Carotene 15,15’-dioxygenase

As discussed in Section 2.2.2.2, only a relatively small proportion of carotene undergoes oxidation in the intestinal mucosa, and a significant amount of carotene enters the circulation in chylomicrons. Novotny and coworkers (1995) reported a study in one subject given an oral dose of pff]/3-carotene dissolved in oU 22% was absorbed - 17.8% as carotene and 4.2% as retinoids. Their results suggest that nonintestinal carotene dioxygenase is important in retinoid formation, because there was a late disappearance of labeled carotene from the circulation and the appearance of labeled retinoids. 

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In nature, vitamin A aldehyde is produced by the oxidative cleavage of P-carotene by 15,15 - P-carotene dioxygenase. Alternatively, retinal is produced by oxidative cleavage of P-carotene to P-apo-S -carotenal followed by cleavage at the 15,15 -double bond to vitamin A aldehyde (47). Carotenoid biosynthesis and fermentation have been extensively studied both ia academic as well as ia iadustrial laboratories. On the commercial side, the focus of these iavestigations has been to iacrease fermentation titers by both classical and recombinant means. 

Figure 45-1. P-Carotene and the major vitamin A vitamers. Shows the site of cleavage of P-carotene into two molecules of retinaldehyde by carotene dioxygenase.

Figure 2.3. Oxidative cleavage of j6-carotene by carotene dioxygenase (EC 1.14.99.36), and onward metabolism of retinaldehyde catalyzed by retinol dehydrogenase (EC 1.1.1.105) and retinaldehyde oxidase (EC 1.2.3.11).

Carotene Dioxygenase As shown in Figure 2.3,/S-carotene and other provitamin A carotenoids undergo oxidative cleavage to retinaldehyde... 

Other carotenoids in the diet, which are not substrates, such as canthaxan-thin and zeaxanthin, may inhibit carotene dioxygenase and reduce the proportion that is converted to retinol (Grolier et al., 1997). Similarly, a variety of antioxidants that occur in foods together with carotenoids, including flavo-noids (Section 14.7.2), also inhibit carotene dioxygenase. 

A number of studies have reported low semm concentrations of retinol and high concentrations of /3-carotene in patients with insulin-dependent diabetes mellitus. Krill and coworkers (1997) showed that up to one-third of nondiabetic first-degree relatives of patients with diabetes also showed a low serum retinokcarotene ratio, implying a genetic predisposition to low activity of carotene dioxygenase, possibly associated with insulin-dependent diabetes. 

The Reaction Specificity of Carotene Dioxygenase Whereasthe principal site of carotene dioxygenase attack is the 15,15 -central bond of p-carotene, there is evidence that asymmetric cleavage also occurs, leading to formation of 8 -, 10 -, and 12 -apo-carotenals, as shown in Figure 2.4. These apo-carotenals are metabolized by oxidation to apo-carotenoic acids, which are substrates for /3-oxidation to retinoic acid and a number of other metabolites. 

Grolier P, Duszka C, Borel P, Alexandre-Gouabau MC, and Azais-Braesco V (1997) In vitro and in vivo inhibition of heta-carotene dioxygenase activity by canthaxanthin in rat intestine. Archives of Biochemistry and Biophysics 348,233-8. 

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