Role of Vitamin A in Human Metabolic Processes

FAO/WHO states that:

Vitamin A (retinol) is an essential nutrient needed in small amounts by humans for the normal functioning of the visual system; growth and development; and maintenance of epithelial cellular integrity, immune function, and reproduction. These dietary needs for vitamin A are normally provided for as preformed retinol (mainly as retinyl ester) and provitamin A carotenoids.

Here are the Authors' Overview of vitamin A metabolism

Authors, Blomhoff R. Vitamin A metabolism: new perspective on absorption, transport and storage. in Physiol Revs., and Parker, RS Absorption metabolism, and transport of carotenoids. in FASEB J., states in vitamin A metabolism that:

Preformed vitamin A in animal foods occurs as retinyl esters of fatty acids in association with membrane-bound cellular lipid and fat-containing storage cells. Pro-vitamin A carotenoids in foods of vegetable origin are also associated with cellular lipids but are embedded in complex cellular structures such as the cellulose-containing matrix of chloroplasts or the pigment containing portion of chromoplasts. 

Normal digestive processes free vitamin A andcarotenoids from embedding food matrices, a more efficient process from animal than from vegetable tissues. Retinyl esters are hydrolysed and the retinol and freed carotenoids are incorporated into lipid-containing, water-miscible micellar solutions. 

Products of fat digestion (e.g., fatty acids, monoglycerides, cholesterol, and phospholipids) and secretions in bile (e.g., bile salts and hydrolytic enzymes) are essential for the efficient solubilisation of retinol and especially for solubilisation of the very lipophilic carotenoids (e.g., α- and β-carotene, β-cryptoxanthin, and lycopene) in the aqueous intestinal milieu. Micellar solubilisation is a prerequisite to their efficient passage into the lipid-rich membrane of intestinal mucosal cells (i.e., enterocytes). 

To Jayarajan, P., Reddy, V. & Mohanram, M. Effect of dietary fat on absorption of β-carotene from green leafy vegetables in children. Indian in:  J. Med. Res., they explained that:

Diets critically low in dietary fat (under about 5–10 g daily) or disease conditions that interfere with normal digestion and absorption leading to steatorrhea (e.g., pancreatic and liver diseases and frequent gastroenteritis) can therefore impede the efficient absorption of retinol and carotenoids. Retinol and some carotenoids enter the intestinal mucosal brush border by diffusion in accord with the concentration gradient between the micelle and plasma membrane of enterocytes. 

Further overview  of Parker, RS.  in  FASEB J., that:

Some carotenoids pass into the enterocyte and are solubilized into chylomicrons without further change whereas some of the pro-vitamin A carotenoids are converted to retinol by a cleavage enzyme in the brush border. 

Ong, D.E. Absorption of vitamin A. In: Blomhoff R, ed. Vitamin A in Health and Disease in his overview said that:  

Retinol is trapped intracellularly by re-esterification or binding to specific intracellular binding proteins. Retinyl esters and unconverted carotenoids together with other lipids are incorporated into chylomicrons, excreted into intestinal lymphatic channels, and delivered to the blood through the thoracic duct. 

Blomhoff, R. in Physiol. Revs., continued with his overview saying that:

Tissues extract most lipids and some carotenoids from circulating chylomicrons, but most retinyl esters are stripped from the chylomicron remnant, hydrolysed, and taken up primarily by parenchymal liver cells. If not immediately needed, retinol is re-esterified and retained in the fat-storing cells of the liver (variously called adipocytes, stellate cells, or Ito cells). The liver parenchymal cells also take in substantial amounts of carotenoids. Whereas most of the body's vitamin A reserve remains in the liver, carotenoids are also deposited elsewhere in fatty tissues throughout the body. 

Meanwhile, author, Novotny, J.A., Dueker, S.R., Zech, L.A. & Clifford, A.J.  Compartmental analysis of the dynamics of β-carotene metabolism in an adult volunteer. J. Lip. Res., he stated that:

Usually, turnover of carotenoids in tissues is relatively slow, but in times of low dietary carotenoid intake, stored carotenoids are mobilised. A recent study in one subject using stable isotopes suggests that retinol can be derived not only from conversion of dietary pro-vitamin carotenoids in enterocytes – the major site of bioconversion – but also from hepatic conversion of circulating pro-vitamin carotenoids  

The quantitative contribution to vitamin A requirements of carotenoid converted to retinoids beyond the enterocyte is unknown.

Blomhoff, R. in Physiol. Revs., again stated that: 

Following hydrolysis of stored retinyl esters, retinol combines with a plasma-specific transport protein, retinol-binding protein (RBP). This process, including synthesis of the unoccupied RBP (apo-RBP), occurs to the greatest extent within liver cells but it may also occur in some peripheral tissues. The RBP-retinol complex (holo-RBP) is secreted into the blood where it associates with another hepatically synthesised and excreted larger protein, transthyretin. The transthyretin-RBP-retinol complex circulates in the blood, delivering the lipophilic retinol to tissues; its large size prevents its loss through kidney filtration. 

Stephensen, C.B.  Vitamin A is excreted in the urine during acute infection. Am. J. Clin. Nutr., gave his own statement that:

Dietary restriction in energy, proteins, and some micronutrients can limit hepatic synthesis of proteins specific to mobilisation and transport of vitamin A. Altered kidney functions or fever associated with infections (e.g., respiratory infections  

and Alvarez, J.O. Urinary excretion of retinol in children with acute diarrhea. Am. J. Clin. Nutr., continued the statement of Stephensen, C.B. in the case of diarrhoea which 
can increase urinary vitamin A loss.

