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Gizi 8 Maret 2009 FInal
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Transcript of Gizi 8 Maret 2009 FInal
Ignatius Hapsoro Wirandoko
Dipresentasikan pada Seminar Nasional “Healthy Diet for Healthy Life,How to Eat Healthy Diet that Your Body and Soul Agree”
Program Studi Ilmu Gizi Fak Kedokteran Univ. DiponegoroSemarang, 08 Maret 2009
Nutrigenomics:Molecular nutrition of genetic
variation linked to diet
Nutrigenomics Definition
Analyzing the effects of diet on the activity of on individual’s genes and health and the effect of an individuals genes on metabolism of dietary chemicals
Diet = nutritional scienceActivity of genes = molecular biologyIndividual = genetics/genomicsHealth = physiology
A systems biology science : Multi - disciplinary
Nutrient is independent variable
Gene expression is independent variable
Gene Expression
Nutrient
Effects of individual genetic variation in response to nutrient
Nutrigenetics Definition
Any two individuals share 99% of their DNA sequence
Most common form of variation Single nucleotide polymorphism (SNP) Changes in single base pair Occur ~ 1 in every 1000bp of human genome
(~ 3 million in human genome)
SNPs may alter regulation of gene expression, mRNA processing (splicing, half-life etc) and protein activities
Ancestral diet
Modern diet
Molekul mechanisms of genetic variation Linked
diet
Selection pressures leading to metabolic programming, i.e., SNPs tailor man to enviroment
Human diseases resulting from incompatibility between genetic/metabolic programming and modren diet
Dietary Nutrients
Micronutrients Macronutrients
Other food components
Transduction of signal via sensory mechanisms
Metabolism
NUTRIGENOMIC ASPECTS OF CELLULAR FUNCTION
NUTRIGENOMICS
Genomics Transcriptomics Proteomics Metabolomics
Genomics, transcriptomics, proteomics, metabolomics as analytical tools in molecular nutrition
DNA mRNA MetabolitesProtein
Sequencing and Genotyping
Pattens ofGene expression
Synthesis and Structure of Proteins
Profile and FuctionOf metabolites
Examples of Nutrient Interatcions with Genotype That Have Implications for Human Health
Gene SNP/Isoform NutrientMTHFRAPOEAPOA 1GPX4HFE
C677TE2+ , E3+ , E4-75 (G/A)3‘ – UTRC282Y, H63D, S65C
Folate, alcohol- 3 PUFAPUFASeleniumIron
Genetic variation (SNP) may contribute to disease differentials
Several alterations will be “diet responsive” and can be rendered harmless
Challenge Defining the right diet for the right population Tailoring dietary recommendation based on genetic when
appropriate
Nutrigenetics
SusceptibilitySNP1SNP2
PoorNutritionIn utero
FoodComponent I
Time
Smoking
ProtectiveSNP1
GoodNutritionIn utero
FoodComponent 2
Physicalactivity
Healthpendulum
Health Disease
THE HEALTH PENDULUM
Fatty acid
sC
ho
lesterolP
rotein
&
amin
o acid
Carb
oh
yd
rates
i.e
., glu
cos
eV
itamin
AB
ioflavo
no
ids
Vitam
in E
Xen
ob
iotics
Zin
cIro
nC
alcium
Vitam
in D
•Sterol regulatory element biding protein•Hepatocyte nuclear factor•Carbohydrate response element biding protein•Peroxisome proliferator activated receptor•Liver X receptor
•Modifies gene expression via signal transduction pathways•Pregnane X receptor
•Liver X receptor•Farnesoid X receptor•Pregnane X receptor
•Calcineurin/nuclear factor of activated T cells
•CCAAT/enhancer-biding protein
•Iron regulatory protein 1 and 2
•Sterol regulatory element binding protein•Upstream stimulatory factor•Carbohydrate response element binding protein
•Metal responsive transcription factor
•RAR•RXR
•Constituvenly active receptor•Pregnane X receptor
•Estrogen receptors•Nuclear factor xB
•VDR
Trancription factor Nutrient ligand
Tran
sciptio
n facto
rs and
their
Co
mp
on
ent S
NP
s con
tribu
te to
Th
e mo
saic of n
utrig
eno
mic effects
Th
at mo
dify p
hen
otyp
e, and
C
on
tribu
te to h
um
an in
divid
uality
GENETIC BUFFERING UNDERPINS NUTRIGENOMIC RELATIONSHIPS
