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J Nutr. 2004 Jan;134(1):241S-245S.

Alpha and omega of carotenoid cleavage.

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  • Lipid Research Laboratory, VA Medical Center and the George Washington University, Washington, DC, USA. Raj.lakshman@med.va.gov

Abstract

In early 1900s, based on indirect evidence, Steenbock and Morton independently predicted that beta-carotene could be the biological precursor of vitamin A, although this notion was contested by others. In the 1930s, Thomas Moore showed the in vivo formation of vitamin A from beta-carotene. But it was not until Jim Olson and DeWitt Goodman independently showed in 1965 the formation of retinal, the aldehyde form of vitamin A from beta-carotene in cell-free extracts of liver and intestine, that this vital pathway of beta-carotene was recognized. Despite compelling evidence in several experimental systems for the central cleavage of beta-carotene to retinal by many investigators, there were some careful independent studies by Glover et al., Ganguly et al., Hansen and Meret and Krinsky et al. showing the eccentric cleavage of beta-carotene resulting in the formation of apocarotenoids both in vivo and in vitro. In an attempt to resolve this controversial issue, we revisited this problem in 1989 and showed beyond doubt the formation of retinal as the sole enzymatic product of a cytosolic enzyme from rabbit and rat intestinal mucosa by mass spectrometry and tracer analysis of the crystallized product. This was confirmed in 1996 by Nagao using the pig intestinal extract. Yeum et al. confirmed in 2000 that retinal is the sole product of beta-carotene cleavage in the presence of alpha-tocopherol, and that the observed formation of apocarotenoids occurs only in the absence of an antioxidant like alpha-tocopherol. In the same year, Barua and Olson also concluded from their in vivo studies in rats that central cleavage is by far the major pathway for the formation of vitamin A from beta-carotene. Beta, beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) is the key enzyme that cleaves beta-carotene into two molecules of retinal. It is a cytosolic enzyme primarily localized in the duodenal mucosa although it has been found in liver. It is a 66 kDa sulfhydryl protein, requires molecular oxygen and is activated by ferrous ions. It is highly specific for 15:15' ethylenic bond of carotenoids although it has fairly broad specificity towards a number of carotenoids with at least one intact beta-ionone ring. The dioxygenase was recently cloned from Drosophila melanogaster and from the chicken intestine. The recombinant protein was found to form retinal as the sole cleavage product of beta-carotene. No apo-carotenoids were formed. Therefore, it is unequivocally proven that the major, if not the sole, pathway of beta-carotene cleavage to vitamin A is by oxidative cleavage of the central ethylenic bond of beta-carotene to yield two molecules of retinal. Most recently, human dioxygenase has also been cloned. Thus, the wisdom, vision and epoch-making mission of Jim Olson in the science of beta-carotene metabolism have been accomplished. I have no doubt that the impact of his original discovery of the dioxygenase and its importance in vitamin A nutriture should be forthcoming in the near future.

PMID:
14704327
[PubMed - indexed for MEDLINE]
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