21 Glucosinolates Flashcards
What are glucpsinolates?
Phytochemicals (naturally occurring compounds in plants
- sulfer containing
- Brassica family of plants
- chemically stable
- biologically inactive
Food sources of glucosinolates?
Cruciferous veggies Brassica family - broccoli - cabbage - brussel sprouts - cauliflower - Kale
It is important to advance knowledge of phytochemical in relation to ….?
disease risk
Development of a food composition database for the estimation of ….
Dietary Intakes
Key structural features of glucosinolates
** recognize this structure
Thioglycosidic link (glucose - sulfer - R)
Sulfate Group
- R —- SO3- — O
- usually potassium (cation)
R group of glucosinolate structure is derived from?
amino acids
- highly variable
- approx. 100 identified
Enzyme type that breaks down glucosinolates
Myosinases
Where are myosinases located?
Within the same plant as glucosinolates, but seperate
What causes myrosinases and glucosinolates to come into contact
tissue damage (caused by pests)
harvesting
food processing
chewing
First step of glucosinolate metabolism, cleavage of thioglycosidic bond yields ..
Algycone
- removes glucose
After thioglycosidic bond has been cleaved from glucosinolate, how does metabolism proceed?
becomes unstable degrades spontaneously non-enzymatic rearrangment - sulfate released - several possible breakdown products - depends on side chain and presence of protein cofactors that modify enzyme action
R —- N ==== C ==== S isothiocyanate
Possible effects of glucosinolate breakdown products
- possible toxicological effects
- plant defence system (insects, fungi, etc)
- bitter taste in condements
- characteristic flower of numerous veggies
- ** potential anti-carcinogenic effect in humans
Most researched glucosinolate breakdown products? Why?
Isothiocyanates
- possible anti-cancer effects
3 specific naturally occurring isocyanates
PEITC
BITC
Sulforaphane
(broccoli) ?
Glucosinolate bioavailability is largely affected by?
food preparation methods
- myrosinase inactivated by cooked (no breakdown products)
What in the body can produce myrosinases?
Colonic Bacteria
Can you obtain Glucosinolate breakdown products after cooking brassica veggies?
yes
- colonic bacteria can produce myrosinases
Fresh vs Steamed broccoli study
- difference in urine/blood concentrations of isothiocyanate?
Fresh 3x higher isocyanate concentration than steamed
- some still in steamed
- hydrolysis of Glucosinolate likely by intestinal microflora
Isothiocyanate effect on carcinogen metabolism
chemoprotection
- increases body’s enzyme defence system against carcinogens
- modulate “balance” between phase I and II enzymes
- in liver and epithilial cells, including colon
What are phase I and II enzymes?
Metabolize xenobiotics
biotransformation enzymes
- deal with foreign compounds
- by making them water soluble
First line of defence against carcinogens
Phase I and II enzymes
better to have extra Phase I or phase II enzymes? why?
Phase II
- phase I makes carcinogenic intermediates worse, but easier for phase II to deal with
Phase I enzymes method
known as “activation enzymes” (ex. Cytochrome P-450 family)
- oxidation, reduction and hydrolysis reactions
- metabolize lipophilic pro-carcinogens
- make them “water soluble”
- allows phase II to act on them
Phase II enzymes method
“detoxification enzymes” (ex. GST glutathoine transferase family)
- metabolize phase I generated epoxides
- form inactive water soluble conjugates
- readily excreted in urine
also metabolize free radicals to inactive metabolites
Can diet modulate Phase I and II enzymes?
Glucosinolate breakdown products “increase” phase II enzymes (glutathione transferases)
- no effect on phase I
- want more II than I
5 mechanisms glucosinolate breakdown products protect against cancer
- modulation phase I and II enzymes
- increase phase II - indirect anti-oxidant effects
- phase II metabolize free radicals - Induces apoptosis
- independent of enzymes - Blocks cell cycle
- Modifier of “Estrogen” Metabolism
Isothiocyanates and Cancer (studies)
Animal Studies
- inhibition of carcinogenesis
Cell culture studies
- inhibition of cancer cell growth (blocks cell cycle)
- increase apoptosis
What specific metabolite effects estrogen metabolism?
Indole-3-carbinol
Indole-3-carbonal on estrogen
increase anti-estrogen metabolites
decrease pro-estrogen metabolites
- in urine
- increased ratio of 2/16 hydroxylated estrogen metabolite
2/16 hydroxylated
used as a biomarker in studies evaluating the cancer-protective effects of an intervention
- higher = lower risk cancer
- indole-3-carbonal increases this to estrogen metabolite ratio
What can complicate the relationship between glucosinolate and cancer risk?
Genetic polymorphisms
- affects expression of transcription factors
- ligand binding affinity of receptors
- alter chemopreventative effects
Genetic Polymorphisms
individual differences in cancer risk in response to cruciferous veggies exposure
- secondary to genetic and associated functional variations in biotransformation enzymes
Studied: GST (phase II)
Interaction
influence of phytochemical on a defined polymorphism
Broccosprouts
20x the sulforaphane-glucosinolate (SG) than broccoli
- tested 50 different kinds of broccoli seeds
- found one that yielded sprouts with highest and most consistent glucosinolate levels