PHENOTYPIC STABILITY
A more robust cellular integrity
A lessrobust cellular integrity
PHENOTYPIC INSTABILITY
•Health•Reproductive efficiency•Enhanced competitiveness
•Desease•Reproductive inefficiency•Reduced competitiveness
Natural selection acts to promote a robust phenotype in the face of nutrient variability. Genetic buffering confers stability and is achieved via interactions between gene loci, nutrient and genes, biologically active nutrients and the metabolome, and nutrients with nutrients. Other buffering mechanisms include gene duplication, a complex regulatory mesh of epistatic gene interactions, and protein-protein interactions that lead to molecular stability
Stochastric variables in the external enviroment:i.e.,avaviability of food nutrient, and influence of mutagenic processes, are subject to genetic buffering as a mechanism to impprove phenotypic stability
The Balances between phenotypic outcomes with respect to nutrition and genetic buffering
Important micronutrient–gene interactions, with particular reference to the effect ofcertain vitamins and minerals on the genomic machinery and/or gene product.
Some Important Micronutrient–Gene Interactions
Dietary Component
BackgroundInformation
Effect on Genomic Machineryand/or Gene Product
Retinoic acid(vitamin A)
RXR forms homodimers andheterodimers with vitamin D,PPAR, thyroid hormone, andCOUP receptors
Binds either RXR or RAR nuclear retionoid receptor and enhances transcription, although in absence ofretinoic acid, heterodimers repress gene expression
Ascorbic acid(vitamin C)
Oxidative DNA damage in vitaminC depletion (formation of 8-hydroxyguanine)
Enhances transcription of procollagen and translation of lysyloxidase
PyridoxalPhosphate(vitamin B6)
Modulates responsiveness ofsteroid hormone receptor
Attenuates transcription
Riboflavin(vitamin B2)
Flavin cofactor for 5,10MTHFR May interact with cellular folate to influence elaboration of DNA (1-C unit from folate donated to thymine)
Folic acid Provides 1-C unit for purine, pyrimidine, and methyl groups May modulate both expression of DNA via CpG methylation pattern and elaboration of DNA via provision of thymine. If 1-C shortage, uracil ismisincorporated and DNA becomes unstable
Vitamin D Vitamin D receptor forms a heterodimer with RXR Enhances transcription of calcium binding proteins
Vitamin K Growth arrest specific gene 6 product contains γ -carboxyglutamate residues
Regulates apoptosis, but it does not interact directly with genomic machinery
α-Tocopherol(vitamin E)
Antioxidant properties. Ameliorates damage to DNA from excess iron. Induces two signaltransduction pathways that act at several genes, but also acts independent of these two pathways
Protects genomic machinery from freeradical damage. Alters activity of protein kinase C and phospotidylinositol 3-kinase. This in turn regulates the expression of several genes . Also actson genes independent of these kinases
Calcium Critical for intracellular signaling Increased transcription of c-fos, c-jun,c-myc
Iron During deficiency, iron-regulatory protein binds mRNA and promotes synthesis of transferring receptor protein while ferritinproduction is repressed. The net effect is to increase iron utilization
Enhances transcription of metallothionein and translation of ferritin
Magnesium Required for nucleic acid polymerase enzyme activity Maintains fidelity of the DNA blueprint
Potassium Influences transcription of aldosterone synthase
Selenium Selenocysteine residue in glutathione peroxidase provides antioxidant properties
Helps prevent free radical damage to genome
Zinc Structural motif of zinc finger transcription factors Augments transcription factor binding
TRANSCIPTOMICS
APPLICATIONS TECHNIQUES
Screening and development of new antioxidants
Assessing potential effects of antioxidants
Defining biomarkers of oxidative stress
Evaluating the bioavailability of antioxidants
