glucosinolates Flashcards
Important compounds include:
glucosinolates isothiocyanates indoles dithiolthiones other compounds: carotenoids vitamin C flavonoids
Sinalbin, Sinigrin, Progoitrin
Pungent/bitter glucosinolates in horseradish, mustards, brussel sprouts
Goitrin – can interfere with thyroid iodine uptake
- low levels in eg. broccoli - problem for livestock fed rapeseed meal
Conversion of glucosinolates to isothiocyanates by
plant myrosinase.
Isothiocyanates
3 compounds
Compounds include: Penethyl isothiocyanate Sulforaphane Allyl isothiocyanate Inhibit or block tumours induced by chemical carcinogens (e.g. mammary, lung)
Mechanism(s)
Inhibit Phase I enzymes (cytochrome P450 1A1)
Potent inducers of Phase II enzymes
phase 1 enzymes
Phase 1 enzymes
Cytochrome P450
add a hydroxyl group- kind of activate the toxin, helps phase 2 enzymes attach
Phase 2 enzymes
Phase 2 enzymes Reduce quinones Reduce aldehydes Synthesize glutathione Conjugate glutathione Conjugate glucuronic acid make tham more water soluble
Classical = drug metabolizing enzymes
- glutathione S-transferase, glucuronidase, sulfatase, NAD(P)H:quinone oxidoreductase
Now – include antioxidant enzymes under control of antioxidant response element (ARE)
- catalase, GSH peroxidase, CuZn superoxide dismutase, glutathione synthase
Reversible reaction of sulforaphane with Keap1 cysteine sulfhydryl groups. The asterisk indicates the isothiocyanate electrophilic carbon.
How phytochemicals reduce cancer risk
Antioxidants
Prevent inflammation
Inactivate/modulate enzyme systems (Phase 1) that produce carcinogens, and induce enzyme systems (Phase 2) that detoxify and eliminate carcinogens
Induce antioxidant enzymes
Prevent initiation: Prevent carcinogens from entering cells or binding to DNA
Prevent promotion: Regulate enzymes controlling cell division and that repair damaged cells
Indoles
Indole-3-carbinol
Diindolyl methane
Indole acetonitrile
Indole-3-carbinol: has the isocyanate bridge. Needs myroname to release the SCN (thiocyanate) to become indole -3-carbinole:
Epidemiology suggests indoles or metabolites play a role in cancer prevention (especially breast cancer)
Mechanism(s)?
Modulate estrogen metabolism & decrease carcinogenic estrogens (Inhibit estradiol activity)
Modulate cytochrome P-45O activities (Phase I),
Induce glutathione-S-transferase (Phase II)
inhibit cell proliferation in vitro
glucobrassicin-myrosinase-> indole-3-carbinol + thiocyanate
Bioavailability
Myrosinase is inactivated with heating
decreased bioavailability of isothiocyanates
Raw broccoli is best source of isothiocyanates
Cooked broccoli still has other benefits (carotenoids & vitamin C)
Dithiolthiones
Ability to protect against carcinogens in animals
Protective against breast, skin, lung, colon & trachea cancers
Induce glutathione synthesis and several Phase II enzymes
Allyl Sulfides
Allium Family: Garlic, Onions, Leeks, Chives, Scallions
Anti-CVD and anticarcinogenic activities
Decrease LDL, cholesterol and triglyceride levels – controversial (weak evidence)
Antithrombotic effects
Antioxidant activities (inhibit lipid peroxidation)
Stimulate GSH-transferase activity
May stimulate DNA repair
Allicin
Allyl Sulfides cont.
sulfoxide/thiosulfinate aroma component from garlic
released from alliin by alliinase activity
often assumed to be bioactive component
but unstable
preparations without (eg. aged garlic extract) still show bioactivities (antiplatelet, chemopreventive, hypolipidemic)
other active compounds (eg. S-allyl cysteine/mercaptocysteins, selenium)
Recommendations:
- BODY FATNESS
Be as lean as possible within the normal range of body weight - PHYSICAL ACTIVITY
Be physically active as part of everyday life - FOODS AND DRINKS THAT PROMOTE WEIGHT GAIN
Limit consumption of energy-dense foods
Avoid sugary drinks - PLANT FOODS
Eat mostly foods of plant origin - ANIMAL FOODS
Limit intake of red meat and avoid processed meat - ALCOHOLIC DRINKS
Limit alcoholic drinks - PRESERVATION, PROCESSING, PREPARATION
Limit consumption of salt
Avoid mouldy cereals (grains) or pulses (legumes) - DIETARY SUPPLEMENTS
Aim to meet nutritional needs through diet alone
BREASTFEEDING (Special Recommendation)
Mothers to breastfeed; children to be breastfed
CANCER SURVIVORS (Special Recommendation)
Follow the recommendations for cancer prevention
Conclusions and Recommendations
Phytochemicals have significant potential for reducing risks of chronic diseases
Diet should emphasize fruits, vegetables, whole grains
Eating a variety of foods ensures consuming a variety of phytochemicals
Functional foods?
Nutraceuticals?
Cruciferous Vegetables (Cruciferae Brassica)
kale kohlrabi mustard horseradish wasabi beet greens radishes
broccoli Brussel sprouts cabbage cauliflower collards arugula bok choy
Glucosinolates
more than 100 compounds
major sources
glucobrassicin
neoglucobrassicin
sinigrin
glucoraphanin
cabbage
broccoli
Brussel sprouts*
*best source
