Carotenoids regulation

The hypothesis that polar carotenoids regulate membrane fluidity of prokaryotes (performing a function similar to cholesterol in eukaryotes) was postulated by Rohmer et al. (1979). Thus, the effects of polar carotenoids on membrane properties should be similar in many ways to the effects caused by cholesterol. These similarities were demonstrated using different EPR spin-labeling approaches in which the effects of dipolar, terminally dihydroxylated carotenoids such as lutein,... 

Many carotenoids function in humans as vitamin A precursors however, not all carotenoids have provitamin A activity (Table 3). Of the biologically active carotenoids, -carotene has the greatest activity. Despite the fact that theoretically one molecule of -carotene is a biological source of two molecules of vitamin A, this relationship is not observed and 6 p.g -carotene is equivalent to 1 p. vitamin A. Although -carotene and vitamin A have complementary activities, they caimot totally replace each other. Because the conversion of -carotene to vitamin A is highly regulated, toxic quantities of vitamin A cannot accumulate and -carotene can be considered as a safe form of vitamin A (8). 

Since carotenoids are derived for the central isoprenoid pathway (Fig. 13.3), the regulation of their formation must involve a co-ordinated flux of isoprenoid imits into this branch of the pathway as well as into others such as the biosynthesis of sterols, gibberellins, phytol and terpenoid quinones. An imderstanding of the complexities of regulation of the pathway is necessary in order to target the regulatory steps for genetic manipulation. 

Carotenoid accumulation during fruit ripening in tomato has been studied extensively and is a good model system to elucidate the regulation of the process. During ripening the concentration of carotenoids increases between 10 and 15-fold due mainly to a 500-fold increase in the concentration of lycopene (Fraser et al, 1994 Table 13.5). Accumulation of lycopene begins... 

Clearly, the control of gene expression at the transcriptional level is a key regulatory mechanism controlling carotenogenesis in vivo. However, post-transcriptional regulation of carotenoid biosynthesis enzymes has been found in chromoplasts of the daffodil. The enzymes phytoene synthase (PSY) and phytoene desaturase (PDS) are inactive in the soluble fraction of the plastid, but are active when membrane-bound (Al-Babili et al, 1996 Schledz et al, 1996). The presence of inactive proteins indicates that a post-translational regulation mechanism is present and is linked to the redox state of the membrane-bound electron acceptors. In addition, substrate specificity of the P- and e-lycopene cyclases may control the proportions of the p, P and P, e carotenoids in plants (Cunningham et al, 1996). 

The carotenoid pathway may also be regulated by feedback inhibition from the end products. Inhibition of lycopene cyclisation in leaves of tomato causes increase in the expression of Pds and Psy-1 (Giuliano et al, 1993 Corona et al, 1996). This hypothesis is supported by other studies using carotenoid biosynthesis inhibitors where treated photosynthetic tissues accumulated higher concentrations of carotenoids than untreated tissues (reviewed by Bramley, 1993). The mechanism of this regulation is unknown. A contrary view, however, comes from studies on the phytoene-accumulating immutans mutant of Arabidopsis, where there is no feedback inhibition of phytoene desaturase gene expression (Wetzel and Rodermel, 1998). 

BOUVIER F, D HARLINGUE A, HUGUENEY P, MARIN E, MARION-POLL A and CAMARA B (1996) Xanthophyll biosynthesis cloning, expression, functional reconstitution and regulation of 3-cyclohexenyl carotenoid epoxidase from pepper Capsicum annuum) , J Biol Chem, 271, 28861-7. 

BRAMLEY p M (1997) The regulation and genetic manipulation of carotenoid biosynthesis in tomato fruit , PureAppl Chem, 69, 2159-62. 

BRAMLEY p M (2002) Regulation of carotenoid formation during tomato fruit ripening and... 

GiuLiANO G (1996) Regulation of a carotenoid biosynthesis gene promoter during plant development , Plant J, 9, 505-12. 

GiuLiANO G, BARTLEY G E and scoLNiK p A (1993) Regulation of carotenoid biosynthesis during tomato fruit development . Plant Cell, 5, 379-87. 

RONEN G, COHEN M, ZAMIR D and HIRSCHBERG J (1999) Regnlation of carotenoid biosynthesis during tomato fruit development expression of the gene for lycopene epsilon cyclase is down regulated during ripening and is elevated in the mutant delta . Plant J, 17, 341-51. 

Caco-2 cells and ezetimibe, a potent inhibitor of chloresterol absorption in humans, it was reported that (1) carotenoid transport was inhibited by ezetimibe up to 50% and the extent of that inhibition diminished with increasing polarity of the carotenoid molecule, (2) the inhibitory effects of ezetimibe and the antibody against SR-BI on P-carotene transport were additive, and (3) ezetimibe may interact physically with cholesterol transporters as previously suggested - and also down-regulate the gene expression of three surface receptors, SR-BI, NPCILI, and ABCAl. 

During, A., Dawson, H.D., and Harrison, E.H., Carotenoid transport is decreased and expression of the lipid transporters SR-Bl, NPCILI, and ABCAl is down-regulated in Caco-2 cells treated with ezetimibe, J. Nutr., 135, 2305, 2005. 

In the natural world, carotenoid oxidation products are important mediators presenting different properties. Volatile carotenoid-derived compounds such as noriso-prenoids are well known for their aroma properties. Examples include the cyclic norisoprenoid P-ionone and the non-cyclic pseudoionone or Neral. Carotenoid oxidation products are also important bioactive mediators for plant development, the best-known example being abscisic acid. Apo-carotenoids act as visual and volatile signals to attract pollination and seed dispersal agents in the same way as carotenoids do, but they are also plant defense factors and signaling molecules for the regulation of plant architecture. 

Cunningham, F.X., Regulation of carotenoid synthesis and accumulation in plants. Pure Appl. Chem. 74, 1409, 2002. 

Boteha-Pavia, P. et al.. Regulation of carotenoid biosynthesis in plants evidence for a key role of hydroxymethylbutenyl diphosphate reductase in controhing the supply of plastidial isoprenoid precursors. Plant J. 40, 188, 2004. 

Natural (3-carotene contains numerous carotenoids and essential nutrients that are not present in synthetic (3-carotene. Natural (3-carotene can be consumed in larger quantities because body tissues regulate its use. Natural sources generally contain one or two carotenoids in lower concentrations and thus may not be suitable for all applications. However Dunaliella contains a range of carotenoids with wider applications. 

This pigment is recognized by the U.S. Food and Drug Administration (21 Code of Federal Regulations, Part 73) as a color additive exempted from certification (Subpart A, Foods, Section 73.35, Astaxanthin). Formulations containing astaxanthin include soft gelatin capsules containing 100 mg equivalents of total carotenoids, a skin care... 

Huang, L. and A. Haug. 1974. Regulation of membrane lipid fluidity in Acholeplasma laidlawii Effect of carotenoid pigment content. Biochim. Biophys. Acta 352 361-370. 

Hix LM, Lockwood SF, and Bertram JS. 2004. Bioactive carotenoids Potent antioxidants and regulators of gene expression. Redox Report 9 181-191. 

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