According to Blomhoff, R. in Physiol. Revs., and Green, M.H. & Green, J.B.  Dynamics and control of plasma retinol. In: Blomhoff R, ed. Vitamin A in Health and Disease., 

Holo-RBP transiently associates with target-tissue membranes, and specific intracellular binding proteins then extract the retinol. Some of the transiently sequestered retinol is released into the blood unchanged and is recycled (i.e., conserved). 

Ross, C. & Gardner, E.M. The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. In: Allen L, King J., Lönnerdal B, eds. Nutrient Regulation during Pregnancy, Lactation, and Infant Growth, wrote that:

A limited reserve of intracellular retinyl esters is formed, that subsequently can provide functionally active retinol and its oxidation products (i.e., isomers of retinoic acid) as needed intracellularly. These biologically active forms of vitamin A are associated with specific cellular proteins which bind with retinoids within cells during metabolism and with nuclear receptors that mediate retinoid action on the genome. 

Chambon, P. A decade of molecular biology of retinoic acid receptors. in FASEB J., and both Pemrick, S.M., Lucas, D.A. & Grippo, J.F. The retinoid receptors in Leukemia, wrote:

Retinoids modulate the transcription of several hundreds of genes.  

Rando, R.R.  Retinoid isomerization reactions in the visual system. In: Blomhoff R, ed. Vitamin A in Health and Disease, stated that:

In addition to the latter role of retinoic acid, retinol is the form required for functions in the visual. 

Eskild, L.W. & Hansson, V.  Vitamin A functions in the reproductive organs. In: Blomhoff R, ed. Vitamin A in Health and Disease, followed with his overview over:

and reproductive systems 

and followed by the statement of Morriss-Kay, G.M. & Sokolova, N. Embryonic development and pattern formation. in FASEB J., 

 during embryonic development. 

Another Author's overview, Green, M.H. & Green, J.B. Dynamics and control of plasma retinol. In: Blomhoff R, ed. Vitamin A in Health and Disease, in his statement said that:

Holo-RBP is filtered into the glomerulus but recovered from the kidney tubule and recycled. Normally vitamin A leaves the body in urine only as inactive metabolites which result from tissue utilisation and as potentially recyclable active glucuronide conjugates of retinol in bile secretions. 

With all these authors' overview about the "the role of vitamin A in human metabolic processes, The FAO/WHO gave its statement as:

No single urinary metabolite has been identified which accurately reflects tissue levels of vitamin A or its rate of utilisation. Hence, at this time urine is not a useful biologic fluid for assessment of vitamin A nutriture.

References:

Blomhoff, R. 1991. Vitamin A metabolism: new perspectives on absorption, transport, and storage. Physiol. Revs., 71: 951–990.

Ong, D.E. 1994. Absorption of vitamin A. In: Blomhoff R, ed. Vitamin A in Health and Disease. p. 37–72. New York, Marcel Dekker, Inc.

Parker, RS. Absorption, metabolism, and transport of carotenoids. FASEB J., 1996, 10: 542–551.

Jayarajan, P., Reddy, V. & Mohanram, M. 1980. Effect of dietary fat on absorption of β-carotene from green leafy vegetables in children. Indian J. Med. Res., 71: 53–56.

Novotny, J.A., Dueker, S.R., Zech, L.A. & Clifford, A.J. 1995. Compartmental analysis of the dynamics of β-carotene metabolism in an adult volunteer. J. Lip. Res., 36: 1825–1838.

Stephensen, C.B. 1994. Vitamin A is excreted in the urine during acute infection. Am. J.

Clin. Nutr., 60: 388–392.

Alvarez, J.O. 1995. Urinary excretion of retinol in children with acute diarrhea. Am. J. Clin. Nutr., 61: 1273–1276.

Green, M.H. & Green, J.B. 1994. Dynamics and control of plasma retinol. In: Blomhoff R, ed. Vitamin A in Health and Disease. P. 119-133. New York, Marcel Dekker, Inc.

Ross, C. & Gardner, E.M. 1994. The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. In: Allen L, King J., Lönnerdal B, eds. Nutrient Regulation during Pregnancy, Lactation, and Infant Growth. P. 187-200. New York, Plenum Press.

Chambon, P. 1996. A decade of molecular biology of retinoic acid receptors. FASEB J., 10: 940–954.

Ross, A.C. & Stephensen, C.B. 1996. Vitamin A and retinoids in antiviral responses. FASEB J., 10: 979–985.

Pemrick, S.M., Lucas, D.A. & Grippo, J.F. 1994. The retinoid receptors. Leukemia. 3: S1-10.

Rando, R.R. 1994. Retinoid isomerization reactions in the visual system. In: Blomhoff R, ed. Vitamin A in Health and Disease. p.503–529. New York, Marcel Dekker, Inc.

Eskild, L.W. & Hansson, V. 1994. Vitamin A functions in the reproductive organs. In:
Blomhoff R, ed. Vitamin A in Health and Disease. p. 531–559.

Morriss-Kay, G.M. & Sokolova, N. 1996. Embryonic development and pattern formation. FASEB J., 10: 961–968.