Neuroergonomic

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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

Fe(III)2-Tf Tf

Transferrin
Receptors (TfR)

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

[Fe] Storage and Sequestration: Ferritin

[Fe] Toxicity: Oxidative stress


An Overview of Iron Metabolism

• Low pH of stomach solubilizes Fe-containing ionic


Gut

compounds.
• Fe transporters facilitate absorption into blood stream

• Fe3+ ions are bound and chelated by Transferrin (Tf).


Blood

• 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
Cells

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.
Absorption
iron status regulated through absorption

Increase Decrease
- Acid in stomach - Phytic acid (dietary fibre)
- Oxalic acid
- Heme iron
- Polyphenols (tea, coffee)
- High body demand - Full body stores of iron
- Low body stores of iron - Excess of other minerals
- Meat protein factors (Zn, Mn,Ca)
(MPF) - Reduction in stomach acid
- Antacid
- Vit C (converts ferri to
ferro)
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

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