Studying redox sensitive signal transduction pathways
Differential display
cDNA arrays and Gene chips
Serial Analysis of Gene Expression
RT-PCR
Northern blotting
Analytical techniques and potential applications of transcriptomics in the fileds of free-radical research
• DNA micro arrays
• Protein chipsLarge scale genomics and proteomic investigations monitoring of the expression of thousands of
genes in response to diets
how nutrients modify;- cancer risk- chronic disease- aging
most human disease are largely avoidable by lifesyle changes
Nutrigenomics at the - forefront of preventive medicine- special emphasis on the gene regulatory activity of
- antioxidants- phytochemicals- micronutrients
Leading edge Laboratory Tools;
2 mol glutathione (GSH)
NADP+
Glutathione reductase
NADPH
Radical generatedLipid peroxides
1 mol reduced glutathione (GSSG)
Glutathione peroxidase enzyme protein with a selenocysteine residu at the catalytic site
+H3N ─ CH
CH2 ─ │
│C = 0│0
SeH
Free radikal
Mechanism of selenium as on evolutionary pressure on gametogenesis
5, 10-Methylenetetrahydrofolate
5-Methylenetetrahydrofolate
Equlibrium in favor of 677C allele
Equlibrium in favor of 677T allele
C667T-MTHFR one carbon flux B2
S-Adenosylhomocysteine Homocysteine
S-Adenosylmethionine
methionine
Genomic methyiations
B12
Methyionine synthase
Methyionine biosynthesisPertubations may increase homocysteineAnd hence vascular disease. They may alsoInfluence DNA methylationPatterns and gene expressionHomocysteine is alsoConsidernet to be embryotoxic
dUMPThymidylate synhase
dTMPNucleotide biosynthesis and the elaboration of DNA
Pertubations may influence embryogenesis; inadequate folate due to a poor diet and 677-MTHFR might lead to uracil misincorparation in DNA, genomic instability, and loss of the developing embryo. It may also promote cancer
Contemporary selection pressure from periconceptional folate supplements
Schematic of vitamin A and gene regulation
Micronutrients that act directly or indirectly as antioxidants or influence DNA expression
Vitamin A
Vitamin E
Folicacid
Vitamin D
Zn,Se,FeMg, Cu
Vitamin B2
Vitamin B3
Vitamin B6
Vitamin C
Vitamin B12
Nuclear DNA Damage
Threat and management of deleterious radicals generated by cellular respiration
Freeradicals
+O2
Mitochhondrial DNA Damage
Superoxidedismutase
Catalase
H2O2
H2O and
O2
Superoxide radical
ATP energy
O2 +
Glu
co
se
Membrane Damage
Antioxidants evolutions & Human Health
Homocyteine : genetic and nutritional factors
MTHFR - Homocyteine
Oxidative stress Reduce NO
Reduce tetrahydro biopterin
Low methylation
Homosisience
Metionin(Borto & Yang,2000)
MTHFR:C677C (normal)
C677T (akt rendah)
Metioninsintase
5 metilTHF
5,10 metilen THF
various mechanisms involved in the deleterious actions of homocysteineupon cellular processes.
Homocystein and modern society
Cellular genomic and nongenomic effects of isoflavones. The effects differ according to thetype of tissue and the number of estrogen receptors within that tissue. The effect on reproductive tissueis of particular interest and may influence reproductive efficiency.
Causes of Metabolic Syndrome
Various Factors Cause Metabolic Stress
Food
Stress
Pollution
Second hand smoke Genetic
Inheritance
…Lack of Exercise
Oxidative Activities
Cholesterol
Toxine
Diabetes
BacteriaGerm
Lack of enzyme
Gene Enviroment
INSULIN RESISTANCE
Effect of cytokines TNF,
IL 1 and IL6
Raised blood lipids
Production ofOxidant molecules
Acute phaseprotein
Fever Glucose Synthesis
AppetiteLoss andlethargy
Plasma copper
Plasma ZnPlasma Iron
Increased urinaryNitrogen sulphur
And mineral losses
Loss of leanTissue andfat
Fat proliferates abnormally (OBESITY)
chytokines
chytokines
Chronic inflammation develops
How Does Abdominal Obesity CauseInsulin Resistance
A collection of metabolic risk factors that accelerate the onset of diabetes, heart disease, stroke and certain cancers.
