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 science• Activity of genes = molecular biology• Individual = genetics/genomics• Health = physiology

A systems biology science : Multi – disciplinary

Nutrient is independent variable

Nutrient Gene Expression

Gene expression is independent variable

Nutrigenetics Definition Effects of individual genetic variation in

response to nutrient

Most common form of variation

Any two individuals share 99% of their DNA sequence

1. Single nucleotide polymorphism (SNP) 2. Changes in single base pair 3. Occur ~ 1 in every 1000bp of human genome

SNPs may alter regulation of gene expression, mRNA processing (splicing, half-life etc) and protein activities

Roles of Iron in the Cell

Transferrin Receptors (TfR)

Fe(III)2-Tf Tf

Proteins: Catalysis Electron, oxygen transport Structural stabilization Sensor of Fe, ROS Formation of protein-bound radicals

Storage and Sequestration: FerritinFerritin

Toxicity: Oxidative stress

[Fe]

[Fe]

[Fe]

An Overview of Iron MetabolismG

utB

lood

Cel

ls

• Low pH of stomach solubilizes Fe-containing ionic compounds.• Fe transporters facilitate absorption into blood stream

• Fe3+ ions are bound and chelated by Transferrin (Tf).• Transferrin transports Fe to tissues

•Maintains solubility•Keeps Fe ions unreactive

• Transferrin endocytosis is receptor-mediated (TfR)• Endocytosis results in Fe3+ release• Fe is distributed to topologically distinct regions of the cell via Fe transporter and/or channels (?)

• Usage: Protein components (Heme)• Storage: Ferritin (Fe2+)• Toxicity

Sources

• Heme iron

- animal ( ± 30%)

• Non Heme iron

- vegetable, legumes etc.

Absorptioniron status regulated through absorption

Increase- Acid in stomach- Heme iron- High body demand- Low body stores of iron- Meat protein factors

(MPF)- Vit C (converts ferri to

ferro)

Decrease- Phytic acid (dietary fibre)- Oxalic acid- Polyphenols (tea, coffee)- Full body stores of iron- Excess of other minerals

(Zn, Mn,Ca)- Reduction in stomach acid- Antacid

Iron in the intestinal lumen

Enterocytes in the crypts

Transport

- Transferrin is a protein that transports iron in the blood

- When iron stores are adequate all iron binding sites are saturated

-Transferrin can be used as an indicator of overload or deficiency

- Almost all cells in the body have transferrin receptor (TfR)

- Serum soluble Tfr (sTfR) is a good indicator of deficiency.

Internalisasi besi

Tahap deplesi besi dan indikatornya

Allen et al. 2000

Suplementasi besi gagal karena tingginya prevalensi kurang gizi kronik dan defisiensi berbagai zat gizimikro lain

Broek dan Lestky 2000

Among anemic pregnant women only 53% showed biochemical evidence of iron deficiency.

That is the maximum proportion of people among whom anemia could be expected to respond to the administration of iron

vitamin yang berperan dalam kejadian anemia

Vitamin B12• Defisiensi vitamin B12 dapat menyebabkan folat

tertahan dalam bentuk 5-methyltetrahydrofolate karena aktivitas dari enzim methyonine sintase tergantung vitamin B12

• terjadi defisiensi folat fungsional yang berkembang menjadi pengurangan folat vitamers yang dibutuhkan untuk sintesis dTMP dan terjadi reduksi availibilitas kelompok denovo methyl yang dibutuhkan untuk methylasi CpG, dan mengganggu ekspresi DNA

• Effek klinis awal dari gangguan defisiensi vitamin B akan menyebabkan anemia megaloblastik.

Vit B12 lanjutan

• Vitamin B12 juga dibutuhkan untuk methylmalonyl coA-mutase, dan defisiensi dari locus ini akan menyebabkan kegagalan methylasi arginin residu protein dasar dari myelin dan menyebabkan degenerasi yang ireversibel dari system saraf.

• Anemi pernisiosa merupakan masalah yang serius dan tanda awal anemia megaloblastik dapat ditutupi dengan intake folat yang tinggi, hal ini yang mendasari kebijakan untuk fortifikasi folate.

• Defisiensi vitamin B12 dan asam folat yang terjadi bersama-sama akan berakibat pada integritas DNA

Kelompok risiko tinggi anemia

• Ibu Hamil

• Ibu menyusui

• Bayi

• Balita

• Remaja ( t.u: putri)

• lansia

Ibu hamil

• Kebutuhan energi meningkat:– Suplai energi untuk peningkatan metabolisme– Pembentukan jaringan ( bersama dengan

protein )– Tambahan kurang lebih : 300 kalori/ hari

dibanding wanita yg tidak hamil ( 2200-2500 kal)

Kebutuhan ibu hamil lanjutan……..

• Kebutuhan protein :– Sumber utama pertumbuhan jaringan janin– Pertumbuhan bayi cepat– Perkembangan placenta– Pertumbuhan jaringan mamma dan uterus– Meningkatnya volume darah– Cairan amnion– Cadangan : selama hamil dan saat

melahirkan

Sumber makanan

• Protein komplit yang memiliki nilai biologis tinggi : susu, telur, keju, daging.– Sumber : vitamin A, B, besi, calsium

• Protein inkomplit dari tanaman : sebagai tambahan:– Sumber vitamin C, serat, PUFA, vitamin E,

antioksidan, asam folat