Clinic Nutrition (vitamin 2009)

Regulation of gene expression and cellular differentiation
• RA are transported into nucleus by binding with cytoplasmic retinoic acidbinding proteins (CRABP) then nuclear retinoic acid receptor proteins. • Specifically, all-trans-RA binds to retinoic acid receptors (RAR) and 9-cisRA binds to retinoid X receptors (RXR). • RAR and RXR form RAR/RXR heterodimers • The heterodimers bind to retinoic acid response elements (RARE) of the chromosome to allow the complex to regulate the rate of gene transcription, thereby influence the synthesis of certain proteins. • RXR may also form heterodimers with thyroid hormone receptors (THR) or vitamin D receptors (VDR). In this way, vitamin A, thyroid hormone, and vitamin D may interact to influence gene transcription.
Vitamin A: physiological function
Immunity: anti-infective vitamin
• The skin and mucosal cells (cells that line the airways, digestive tract, and urinary tract) function as a barrier and form the body's first line of defense against infection • Retinol and its metabolites maintain the integrity and function of these cells. • Vitamin A and retinoic acid (RA) play a central role in the development and differentiation of WBC, such as lymphocytes, which play critical roles in the immune response • Activation of T-lymphocytes, the major regulatory cells of the immune system, appears to require all-trans-RA binding of RAR • Prevent cancer: beta-carotene against ROS
retinal and its esters have a yellowish-green fluorescence
Vitamin A metabolism
Vitamin A is obtained from the diet and transported in the blood as a complex with retinol-binding protein (RBP) and transthyretin (TTR). In the liver, retinol is esterified to retinyl esters and stored in stellate cells. In other tissues, including gutassociated immune cells, retinol is oxidized to retinal by alcohol dehydrogenases (ADHs) or short chain dehydrogenase/reductases (SDRs). Retinal is then oxidized to all-transretinoic acid in an irreversible reaction that is catalysed by retinal dehydrogenases (RALDHs). Retinoic acid acts on immune cells by binding to the retinoic acid receptor (RAR). Retinoic acid is catabolized in the liver and in other tissues by the enzyme CYP26 and its metabolites are eliminated in the bile and urine.
Deficiency of Vitamins
Deficient intakes
(1) Cause:
Problem of absorption
Increas: Critical deficiency: Disease
Marginal deficiency:
• Solubility:
• Water-soluble (Vit. Bs,C): Easy excretion from urine: sensitive to insufficient intake but rare intoxication • Fat-soluble (Vit. A, D, E, K): High retention in body: toxic after excessive intake
Effects of vitamin A metabolites on gut mucosal immunity
Vitamin effects on the immune system: vitamins A and D take centre stage. Nature Reviews Immunology 2008 (8): 685 - 698
2
• Classification:
5 1
CH3 CH3
10
12
14
• Preformed vitamin A: animal food
• Retinol, retinal, retinoic acid (usually present as ester, primarily retinyl palmitate)
Influence health without symptoms
Vitamin A
Fat-soluble vitamin important for vision and immune
Vitamin A: Preface
• Vtiamin A: a family of bi-polar molecules with retinyl group (a beta-ionone ring attached isoprenoid chain) CH3 CH3 CH3 and retinol-like bioactivity CH OH
• George Wald was awarded the Nobel Prize for medicine in 1967 for his discovery of the role of VitA in the visual system.
Vitamin A: physiological function
• Provitamin A: carotenoids in plant food
• Alpha-, beta, gamma-carotene • Beta-cryptoxanthin（隐黄素）
CH3 CH3 CH 3 CH3 CH3 15 15' CH3 CH3
CH3 CH3
CH3
• Most of carotenoids (90%) cannot convert into vitamin A
Vitamin A: Lung Cancer
• About 9,000 people (smokers and people with asbestos exposure) were
assigned a daily regimen of 30 mg beta-carotene, while a similar number
deficiency disease.
Vitamins: Preface
Classification
• Discovery history: A, Bs, C, D, E, K……
• Function: ascorbic acid
• Chemical construction (popular name): retinol, riboflavin, thiamine,……
of people were assigned a placebo. • After four years of follow-up, the incidence of lung cancer was 28% higher in the supplemented group compared to the placebo group. • Possible explanation: oxidative environment of the lung, created by smoke or asbestos exposure, gives rise to unusual carotenoid cleavage products, which are involved in carcinogenesis.