Lycopene

Lycopene
IUPAC name
ψ,ψ-carotene
Other names
(6E,​8E,​10E,​12E,​14E,​16E,​18E,​20E,​22E,​24E,​26E)-​2,​6,​10,​14,​19,​23,​27,​31-​octamethyldotriaconta-​2,​6,​8,​10,​12,​14,​16,​18,​20,​22,​24,​26,​30-​tridecaene
Identifiers
CAS number 502-65-8 YesY
PubChem 446925
EC number 207-949-1
Properties
Molecular formula C40H56
Molar mass 536.87 g mol−1
Appearance Deep red solid
Melting point

172–173 °C
Solubility in water Insoluble
 YesY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits & vegetables, such as red carrots, watermelons and papayas (but not strawberries or cherries). Although lycopene is chemically a carotene, it has no vitamin A activity.

In plants, algae, and other photosynthetic organisms, lycopene is an important intermediate in the biosynthesis of many carotenoids, including beta carotene, responsible for yellow, orange or red pigmentation, photosynthesis, and photo-protection. Like all carotenoids, lycopene is a polyunsaturated hydrocarbon (an unsubstituted alkene). Structurally, it is a tetraterpene assembled from eight isoprene units, composed entirely of carbon and hydrogen, and is insoluble in water. Lycopene's eleven conjugated double bonds give it its deep red color and are responsible for its antioxidant activity. Due to its strong color and non-toxicity, lycopene is a useful food coloring (registered as E160d).[1]

Lycopene is not an essential nutrient for humans, but is commonly found in the diet, mainly from dishes prepared with tomato sauce. When absorbed from the stomach, lycopene is transported in the blood by various lipoproteins and accumulates in the liver, adrenal glands, and testes.

Because preliminary research has shown an inverse correlation between consumption of tomatoes and cancer risk, lycopene has been considered a potential agent for prevention of some types of cancers, particularly prostate cancer. However, this area of research and the relationship with prostate cancer have been deemed insufficient of evidence for health claim approval by the US Food and Drug Administration (see below under Antioxidant properties and potential health benefits).

Skeletal formula of all-trans lycopene
Ball-and-stick model of all-trans lycopene

Contents

Structure and physical properties

Lycopene is a symmetrical tetraterpene assembled from 8 isoprene units. It is a member of the carotenoid family of compounds, and because it consists entirely of carbon and hydrogen, is also a carotene.[2] Isolation procedures for lycopene were first reported in 1910, and the structure of the molecule was determined by 1931. In its natural, all-trans form, the molecule is long and straight, constrained by its system of eleven conjugated double bonds. Each double bond in this extended π electron system reduces the energy required for electrons to transition to higher energy states, allowing the molecule to absorb visible light of progressively longer wavelengths. Lycopene absorbs all but the longest wavelengths of visible light, so it appears red.[3]

Plants and photosynthetic bacteria naturally produce all-trans lycopene, but a total of 72 geometric isomers of the molecule are sterically possible.[4] When exposed to light or heat, lycopene can undergo isomerization to any of a number of these cis-isomers, which have a bent rather than linear shape. Different isomeres were shown to have different stabilities due to their molecular energy (highest stability: 5-cis ≥ all-trans ≥ 9-cis ≥ 13-cis > 15-cis > 7-cis > 11-cis: lowest).[5] In the human bloodstream, various cis-isomers constitute more than 60% of the total lycopene concentration, but the biological effects of individual isomers have not been investigated.[6]

Lycopene is insoluble in water, and can be dissolved only in organic solvents and oils. Because of its non-polarity, lycopene in food preparations will stain any sufficiently porous material, including most plastics. While a tomato stain can be fairly easily removed from fabric (provided the stain is fresh), lycopene diffuses into plastic, making it impossible to remove with hot water or detergent. If lycopene is oxidized (for example, by reacting with bleaches or acids), the double bonds between the carbon atoms will be broken; cleaving the molecule, breaking the conjugated double bond system, and eliminating the chromophore.

