Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 23 Vitamins
Stellate cells
Chylomicrons
Vacuoles
β-Carotene
Retinyl esters
Parenchymal Cells
Retinol
Retinal
Retinoic Acid
Oxidation
Disposal
Vacuoles
Vacuoles
Retinyl Esters
β-Carotene
Retinyl Esters
β-Carotene
Retinol
Retinal
Retinol Binding Protein
Retinoic Acid
Oxidation
Disposal
Retinol
Retinal
Retinol Binding Protein
Retinoic Acid
Oxidation
Disposal
Retinol Binding Protein
+
Transerythrin
Retinol Binding Protein
+
Transerythrin
Retinol Binding Protein
Transerythrin
Retinol Binding Protein
Transerythrin
Target Tissues
FIGURE 23-5 Steps in vitamin A processing in liver Stellate and parenchymal cells. Retinoids and carotenoids are transported from the intestine in
chylomicron particles and are cleared primarily by the liver. The stellate cell is designed to sequester lipid-like compounds until needed. Fluids in the
liver sinusoids derived from blood and lymph bathe stellate cells. The stellate cells are in communication with liver parenchymal cells. As the body
needs vitamin A, retinyl esters and β -carotene sequestered in lipid vacuoles are released and eventually converted to retinol. The next steps involve the
binding of vitamin A to retinol-binding protein (RBP). When released into circulation, RBP exists as a complex not only with vitamin A but also with
another protein, transthyretin, which binds thyroxin. The RBP and the transthyretin complex transport not only vitamin A but also thyroxins to targeted
cells. The primary target cells for vitamin A are epithelial in nature (e.g., fetal epidermal cells, the cells of the gastrointestinal mucosa, reproductive
tract, pulmonary secretory cells, and salivary gland).
cells but are associated with specific binding proteins. The
binding to and release from such proteins is rapid. Because
the binding proteins are contiguously associated as a part
of the cellular scaffolding, it is possible for given retinoid
metabolites to move vectorially along given paths to specific
locations in the cell.
Regarding the retinoid metabolites, retinoic acid is the
most important, serving as a ligand for nuclear receptors
( Velazquez and Fernendez-Mejia, 2004 ; Velazquez et al.,
2005 ). These receptors are a part of a family of transcription
factors that include nuclear receptors that also interact
with glucorticoids, thyroxin, and the so-called peroxisomal
proliferation activator agonists or ligands. Retinoic acid
influences the transcriptional regulation of at least 600
known genes. Both excesses and deficiencies of vitamin A
can markedly influence the expression.
The catabolism of excess retinal may be initiated by
one of several alcohol dehydrogenase isozymes with subsequent
oxidation via peroxisomal enzymes. Microsomal
enzymes (cytochrome P450 hydroxylases) are also
involved. Examples of some of some of the events and
products are given in Figure 23-6 . Important interactions
involve agents that can induce cytochrome P450 hydroxylases
(or monooxygenases). For example, phenobarbital
can cause depletion of liver retinol by induction of a microsomal
oxidase system that promotes retinoid oxidation.
4 . Functions
The major roles of vitamin A are in cellar differentiation,
tissue growth, and vision. In vision, vitamin A, as a component
of rhodopsin, facilitates the efficient transfer of energy