Table 4.

Biological functions and toxicities of vitamin A derivatives in vertebrates.

Appropriate Amount		Vitamin A Derivatives	Excessive Amount		Evolutionary Origin of Toxicity
Known Biochemical Basis of Functions	Examples of Biological Functions		Example of Toxicity	Biochemical Basis of Toxicity
One the least toxic retinoids; stored by binding to retinol binding proteins	Vitamin A storage and transport	Retinol (Vitamin A alcohol)	Pathological symptoms associated with hypervitaminosis A	Excessive vitamin A intake overwhelms and bypasses dedicated and specific delivery pathway to cause toxicity	Expanding biological roles of vitamin A
One the least toxic retinoids; stored as a lipid	Vitamin A storage and transport	Retinyl Ester (Vitamin A ester)	Excessive retinyl ester in the blood is toxic	Excessive retinyl esters can be converted to biologically active retinoids to cause toxicity	Expanding biological roles of vitamin A
The chromophore for opsins, the photoreceptor proteins for vision and the biological clock	Light absorption for vision and for regulating the biological clock	Retinal (Vitamin A aldehyde)	Excessive accumulation of retinal in retina causes photoreceptor degeneration	Random protein modification through Schiff-base formation; mediates photo-oxidative damage	Choice of monostable pigments that constantly release free retinal in daylight
Activates nuclear hormone receptors; regulates protein translation	Regulating the growth and differentiation from embryogenesis to adulthood; regulating learning and memory	Retinoic Acid (Vitamin A acid)	Systemic random diffusion of retinoic acid is toxic to many adult organs; also a potent teratogen	The most toxic retinoid due to its activity in activating or suppressing gene expression	Expanding biological roles of vitamin A
		A2E (Retinal Derivative)	The toxic fluorophore that accumulates in the RPE of Stargard disease patients and in aging human eyes	Photo-oxidative damage; Inhibits lysosomal enzymes and retinoid isomerase; activates the complement system	Choice of monostable pigments that constantly release free retinal in daylight