Retinol 8-carotene

Manzi, P., Panfili, G., and Pizzoferrato, L. 1996. Normal and reversed-phase HPLC for more complete evaluation of tocopherols, retinols, carotenes and sterols in dairy products. Chroma-tographia 43 89-93. 

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

Preformed vitamin A is found only in tmimtils and a smedl number of bacteria. A number of the carotenoid pigments in plemts can be cleaved oxidatively to yield retinol / -carotene is quantitatively the most important of these provitamin A ctu otenoids. Although preformed retinol is both acutely and chronically toxic in excess, carotene is not, because there is only a limited capacity to cleave it to retinol. 

Cheese type Retinol Carotene (Mg) Vitamin D (Mg) Vitamin E (mg) Thiamine (mg) Riboflavin (mg) Niacin (mg) Vitamin Bf> (mg) Vitamin B,2 (Mg) Folate (me) Pantothenate (mg) Biotin (Mg)... 

Carotenoids absorb visible light (Section 13 21) and dissipate its energy as heat thereby protecting the organism from any potentially harmful effects associated with sunlight induced photochemistry They are also indirectly involved m the chemistry of vision owing to the fact that p carotene is the biosynthetic precursor of vitamin A also known as retinol a key substance m the visual process... 

Ref. 2. Vitamin A is reported as retinol [68-26-8] equivalents/L. RE = 1 /ig of all trans-i.etSio 6 )lg of all /ra j -(3-carotene, and 12 )lg of other provitamin A cartenoids, with older definitions giving 3.33 lU vitamin A from retinol and 10 lU vitamin A activity from -carotene. 

The stmcture of vitamin A [11103-57-4] and some of the important derivatives are shown in Figure 1. The parent stmcture is aH-Zra/ j -retinol [68-26-8] and its lUPAC name is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol (1). The numbering system for vitamin A derivatives parallels the system used for the carotenoids. In older Hterature, vitamin A compounds are named as derivatives of trimethyl cyclohexene and the side chain is named as a substituent. For retinoic acid derivatives, the carboxyl group is denoted as C-1 and the trimethyl cyclohexane ring as a substituent on C-9. The stmctures of vitamin A and -carotene were elucidated by Karrer in 1930 and several derivatives of the vitamin were prepared by this group (5,6). In 1935, Wald isolated a substance found in the visual pigments of the eye and was able to show that this material was identical with Karrer s retinaldehyde [116-31-4] (5) (7). 

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

Property Retinol Retinyl acetate Retinyl palmitate Retinyl propionate o p-carotene... 

In the BASF synthesis, a Wittig reaction between two moles of phosphonium salt (vitamin A intermediate (24)) and C q dialdehyde (48) is the important synthetic step (9,28,29). Thermal isomerization affords all /ra/ j -P-carotene (Fig. 11). In an alternative preparation by Roche, vitamin A process streams can be used and in this scheme, retinol is carefully oxidized to retinal, and a second portion is converted to the C2Q phosphonium salt (49). These two halves are united using standard Wittig chemistry (8) (Fig. 12). 

The known beneficial effects of retinoids on malignancies are assumed to relate to retinoid receptor-mediated antipromoting and anti-initiating effects. The latter appeals to be influenced by interference of several xenobiotics with different steps of the retinoid metabolism in the target cell. Of the carotenoids, (3-carotene is the most potent retinol precursor, yet being... 

A Retinol, p-carotene Visual pigments in the retina regulation of gene expression and cell differentiation p-carotene is an antioxidant Night blindness, xerophthalmia keratinization of skin... 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

ATBC = Alpha Tocopherol Beta Carotene Prevention Study CARET = The Beta Carotene and Retinol Efficacy Trial PHYS = Physicians Health Study. 

Subsequent studies have confirmed that the reason for this discrepancy is that the rat is able to rapidly metabolise P-carotene to retinol in the intestine, through the action of intestinal dioxygenase. In contrast humans absorb P-carotene systemically such that plasma levels of P-carotene increase to levels not found in the rodent. A more appropriate animal model is the ferret, which shows a similar metabolism to humans. High levels of plasma P-carotene in the ferret induce the cellular transcription factors c-fos and c-jun, and squamous metaplasia is seen in the lung with or without exposure to cigarette smoke (SCF, 2000). Even after the investment of all these resources it has not been possible for the EU Scientific Committee on Food to set an ADI. 

OMENN G s, GOODMAN G E, THORNQUIST M, et al., (1996) Risk factors for limg cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst. 88 1550-59. 

The carotenoids are the most widely distributed group of pigments, occur naturally in large quantities, and are known for their structural diversity and various functions. The carotenoids constitnte a widespread class of natural pigments that occur in all three domains of life in the eubacteria, the archea, and the eucarya. Carotenoids are ubiquitous organic molecules, but they are not produced by the human body. They have been fonnd to be essential to human health based on the nutritional understanding of vitamin A (retinol) and (i-carotene. ... 

It is assumed that in order to have vitamin A activity a molecule must have essentially one-half of its structure similar to that of (i-carotene with an added molecule of water at the end of the lateral polyene chain. Thus, P-carotene is a potent provitamin A to which 100% activity is assigned. An unsubstituted p ring with a Cii polyene chain is the minimum requirement for vitamin A activity. y-Car-otene, a-carotene, P-cryptoxanthin, a-cryptoxanthin, and P-carotene-5,6-epoxide aU have single unsubstimted rings. Recently it has been shown that astaxanthin can be converted to zeaxanthin in trout if the fish has sufficient vitamin A. Vitiated astaxanthin was converted to retinol in strips of duodenum or inverted sacks of trout intestines. Astaxanthin, canthaxanthin, and zeaxanthin can be converted to vitamin A and A2 in guppies. ... 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

Holick, C.N. et al., Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study, Am. J. Epidemiol., 156, 536, 2002. 

Mafila, N. et al.. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers, Eur. J. Clin. Nutr, 56, 615, 2002. 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Novotny, J.A. et al.. Plasma appearance of labeled -carotene, lutein, and retinol in humans after consumption of isotopicaUy labeled kale, J. Lipid Res., 46, 1896, 2005. 

De Pee, S. et al.. Orange fruit is more effective than are dark-green, leafy vegetables in increasing serum concentrations of retinol and (3-carotene in school children in Indonesia, Am. J. Clin. Nutr, 68, 1058, 1998. 

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