Metabolic SyndromeHealth Destroyer
Proinflammatory Cytokines Released
Glucose Uptake Decreases
Blood Glucose Levels Increase
Hyperglycermia
Hyperinsulinemia
Pancreas Increases Insulin Production
Triglycerides Released to Blood Stream
Cardiovascular Disease
Adipose tissue expands
O2 = dangeraous friend (a free radical)
evolutionas the terminal electron acceptor for respiration biradical ;
~
Others : - SUPEROXIDE ANION/ HYDROL RADICALS- oxidative- metabolism, and energy production- ionizing radiations
endowed with a higher chemical reactivityinvolued in - regulation of signal transduction
- gene expression, - activation of receptors,
- nuclear trancription factors,- oxidative damage to cell components
- antimicrobial and cytotoxic action of immune system cells neutrophils and macrophges in
aging &age related degenerative diseases
OXIDATIVE STRESS
Oxidative stress can lead to cell and tissue injury
Free radical generated by Nitric oxide synthase (NOS)
modulates physiological responses in the circulation
e.g.- vasodilatation (eNOS)
- signaling in the brain (nNOS) During inflamation : 1/3 isoenzyme is induced (iNOS)
everproduction of NO tissue damage
- + superoxida anion a strong oxidant : peroxynitrite Oxidation of
- lipid
- protein
- DNA by peroxynitrite tissue injury
NITRIC OXIDE (NO)
ROSNOS
redox regulation of cell functions
Oxidative stress as a major upstream component in
- the signaling cascade (in inflamation responses)
- stimulation of adhesion molecule, and
- chemo attractant production
H2O2 decomposes in the presence of transition metals to the highly reactive hydroxyl radical by 2 major reactive
- hydrogen abstraction and addition Oxidative damage to:
- lifoid- sugar- nucleic acid
H2O2 : an important signaling molecul
activate NFKB (transcription factor in inflammatory responses)
Low concentration :
- regulated cell signalling
- stimulates cellprofiferation
High concentration :
triggers apoptosis necrosis
Free radicals
Secondary ; most cases Causal
A Delicate balance : oxidands – antioxidants
proper balance healthy aging
Oxidative stress
1)Redox status the degree to which a cells components in the oxidized state
the reducing environment inside cells helps to prevent oxidative damage
maintained by (remove ROS)- oxidative metabolism- the action of antioxidant enzymes,
- superoxide dismutase- catalase- selenium dependent glutathione
reductase- glutathione hydroperoxidase- thioredoxin hydroperoxidase
- substances glutathione thioredoxin, vitamin E, C.
2) Depletion of antioxidants
Index of oxidative stress
- Thiol redox status- GSSG/ GSH ratio (Glutathione disulfide/ glutathione)- redox couples ratio
- NADPH/NADP- NADH/ NAD- Thioredoxin reduced/ thioredoxin oxidized- Dihydrolipoic acid/ lipoic acid- lactate/ pyruvate
Energy status of the cell(ratio ATP/ ADP + AMP)
Current hypotheses: How oxidants – antioxidants modulate ? lowering oxidative stress cell and tissue fuction can have a health benefit.Can be - over produced free radicals
- natural antioxidant system defenses weakened oxidative injury - heart disease
- cancer - neurodegenerative
disordersOxidation of human LDL : early step in the progression and
eventual development of atherosclerosisOxidative DNA damage
