BACKGROUND

Vitamins are organic substances that are essential for several enzymatic functions in human metabolism Thiamine was discovered in 1912 & was thought to be a vital amine compound & thus the term vitamin was invented

VITAMINS
Vitamins are classified according to solubility into fat soluble & water soluble. 13 vitamins are known, 4 fat soluble (KEDA) & 9 water soluble (C, Folate & the B group).

13 Vitamines

4 Fat soluble

9 Water soluble

B Group

Folate

VITAMIN A
Ancient Egyptians recognized that night blindness could be treated by consumption of liver.
In the late 1920s, through the efforts of a Swiss scientist named Karrer and his colleagues, the fat-soluble compound in liver was isolated and termed vitamin A.

VITAMIN A
Vitamin A is a generic term for many related compounds. Retinol (alcohol), Retinal (aldehyde) are often called preformed vitamin A. Retinal can be converted by the body to retinoic acid which is known to affect gene transcription. Body can convert b-carotene to retinol, thus called provitamin A.

CHEMISTRY
Vitamin A is a subclass of a family of lipidsoluble compounds referred to as retinoic acids. There are two main forms of vitamin A: 1. Provitamin A carotenoids (betacarotene and others), and 2. Preformed vitamin A. Provitamin A carotenoids are found in plants. There are many forms of provitamin A, but beta-carotene is only one that is metabolized by mammals into vitamin A.

CHEMISTRY

Preformed vitamin A i.e

retinol, retinoic

retinal,

acid, and retinyl esters)

is the most active form of vitamin A; mostly found in animal sources of food and is also the form supplied by most supplements.

Some supplements provide a combination of provitamin A (beta-carotene) and preformed vitamin A.

SOURCES

The common food sources of preformed vitamin A (retinols) are liver, kidney, egg yolk, and butter. Provitamin A (beta-carotene) is mostly found in green leafy vegetables.

Clinical significance:
Because

vitamin A from animal sources or supplements is preformed, it is more likely to cause toxicity than the provitamin A from plant sources.

METABOLISM

The initial steps in metabolism depend on the type of vitamin A ingested. The metabolism of provitamin A (beta-carotene) into active vitamin A is a highly regulated step, so excessive intake of vitamin A from plant sources is very unlikely to cause toxicity. By contrast, absorption and storage of preformed vitamin A is efficient, and toxicity can occur if excessive quantities are ingested.

METABOLISM

Provitamin A must be cleaved to retinal before absorption. This step is subject to feedback regulation, which depends on vitamin A status. Preformed vitamin A is hydrolyzed into retinol in the lumen of the small intestine. A number of enzymes are involved in this process at the level of the mucosal brush-border. These steps are highly efficient and not subject to

feedback regulation.

METABOLISM

Within the small intestine, retinols are reesterified into retinyl-esters incorporated into chylomicrons excreted into lymphatics and plasma.
In the blood, chylomicrons broken down into multiple remnants including apolipoproteins B and E, which contain retinol esters.

METABOLISM

The apolipoproteins taken up by the liver via a receptor-mediated endocytosis on the surface of the hepatocytes, and retinol esters are released. Retinol Binding Proteins (RBP) storage in vitamin A-containing lipid globules within the hepatic stellate cells.

further metabolized combine with

METABOLISM

About 50 to 85 percent of the total body retinol is stored in the liver. It is also found in many other tissues in much smaller concentrations. In order for vitamin A to reach its target organs, it binds to RBP molecules for release into

plasma as a retinol-RBP

complex.

Intake intestinal fat absorption brush border metabolism apolipoprotein take up by liver metabolize and combine with RBP store in the liver binds to RBP molecules

reach target organ (as retinol-RBP complex).

Reach target organ (as retinol-RBP cplx

Intake

Binds to RBP molecules

Intestinal

fat absorption

Store in the liver

Metabolize and combine with RBP

Brush border metabolism

Apolipoprotein take up by liver