Vitamin a

Vitamin A is a collective name for a group of fat-soluble vitamins with a polyterpene structure. The substances are either absorbed directly with food or are formed in the organism from carotenes (provitamin A).

In humans, retinal (aldehyde), retinol (all-trans-retinol, alcohol; also known as vitamin A1), retinoic acid(tretinoin, unsaturated monocarboxylic acid) and retinyl palmitate (ester compound of retinol and palmitic acid) belong to the vitamin A group. Furthermore, "3-dehydroretinol" (also known as vitamin A2), a derivative of retinal, belongs to the vitamin A group. Compared to vitamin A1, the molecule is characterized by an additional double bond between C3 and C4.

Chemically, all members of the vitamin A group are retinoid derivatives. The various members of the vitamin A group can be converted into each other by enzymatically catalysed reactions.

Vitamin A1: The biologically most important representative of the vitamin A group is the alcoholic compound "all-trans-retinol" or also called vitamin A1. Vitamin A1 is an unsaturated alcohol with the molecular formula C20H30 O which is insoluble in water but readily soluble in ethanol, ether and fatty oils. Vitamin A1 is heat stable, but is destroyed by oxygen, oxidizing substances, UV rays and acids.

Vitamin A2: Vitamin A2 is called 3-dehydroretinol (derivative of all-trans-retinol), a dehydrated compound with an additional conjugated double bond between C3 and C4 of the molecule (see retinol formula).

Retinyl palmitate: Vitamin A is found in the animal organism mainly in its free alcoholic form (retinol), but also in ester form, bound to higher molecular fatty acids, especially palmitic acid (retinyl palmitate). Retinol and its palmitic acid ester (retinyl palmitate) are ingested with animal food. In contrast, retinal (aldehyde) and retinoic acid do not play a role in nutrition. In the intestinal mucosa, retinol binds directly to the cell membrane of enterocytes. Retinyl palmitate is hydrolysed in the intestine by pancreatic lipase into retinol and palmitic acid.

Carotenoids: The carotene derivatives found in plants (especially beta-carotene, alpha-carotene, beta-cryptoxanthin) are absorbed with plant food. The carotenes are cleaved in the intestine by the enzyme beta-carotene-15,15′-monooxygenase (BMO) to form retinal (in the case of beta-carotene these are 2 molecules retinal). In the cytosol, vitamin A (retinal and also retinol) binds to several "retinol-binding proteins RBPs). The "plasma retinol-binding protein" RBP4, is a 21 kDa transporter of all-trans-retinol (retinol), which circulates in plasma together with free retinol. RBP4 is synthesized primarily in the liver, but also in fatty tissue (Perduca M et al. 2018) and seems to play the most important biological role in RBPs.

SAA, an RBP: Little is known about the RBPs that ensure increased retinol transport during infection. Thus, in infections, serum amyloid A (SAA), which is highly regulated in the liver, plays a role as an additional retinol-binding protein (Derebe MG et al. 2014).

Vitamin A (retinol) is absorbed by the body with food and transported to the liver by cellular retinol-binding proteins (CRBP I-III). The enzyme retinol dehydrogenase converts retinol into vitamin A aldehyde, the retinal, by oxidation. In a further step, the retinal dehydrogenase oxidizes this to retinoic acid. Retinoic acid can exist in various naturally occurring stereoisoforms, such as all-trans-retinoic acid, 9-cis-retinoic acid (9-cisRA) and 13-cis-retinoic acid (13-cisRA). At the target cell it binds to the RBP receptor.

The organism is only able to break down excess vitamin A to a small extent. Retinol/retinal is temporarily stored in the tissue, especially in the liver as retinyl palmitate. This process also takes place in various mammals. Pig liver, for example, contains up to 42mg vitamin A (140,000 IU) per 100 g. The liver of polar bears contains particularly large amounts of vitamin A. Polar bear liver is therefore toxic (hypervitaminosis) when consumed in large quantities.

The precursor of vitamin A, provitamin A, is also known as beta-carotene. Retinoids, which can activate RXR and RAR, play an essential role in embryological development, cell growth and cell differentiation. They also have the ability to induce apoptosis. It has been shown that RXR antagonists can prevent retinoid-induced apoptosis triggering in acute promyelocytes leukemia cells.

Vitamin A plays an important role in the act of vision. Vitamin A aldehydes are involved in the formation of rhodopsin, the light-sensitive dye of the eye. Vitamin A plays a central role in other physiological processes. It is required for embryogenesis, cell proliferation and differentiation, immune regulation and glucose and lipid metabolism.

Further physiological functions of vitamin A are performed by the "vitamin A acid". This acid is able to activate the transcriptional network via specific receptors called retinoic acid receptors (RARs)/retinoid-X receptors(RXRs). The liver plays a decisive role in vitamin A metabolism. Among other things, the liver produces retinol-binding protein 4 (RBP4). Furthermore, as a storage organ, it ensures the homeostasis of vitamin A. Chronic liver diseases, especially cirrhosis and liver fibrosis, can lead to a disruption of vitamin A metabolism and to a vitamin A deficit (Saeed A et al. 2017).

Vitamin A acid(tretinoin), is of particular importance for the function and division of the epidermis. It is also needed for the synthesis of testosterone. The essential importance of vitamin A and its derivatives for the epidermis and for its skin appendages has led to its development into the substance group of retinoids. Retinoids are of great importance in the local and systemic treatment of acne, psoriasis. They are also effective in the prophylaxis and therapy of epithelial and lymphatic skin tumours.

Too much vitamin A during pregnancy is also harmful to the development of the fetus. Increased doses of vitamin A have a teratogenic effect. Malformations can be caused by oral, but also intraperitoneal and subcutaneous vitamin A intake. Oral administration of 13-cisRA for the treatment of acne or psoriasis during the 2nd-5th week p.c. results in severe congenital malformations, which are summarized under the term retinoic acid embryopathy (RAE) (Lammer EJ et al. 1985). Craniofascial malformations are characteristic of retinoic acid embryopathy.

Retinoic acids have a long half-life. They are stored in fatty tissue. Retinoic acids continue to have teratogenic effects after the end of therapy. Therefore, patients must not become pregnant months after the end of regular vitamin A supplementation. The teratogenic side effects are caused by the activation of the heterodimer RXR/RARβ, of which RARβ has a greater influence than RXR (Mark M et al. 2006).

One International Unit (IU) corresponds to 0.3ug of Vitamin A alcohol. 1g of vitamin A corresponds to 3.33 million IU. The daily requirement is 0.8mg (2,700 IU) for children and 0.8-1.0mg (2,700-3,300 IU) for adults.

S.a. vitamin A deficiency (= Phrynoderm), vitamin A hypervitaminosis.

Fetal vitamin A loss syndrome (VAD syndrome) can lead to defects in the cardiovascular, respiratory and skeletal systems and cause defects in the urogenital tract and kidney hypoplasia (Takahashi YI et al. 1975). In addition, VAD syndrome can result in blindness of the newborn. The pleiotropic congenital malformations resulting from VAD syndrome illustrate the far-reaching effects of vitamin A on embryonic development.

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