues. In addition, in vitro incubation of apo-10'-lycopenal with the post-nuclear fraction of hepatic homogenates of ferrets resulted in the production of both apo-10'-lycopenoic acid and apo-10'-lycopenol, respectively, depending upon the presence of NAD⁺ or NADH as cofactors. Our finding of bioconversion of cis-isomers of lycopene into apo-10'-lycopenoids by CMO2 is significant because cis-isomers of lycopene are a predominant form of lycopene in mammalian tissues and apo-lycopenoids may have specific biological activities related to human health.

Received for publication, November 9, 2005 , and in revised form, May 1, 2006.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY527150.

^* This work was supported in part by Grant R01CA104932 from the National Institutes of Health and by the United States Department of Agriculture Agreement 1950-51000-064. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Human Nutrition Research Center on Aging, Tufts University, 711 Washington St., Boston, MA 02111. Tel.: 617-556-3130; Fax: 617-556-3344; E-mail: xiang-dong.wang{at}tufts.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. Sergeant, J.-J. Li, C. Fox, N. Brookbank, D. Rea, T. D. H. Bugg, and A. J. Thompson Selective Inhibition of Carotenoid Cleavage Dioxygenases: PHENOTYPIC EFFECTS ON SHOOT BRANCHING J. Biol. Chem., February 20, 2009; 284(8): 5257 - 5264. [Abstract] [Full Text] [PDF]

				V. Oberhauser, O. Voolstra, A. Bangert, J. von Lintig, and K. Vogt NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide PNAS, December 2, 2008; 105(48): 19000 - 19005. [Abstract] [Full Text] [PDF]

				B. L. Lindshield, J. L. King, A. Wyss, R. Goralczyk, C.-H. Lu, N. A. Ford, and J. W. Erdman Jr Lycopene Biodistribution Is Altered in 15,15'-Carotenoid Monooxygenase Knockout Mice J. Nutr., December 1, 2008; 138(12): 2367 - 2371. [Abstract] [Full Text] [PDF]

				S. Veeramachaneni, L. M. Ausman, S. W. Choi, R. M. Russell, and X.-D. Wang High Dose Lycopene Supplementation Increases Hepatic Cytochrome P4502E1 Protein and Inflammation in Alcohol-Fed Rats J. Nutr., July 1, 2008; 138(7): 1329 - 1335. [Abstract] [Full Text] [PDF]

				S. Hessel, A. Eichinger, A. Isken, J. Amengual, S. Hunzelmann, U. Hoeller, V. Elste, W. Hunziker, R. Goralczyk, V. Oberhauser, et al. CMO1 Deficiency Abolishes Vitamin A Production from beta-Carotene and Alters Lipid Metabolism in Mice J. Biol. Chem., November 16, 2007; 282(46): 33553 - 33561. [Abstract] [Full Text] [PDF]

				F. Lian, D. E. Smith, H. Ernst, R. M. Russell, and X.-D. Wang Apo-10'-lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo Carcinogenesis, July 1, 2007; 28(7): 1567 - 1574. [Abstract] [Full Text] [PDF]