initiate carcinogenesisEnvironmental source of ROS oxidative stress disease
- UV radiation- Ozon- Cigarette smoke- others
FROM EPIDEMIOLOGICAL STUDIES : antioxidant status (vit C, E)
~ risk of several disease- Cataract- Cancer- Neurodegenerative disorder- Rheumatoid arthritis- DM
scientific evidenceClinical - prevention
- treatment
As - a primary cause - a secondary complication in many disorders
- inflamatory bowel disease- retinal ischemic- CVD and restenosis- AIDS- adult respiratory distress syndrome- stroke- Parkinson’s disease- Al zheimers disease
Major natural
antioxidant enzyme/ substances (in foods & beverage)
- vit E, A, C- flavonoids- polyphenols- caretenoids- lipoic acid- coenzyme Q10- carnitine- other micro nutrients
Trauma/infection/burn
Immune system activation
Pro-inflammatory cytokines
oxidants Antioxidantdefence
Tissuedamage
Pathogenkilling
FeedbackSystemsIL10, HeatShock proteins
Creation of a hostile enviroment
NutrientRelease fromHost tissues
Sulphuraminoacids
Antioxidantdefencesstrenghened
GlutathioneSynthesis
Appetite loss
T and B Cells
Glucose
Glutamine
Immunonutrition
Oxidants
Vit EReduced
Vit Eoxidised
Dehydroascorbicacid
Ascorbicacid
Methionine
Homocysteine
Cysteine
GlutathioneGSSG
GlutathioneGSH
Vit B6
Riboflavin
Glutathionereductase
Inflammatory stimuli LPS, Oxidants, stress
AP1 NFKB
CellProliferation
IL2
AcutePhaseprotein
IL1,IL6,IL8,TNF
GSHsynthesis
Adhesionmolecules
HIVreplication
Transciptionfactors
Antioxidants
Antiageing, Antiatherogenic, Anticarcinogenic,Immunomodulatory, Neuroprotective Effects
Preventions of OxidativeDamage towards Lipids
Proteins and DNA
Redox SignallingMolecules
Free Radical ScavengersMetal Chelators
Antioxidants as free-radical scavengers, metal chelators, and redox signaling molecules – both prevention of oxidative damage towards lipids, protein, and DNA as well as redox signaling contributes to their beneficial effects.
InhibitoryEffect of
Vitamin E onNitric oxide and
Cytokine production
Scavenger receptorexpression
Smooth muscleCell proliferation
LDL oxidation
Platelet adhesionAnd-aggregation
Cell adhesion protein expression
Molecular mechanisme for the anti-atherogenic activity of VE
Receptors
PhosphataseKinases
Gene Expression
Protein levels
Enzyme Activity
Oxidants Antioxidants
Transcription Factors
Cell receptors, cellular key enzymes, and transcription factors as molecular targets of oxidants and antioxidants
Rekayasa genetika pangan
KEBODOHAN (logos)
KESERAKAHAN (eros)
Kanker (Musibah) GLOBALISASI
KEARIFAN LOKAL
Pangan - GIZI (anugerah)
BIOTEKNOLOGI
NUTRIGENOMIC
Perilaku
GAYA HIDUP
KANKER LINGK- Kontaminan- Pestisida- Limbah
• Pola/kebiasaan makan
• Rokok, alkohol• Sedentary (obeis)
- Genotoksik/ pro kanker- Anti kanker
- Olah- Simpan- BTP- Plastik
GLOBALISASI
Pangan
Fenotipe Sehat
Fenotipe Sakit
Ekspresi gen/ fenomena epigenetik
RISETEKOLOGI
RISETEPIDEMIK
Uji in Vitro
Uji Hewan
UJIKLINIS
Fakta Epidemiologis
Kashmir : Ca. Oesofagus ~ pengolahan teh + garam
Skandinavia : Cancer lambung & colon ~ daging merah
Migran Jepang : kacang cycad
Mesir : Cancer hati ~ bijian disimpan
Kaukasus : Cancer payudara ~ lemak
Ceko-Polandia : Lemak >< kubis
China : teh hijau, bumbu/ rempah cara masak singkat
