Vitamin A

The Natural Thyroid Diet

The Natural Thyroid Diet

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Retinoic acid (RA) interacts with receptors in the nucleus. RA binds to steroid and thyroid hormone receptors, which are a family of ligand-sensitive transcription factors. All-trans RA binds to the RA receptor (RAR), whereas 9-cis RA binds to the retinoid-X receptor (RXR). The binding of the heterodimer RAR/RXR to a specific "retinoic acid response element (RARE)" on DNA regulates gene transcription (Figure 3.3).

Vitamin A is probably best known for its role in vision (Figure 2.10) however, most of the physiological effects of vitamin A are a consequence of its hormone-like role in cellular differentiation; the morphogenetic properties of RA may stem from the activation of developmentally regulated genes by RA receptor (RAR) complexes. Indeed, women who

Table 3.1. Important micronutrient-gene interactions, with particular reference to the effect of certain vitamins and minerals on the genomic machinery and/or gene product.

Some Important Micronutrient-Gene Interactions

Table 3.1. Important micronutrient-gene interactions, with particular reference to the effect of certain vitamins and minerals on the genomic machinery and/or gene product.

Some Important Micronutrient-Gene Interactions

Dietary

Background

Effect on Genomic Machinery

Component

Information

and/or Gene Product

Retinoic acid

RXR forms homodimers and

Binds either RXR or RAR nuclear

(vitamin A)

heterodimers with vitamin D,

retionoid receptor and enhances

PPAR, thyroid hormone, and

transcription, although in absence of

COUP receptors

retinoic acid, heterodimers repress

gene expression

Ascorbic acid

Oxidative DNA damage in vitamin

Enhances transcription of procollagen

(vitamin C)

C depletion (formation of 8-

and translation of lysyloxidase

hydroxyguanine)

Pyridoxal

Modulates responsiveness of

Attenuates transcription

Phosphate

steroid hormone receptor

(vitamin B6)

Riboflavin

Flavin cofactor for 5,10MTHFR

May interact with cellular folate to

(vitamin B2)

influence elaboration of DNA (1-C unit

from folate donated to thymine)

Folic acid

Provides 1-C unit for purine,

May modulate both expression of DNA

pyrimidine, and methyl groups

via CpG methylation pattern and

elaboration of DNA via provision of

thymine. If 1-C shortage, uracil is

misincorporated and DNA becomes

unstable

Vitamin D

Vitamin D receptor forms a

Enhances transcription of calcium

heterodimer with RXR

binding proteins

Vitamin K

Growth arrest specific gene 6

Regulates apoptosis, but it does not

product contains

interact directly with genomic

Y -carboxyglutamate residues

machinery

«-Tocopherol

Antioxidant properties.

Protects genomic machinery from free

(vitamin E)

Ameliorates damage to DNA from

radical damage. Alters activity of

excess iron. Induces two signal

protein kinase C and phospotidylinositol

transduction pathways that act at

3-kinase. This in turn regulates the

several genes, but also acts

expression of several genes . Also acts

independent of these two

on genes independent of these kinases

pathways

Calcium

Critical for intracellular signaling

Increased transcription of c-fos, c-jun,

c-myc

Iron

During deficiency, iron-regulatory

Enhances transcription of

protein binds mRNA and

metallothionein and translation of

promotes synthesis of transferrin

ferritin

receptor protein while ferritin

production is repressed. The net

effect is to increase iron utilization

Magnesium

Required for nucleic acid

Maintains fidelity of the DNA blueprint

polymerase enzyme activity

Potassium

Influences transcription of aldosterone

synthase

Selenium

Selenocysteine residue in

Helps prevent free radical damage to

glutathione peroxidase provides

genome

antioxidant properties

Zinc

Structural motif of zinc finger

Augments transcription factor binding

transcription factors

Figure 3.2. The role of vitamin B12 in (1) preventing demyelination and pernicious anemia (methyl-malonyl CoA reaction) and (2) preventing megaloblastic anemia (methionine synthase reaction).

are pregnant or planning a pregnancy should limit their intake of vitamin A to avoid the potential for birth defects as this vitamin, and its pharmacologic analogs, are considered to be teratogenic.

Vitamin A is of two types—preformed and provitamin A. Provitamin A types represent the polyphenolic carotenoids, and include a-carotene, j-carotene, y-carotene, and j-cryptoxanthine (Figure 3.4). j-carotene in particular has an important role as a free radical scavenger, and it protects DNA and membrane structures when present at an appropriate level. As this molecule is obtained from plant sources, an individual with good levels of jj -carotene is also likely to have a healthy level of many other phytonutrients that benefit the structure and function of the cell.

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