Role in photosynthesis

Lycopene is a key intermediate in the biosynthesis of many carotenoids.

Carotenoids like lycopene are important pigments found in photosynthetic pigment-protein complexes in plants, photosynthetic bacteria, fungi, and algae. They are responsible for the bright colors of fruits and vegetables, perform various functions in photosynthesis, and protect photosynthetic organisms from excessive light damage. Lycopene is a key intermediate in the biosynthesis of many important carotenoids, such as beta-carotene, and xanthophylls.

Biosynthesis

The biosynthesis of lycopene in eukaryotic plants and in prokaryotic cyanobacteria is similar, as are the enzymes involved.[7] Synthesis begins with mevalonic acid, which is converted into dimethylallyl pyrophosphate. This is then condensed with three molecules of isopentenyl pyrophosphate (an isomer of dimethylallyl pyrophosphate), to give the twenty carbon geranylgeranyl pyrophosphate. Two molecules of this product are then condensed in a tail-to-tail configuration to give the forty carbon phytoene, the first committed step in carotenoid biosynthesis. Through several desaturation steps, phytoene is converted into lycopene. The two terminal isoprene groups of lycopene can be cyclized to produce beta carotene, which can then be transformed into a wide variety of xanthophylls.[8]

Dietary sources

Dietary sources of lycopene[9]
Source μg/g wet weight
Gac 2,000–2,300
Raw tomato 8.8–42
Tomato juice 86–100
Tomato sauce 63–131
Tomato ketchup 124
Watermelon 23–72
Pink grapefruit 3.6–34
Pink guava 54
Papaya 20–53
Rosehip puree 7.8
Apricot < 0.1

Fruits and vegetables that are high in lycopene include gac, tomatoes, watermelon, pink grapefruit, pink guava, papaya, red bell pepper, seabuckthorn, wolfberry (goji, a berry relative of tomato), and rosehip. Although gac (Momordica cochinchinensis Spreng) has the highest content of lycopene of any known fruit or vegetable, up to 70 times more than tomatoes for example[10], due to gac's rarity outside its native region of southeast Asia, tomatoes and tomato-based sauces, juices, and ketchup account for more than 85% of the dietary intake of lycopene for most people.[11] The lycopene content of tomatoes depends on species and increases as the fruit ripens.[12]

Unlike other fruits and vegetables, where nutritional content such as vitamin C is diminished upon cooking, processing of tomatoes increases the concentration of bioavailable lycopene. Lycopene in tomato paste is four times more bioavailable than in fresh tomatoes. For this reason, tomato sauce is a preferable source as opposed to raw tomatoes.

While most green leafy vegetables and other sources of lycopene are low in fats and oils, lycopene is insoluble in water and is tightly bound to vegetable fiber. Processed tomato products such as pasteurized tomato juice, soup, sauce, and ketchup contain the highest concentrations of bioavailable lycopene from tomato-based sources.

Cooking and crushing tomatoes (as in the canning process) and serving in oil-rich dishes (such as spaghetti sauce or pizza) greatly increases assimilation from the digestive tract into the bloodstream. Lycopene is fat-soluble, so the oil is said to help absorption. Gac is a notable exception, containing high concentrations of lycopene and also saturated and unsaturated fatty acids.[13]

Lycopene may be obtained from vegetables and fruits such as the tomato, but another source of lycopene is the fungus Blakeslea trispora. Gac is a promising commercial source of lycopene for the purposes of extraction and purification.