PANGAN KARCINOGENIC Geno Toksik~ Alamiah : • hidrazin
• safrole• estragole• psoralen
Buatan/ perilaku manusia :prose
s• Simpan : Aflatoksin, Patulin, Citrinin • olah : panas tinggi (goreng, bakar)
aditif pangan
residu minyak goreng& Lemak trans (peroksida lipid) pengasapan langsung garam/ pengasinan
– PAH– HAA– NOC• etanol
• sacharin• karamel• furyl furamid• pewarna azo • nitrat (III, V)
Energi (+ OR minimal) Alkohol berlebih ROS endogen
Asupan :
KONTAMINAN Lingkungan Pangan(Via: mata rantai pangan)
Antropogenic environtment pollutant
Mutagenik - Karsinogenik Polutan organik PCB (PCDD, PCDF, VOX, Pestisida)
Polutan anorganik
• Nitrat (III, V)• Benzo [a] pyrene• Pestisida: Khususnya organochlorin: DDT,Chlordane,lindane,DDE,Aldrin• Plastik-styrofoam kemasan (vynil-chlorida)• Benzene• Dioxin• Organohalogen votatil air PDAM• Logam berat; Pb, Ni, As, Cr
Reparasi SEL
RegulasiHormonal
Respons Radang
Metabolisme Karsinogen
DiferensiasiKematian SelTerprogram
Siklus SEL
KOMPONEN BIOAKTIFPANGAN
Cegah terjadi Hambat perjalanan keganasan Halangi kekambuhan
Gambar : Modulasi Komponen pangan pd Sel Kanker
HANAHAN & WEINBERG
Mandiri signal tumbuh
Insensitif signal hambat tumbuh
Hindar apoptosis
Replikasi tak terbatas
Angiogenesis
Invasi - metastosis
2001 : proyek genom manusia tuntaspenggunaan dalamriset gizi :- genomik
- transkriptomik- proteomik- metabolomik
nutrigenomik
era post genomik
Biomarker
Lokasi sel target
Tahapan Spesifik
Efek spesifik
Dapat dipantau adanya perubahan
risiko terhadap respon intervensi gizi
Dapat dipantau adanya perubahan
risiko terhadap respon intervensi gizi
MEKANISME MOLEKULER DIET ANTI KANKER
Aktivasi antioksidan• pembersihan radikal bebas• reduksi stres-oksidatif• pengurangan “nitrasi,nitrisasi)• pencegahan ikatan DNA
Hambat proliferasi sel induksi diferensi sel hambat ekspresi onkogen, induksi ekspresi gen penekan tumor induksi “henti siklus sel” dan kematian sel terprogram Induksi enzim & peningkatan detoksifikasi: (enzim fase III, GPX, SOD) Hambat enzim (COX-2, iNOS, Xanthine oksidase, enzim fox I)
• anti pembentukan p. darah baru• hambat adhesi sel (lengket) & invasi• regulasi metabolism H. steroid & estrogen• aktivasi anibakteri-virus
VARIASI DIIT & FAKTOR GENETIK
Respon terhadap intervensi diit
Diit bersifat individual (Personalisasi diit) ~ variasi ekspresi gen :
protein transport reseptor enzim katabolis
Penanda biologisperubahan fenotipe :
proteomic metabolomic
Mis: aktivitas dehydrogenese alkohol Kaukasus > Jepang
Regulasi pembelahan sel
• genistein (isoflavon), fitoestrogen kedele
Signal Antitumbuh
• flavonoid buah sayur• n.3. FA : EPA, DHA ikan• resveratrol anggur• Vit A, Vit D Apoptosis
• resveratrol anggur merah• lyeopere teh• carotene sayur• allyl sulfur bawang putih• caffeic acid, ester propolis• curcumin temu lawak,madu,
Angiogenesis
• Retinoid sayur buah • EGCG teh hijau• Curcumin •Vit D
• Katekin teh hijau• EGCG teh hijau• Resveratrol• n-3Fa, EPA, DHA
Replikasi tak terbatas
Invasi metatase
• Katekin• EGCG the hijau + hitam
DIIT BERBASIS TARGET MOLEKULER
ANTI Oksidan
Et, Vitamin C Caroten Se EGCG Quercetin Genestein Taxifolin
ANTI Radang
n-3, EPA DHA minyak ikan Vit A, Vit E Bromelein Curcumin Resveratrol Quescetin EGCG