The cis-lycopene from some varieties of tomato is more bioavailable.[14]

Pharmacokinetics

Distribution of lycopene[15]
Tissue nmol/g wet weight
Liver 1.28–5.72
Kidney 0.15–0.62
Adrenal 1.9–21.6
Testes 4.34–21.4
Ovary 0.25–0.28
Adipose 0.2–1.3
Lung 0.22–0.57
Colon 0.31
Breast 0.78
Skin 0.42

After ingestion, lycopene is incorporated into lipid micelles in the small intestine. These micelles are formed from dietary fats and bile acids, and help to solubilize the hydrophobic lycopene and allow it to permeate the intestinal mucosal cells by a passive transport mechanism. Little is known about the liver metabolism of lycopene, but like other carotenoids, lycopene is incorporated into chylomicrons and released into the lymphatic system. In blood plasma, lycopene is eventually distributed into the very low and low density lipoprotein fractions.[16] Lycopene is mainly distributed to fatty tissues and organs such as the adrenal glands, liver, and testes.

Adverse effects

Lycopene is non-toxic and is commonly found in the diet, but cases of excessive carotenoid intake have been reported. In a middle aged woman who had prolonged and excessive consumption of tomato juice, her skin and liver were colored orange-yellow and she had elevated levels of lycopene in her blood. After three weeks on a lycopene-free diet her skin color returned to normal.[16] This discoloration of the skin is known as lycopenodermia[17] and is non-toxic.

Antioxidant properties and potential health benefits

Lycopene may be the most powerful carotenoid quencher of singlet oxygen[18], being 100 times more efficient in test tube studies of singlet-oxygen quenching action than vitamin E, which in turn has 125 times the quenching action of glutathione (water soluble). Singlet oxygen produced during exposure to ultraviolet light is a primary cause of skin aging.[19]

Given its antioxidant properties, substantial scientific and clinical research has been devoted to a possible correlation between lycopene consumption and general health. Early research suggested some amelioration of cardiovascular disease, cancer, diabetes, osteoporosis, and even male infertility.[20]

There have been several studies produced that analyze the anti-cancer properties of lycopene, although research has been primarily inconclusive. Evidence for lycopene’s benefit was strongest for cancers of the lung, stomach, and prostate gland. Lycopene is not modified to vitamin A in the body so can be accessible for other benefits such as antioxidation. The absence of the beta-ionone ring structure for lycopene increases its antioxidant action. Lycopene is also the most efficient oxygen and free radicals quencher and is the prime carotenoid in plasma and other tissues. Lycopene is also found in lung tissue and is valuable in protecting lymphocytes from NO2 damage found in lung cancer. Lycopene also may help decrease the impact of oxidative load from pylori infections in the stomach. The tomato-derived carotenoid lycopene may reduce risk of cancer by activating special cancer preventive enzymes such as phase II detoxification enzymes, which remove harmful carcinogens from cells and the body[21]. In one study of lycopene as a inhibitor of human cancer cell proliferation, it was found that unlike cancer cells, human fibroblasts were less sensitive to lycopene, and the cells gradually escaped growth inhibition over time. In addition to its inhibitory effect on basal endometrial cancer cell proliferation, lycopene also was found to suppress insulin-like growth factor-I-stimulated growth. Insulin-like growth factors are major autocrine/paracrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrine/paracrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors[22]. In different studies however, lycopene was even found to have an inhibitory effect on cataract development[23] and several different kinds of cancer cells including breast and endometrial cancer cells[24], prostrate carcinoma cells[25], and colon cancer cells[26].

After extensive review reported in November 2005, the United States Food and Drug Administration has cast significant doubt on the potential for lowering disease risk, showing no link between lycopene and prevention of prostate cancer, although it is suggestive that eating whole tomatoes does provide benefit, perhaps because as yet undiscovered compounds (other than lycopene) are the beneficial agents.[27] The FDA review permitted a highly limited qualified claim to be used for tomatoes and tomato products which contain lycopene, as a guide that would not mislead consumers, namely:

Very limited and preliminary scientific research suggests that eating one-half to one cup of tomatoes and/or tomato sauce a week may reduce the risk of prostate cancer. FDA concludes that there is little scientific evidence supporting this claim.