Detoksifikasi
Regulasi
Enzim xenobiotik : Glukosinolat brocoli
Epigenik : - Folat- Vit B, 12, B2, B6, methionin- Zn, Se- Retinoid acid
KHEMOPREVENSI KANKER Mikronutrient : Vit A, D, E, C, folat, Se Komponen bioaktif :
Makronutriet : omega 3, spingolipid, CLA
Serat
Carotenoid :• Carotene (..)• Lutein• Lycopene
Fenolic : • Fenolic acid• Flavonoids• Stilbene• Tannin• Coumarin
Organosulfur : • Isotiosionat• Indole• Alyl sulfur : sulfida
- Flavonols (Quercetin)
- Flavones (Apigenin)
- Flavanols (Catechin)
- Flavanone (Naringetin)
- Anthocyanidine (Cyanidin)
- Isoflavonoid (Genistein)
PREVENSI (Lain) Intensif penggunaan fitokimia
• buah• sayuran• biji utuh• serat• produk (ikan, kedele)• susu rendah lemak
kontrol BB, cegah obesitas Olah raga/ latihan minimal 30 menit kurangi makan (goreng, bakar/grill, asap, asin) kurangi lemak jenuh, tak jenuh trans) maks 25% Stop rokok, minum alkohol minimal
KHEMOPREVENSI DIIT & TARGET MOLEKULER
Mekanisme Target Molekuler Khemoprev. Diit
Hambat tangkapanKarsinogen
As. Empedu Kalsium
Hambat aktivasi karsiongen Sitokrom P450s -PE ITC-Indol -3- carbinol-Isoflavon
- PG Synthase Hydroperoksidase Slipoxygenase- As. empedu
Curcumin
-Urosdial
Dexoksifikasi karsinogen GSH/ GST NAC bisulfida
Cegah ikat karsinogen-DNA Sitokran P450s Katekin
Luas + tingkatan Reparasi DNA
ADP riboxyl transferete
NAC, Protease, Inhibition
Modulasi hormonAktivitas fc tumbuh
- Reseptor estroge- Steroid 5 reductose- IGF.1- AP-1- PPARs
-Isoflavon-Katekin-Isoflavon,,Likopen-Retinoid
MEKANISME DIET (lanjutan)
Hambat aktivitas onkogen FP transferase Limonen, DHEA
Hambat metabolisme poliamin ODC induksi Retinoids, curcumin, katekin
Induksi diferensiasi terminal TGF- Retinoids, vit D nofloam
Restorasi respons imun TNK limfosil sel langerhons
Selenium katekin
Reduksi inflamasi NF.KB EGCG, resveratrol, curcumin
Hambat prod ekosanoid Cycloxygenne & lipoxygenne
Curcumin resveratrol EPA, DHA, Katekin
Akeselerasi komunikasi inter sel
Connexin 43 Lycopene retinoids
Induksi Apoptosis - TGF - Rosfarelisasi- Arachidonic Acid- Caspase
-Retinoid isoflavon vit D-Penillyl alcohol limonen,
DHEA-Retinoic acid-Retinoids
Induksi senesens Telomerase Vit D retinoids
Hambat angiogenesis FGF receptorTyronin kinaseTranmodulin
Isoflavon restinoid
Koreksi imbalansi metilasi DNA
Cp6 island metilasi Asam folat
Hmbt defradesia membran basal
Collagenase IV Proteese inhibisi
Hambat sintesa DNA G.6.P dehydrogenase DHEA
MEMERANGI KANKERAICR Piramida Pedoman Makan
• keberagaman sumber pangan + proporsi harian• Pembatasan asupan
- Energi- Lemak- Gula sederhana
• Lemak
- buah-sayur- karbohidart komplek- serat
• tinggi asupan
- n-3- FA
Keseimbangan Energi Positif- gagal regulasi homeostatis (proliferasi, voskularisasi)- ritme metabolisme stress oksidatif/ internal- efek biogenetik E-radang-kanker
Tenets of Nutrigenomics
1.Improper diets are risk factors for disease2.Dietary chemicals alter gene expression and/or
genome structure3.Influence of diet on health depends upon an
individual’s genetic make up4.Genes regulated by diet play a role in chronic
diseases5.“Personalized nutrition” – diets based upon
genotype, nutritional requirements and status – prevents and mitigates chronic disease