The related carotenoid antioxidant, beta-carotene, has been shown to increase the number of prostate cancer cases in a subset of patients,[28] although this area of research remains controversial and ongoing.

See also

Notes and references

Notes

  1. ↑ 21 CFR 73.585
  2. ↑ Grossman et al. (2004) p. 129
  3. ↑ Rao et al. (2007) p. 210
  4. ↑ 1054 isomers are theoretically possible, but only 72 are possible due to steric hinderance. IARC Handbook, (1998) p. 25
  5. ↑ Chasse et al. Journal of Molecular Structure: THEOCHEM, Volume 571, Number 1, 27 August 2001 , pp. 27-37(11)[1]
  6. ↑ Lycopene: Its role in human health and disease, Rao 'et al.', AGROFood industry hi-tech, July/August 2003 [2]
  7. ↑ Cunningham (2007) p. 533
  8. ↑ Armstrong (1996) p. 229
  9. ↑ Rao and Rao (2007) pp. 209–210
  10. ↑ USDA study on Cartenoid content of gac fruit
  11. ↑ Rao (2007) p.
  12. ↑ Khan et al. (2008) p. 495
  13. ↑ Ishida BK, Turner C, Chapman MH, McKeon TA (January 2004). "Fatty acid and carotenoid composition of gac (Momordica cochinchinensis Spreng) fruit". Journal of Agricultural and Food Chemistry 52 (2): 274–9. doi:10.1021/jf030616i. PMID 14733508. 
  14. ↑ http://www.medicalnewstoday.com/articles/64157.php
  15. ↑ Stahl (1996) p. 7
  16. ↑ 16.0 16.1 Stahl (1996) p. 6
  17. ↑ Institute of Medicine, Food and Nutrition Board. Beta-carotene and other carotenoids. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 2000:325-400.
  18. ↑ Di Mascio (1989) pp. 532–538
  19. ↑ Berneburg (1999) pp. 15345–15349
  20. ↑ Giovannucci (1995) pp. 1767–76
  21. ↑ Giovannucci et al.(2002) p.391-398
  22. ↑ Levy et al. (1995) p.257-266
  23. ↑ Pollack et al. (1997) p.31-36
  24. ↑ Nahum et al.(2001) p.3428-3436
  25. ↑ Giovannucci et al.(2002) p.391-398
  26. ↑ Narisawa et al. (1996) p.137-142
  27. ↑ Qualified Health Claims: Letter Regarding Tomatoes and Prostate Cancer(Lycopene Heath Claim Coalition)(Docket No. 2004Q-0201) US FDA/CFSAN November 2005 [3]
  28. ↑ American Association for Cancer Research (May 17, 2007). "No Magic Tomato? Study Breaks Link between Lycopene and Prostate Cancer Prevention". Science Daily. http://www.sciencedaily.com/releases/2007/05/070517063011.htm. 

References

External links

Carotenoids
Carotenes (C40)
α-Carotene · β-Carotene · γ-Carotene · δ-Carotene · ε-Carotene · ζ-Carotene · Lycopene · Neurosporene · Phytoene · Phytofluene
Xanthophylls (C40)
Antheraxanthin · Astaxanthin · Canthaxanthin · Citranaxanthin · Cryptoxanthin · Diadinoxanthin · Diatoxanthin · Dinoxanthin · Flavoxanthin · Fucoxanthin · Lutein · Neoxanthin · Rhodoxanthin · Rubixanthin · Violaxanthin · Zeaxanthin
Apocarotenoids (C<40)
Abscisic acid · Apocarotenal · Bixin · Crocetin · Food orange 7 · Ionones · Peridinin
Vitamin A retinoids (C20)
Retinal · Retinoic acid · Retinol
Retinoid drugs
Acitretin · Alitretinoin · Bexarotene · Etretinate · Fenretinide · Isotretinoin · Tazarotene · Tretinoin