Retinol

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Retinol
All-trans-Retinol2.svg
Retinol 3D balls.png
Retinol
Clinical data
AHFS/Drugs.com Monograph
License data
Routes of
administration 		By mouth, intramuscular [1]
Drug class vitamin
ATC code
Legal status
Legal status
Identifiers
  • (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.621 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H30O
Molar mass 286.459 g·mol−1
3D model (JSmol)
Melting point 62–64 °C (144–147 °F)
Boiling point 137–138 °C (279–280 °F) (10−6 mm Hg)
Solubility in water 0.000017 [2]  mg/mL (20 °C)
  • OC/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)/CCCC1(C)C
  • InChI=1S/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13+
  • Key:FPIPGXGPPPQFEQ-OVSJKPMPSA-N

Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family that is found in food and used as a dietary supplement. [3] Retinol or other forms of vitamin A are needed for vision, cellular development, maintenance of skin and mucous membranes, immune function and reproductive development. [3] Dietary sources include fish, dairy products, and meat. [3] As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia. [1] It is taken by mouth or by injection into a muscle. [1] As an ingredient in skin-care products, it is used to reduce wrinkles and other effects of skin aging. [4]

Contents

Retinol at normal doses is well tolerated. [1] High doses may cause enlargement of the liver, dry skin, and hypervitaminosis A. [1] [5] High doses during pregnancy may harm the fetus. [1] The body converts retinol to retinal and retinoic acid, through which it acts. [3]

Retinol was discovered in 1909, isolated in 1931, and first made in 1947. [6] [7] It is on the World Health Organization's List of Essential Medicines. [8] Retinol is available as a generic medication and over the counter. [1] In 2021, vitamin A was the 298th most commonly prescribed medication in the United States, with more than 500,000 prescriptions. [9] [10]

Medical uses

Retinol is used to treat vitamin A deficiency.

Three approaches may be used when populations have low vitamin A levels: [11]

  1. Through dietary modification involving the adjustment of menu choices of affected persons from available food sources to optimize vitamin A content.
  2. Enriching commonly eaten and affordable foods with vitamin A, a process called fortification. It involves addition of synthetic vitamin A to staple foods like margarine, bread, flours, cereals, and infant formula during processing.
  3. By giving high-doses of vitamin A to the targeted deficient population, a method known as supplementation. In regions where deficiency is common, a single large dose is recommended to those at high risk twice a year. [12]

Retinol is also used to reduce the risk of complications in measles patients. [12]

Side effects

The Recommended Daily Intake (RDA) for preformed supplemental vitamin A for adult men and women is 900 and 700 Retinol Activity Units(RAE)/day, respectively, or about 3,000 IU and 2,300 IU. [3] In pregnancy, the vitamin A RDA is 750–770 RAE/day (about 2,500–2,550 IU). [3] During lactation, the RDA increases to 1,200–1,300 RAE/day (about 4,000–4,300 IU, with differences depending on age). [3]

Retinol Activity Units can only be converted to IU (International Units) when the source of the vitamin A is known. [3] The IU values listed above do not apply to food sources of vitamin A. [3]

Too much vitamin A in retinoid form can be harmful. The body converts the dimerized form, carotene, into vitamin A as it is needed, so high levels of carotene are not toxic, whereas the ester (animal) forms are. The livers of certain animals, especially those adapted to polar environments, such as polar bears and seals, [13] often contain amounts of vitamin A that would be toxic to humans. Thus, vitamin A toxicity is typically reported in Arctic explorers and people taking large doses of synthetic vitamin A. The first documented death possibly caused by vitamin A poisoning was that of Xavier Mertz, a Swiss scientist, who died in January 1913 on an Antarctic expedition that had lost its food supplies and fell to eating its sled dogs. Mertz may have consumed lethal amounts of vitamin A by eating the dogs' livers. [14]

Vitamin A acute toxicity occurs when a person ingests vitamin A in large amounts more than the daily recommended value in the threshold of 25,000 IU/kg or more. Often, the patient consumes about 3–4 times the RDA's specification. [15] Toxicity of vitamin A is believed to be associated with the methods of increasing vitamin A in the body, such as food modification, fortification, and supplementation, all of which are used to combat vitamin A deficiency. [16] Toxicity is classified into two categories: acute and chronic. The former occurs a few hours or days after ingestion of a large amount of vitamin A. Chronic toxicity takes place when about 4,000 IU/kg or more of vitamin A is consumed for a long time. Symptoms of both include nausea, blurred vision, fatigue, weight-loss, and menstrual abnormalities. [17]

Excess vitamin A is suspected to be a contributor to osteoporosis. This seems to happen at much lower doses than those required to induce acute intoxication. Only preformed vitamin A can cause these problems, because the conversion of carotenoids or retinyl esters into vitamin A is downregulated when physiological requirements are met; [18] but excessive uptake of carotenoids can cause carotenosis.

Excess preformed vitamin A during early pregnancy is associated with a significant increase in birth defects. [19] These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects. [20] The FDA recommends that pregnant women get their vitamin A from foods containing beta carotene and that they ensure that they consume no more than 5,000 IU of preformed vitamin A (if any) per day. Although vitamin A is necessary for fetal development, most women carry sufficient stores of vitamin A in their liver cells, [21] so over-supplementation should be strictly avoided.

A review of all randomized controlled trials in the scientific literature by the Cochrane Collaboration published in JAMA in 2007 found that supplementation with beta carotene or vitamin A increased mortality by 5% and 16%, respectively. [22] This effect has been attributed to the role of retinol and retinoic acid in increasing circulating cholesterol and triglycerides as well as promoting cancer incidence. [23]

Studies emerging from developing countries India, Bangladesh, and Indonesia strongly suggest that, in populations in which vitamin A deficiency is common and maternal mortality is high, dosing expectant mothers with retinol can greatly reduce maternal mortality. [24] Similarly, dosing newborn infants with 50,000 IU (15 mg) of vitamin A within two days of birth can significantly reduce neonatal mortality. [25] [26]

Biological roles

Retinol or other forms of vitamin A are needed for eyesight, maintenance of the skin, and human development. [1] Other than for vision, which requires 11-cis retinal, the active compound is retinoic acid, synthesized from retinal, in turn synthesized from retinol. The differing biological roles of retinoic acid depend on its stereochemistry and whether it is present in the all-trans, 9-cis or 13-cis forms. [27]

Embryology

Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos. During development, there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond to retinoic acid differently depending on the amount present. For example, in vertebrates, the hindbrain transiently forms eight rhombomeres and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead, rhombomeres 1–4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Homeobox (Hox) genes that encode different homeodomain transcription factors which in turn can turn on cell type specific genes. [28] Deletion of the Homeobox (Hox-1) gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2. Retinoic acid is not required for patterning of the retina as originally proposed, but retinoic acid synthesized in the retina is secreted into surrounding mesenchyme where it is required to prevent overgrowth of perioptic mesenchyme which can cause microphthalmia, defects in the cornea and eyelid, and rotation of the optic cup. [29]

Stem cell biology

Synthetic retinoic acid is used in differentiation of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways. It is thought to initiate differentiation into a number of different cell lineages through activation of the Retinoic acid receptor. It has numerous applications in the experimental induction of stem cell differentiation; amongst these are the differentiation of human embryonic stem cells to posterior foregut lineages. [28]

Vision

Retinol is an essential compound in the cycle of light-activated chemical reactions called the "visual cycle" that underlies vertebrate vision. Retinol is converted by the protein RPE65 within the pigment epithelium of the retina into 11-cis-retinal. This molecule is then transported into the retina's photoreceptor cells (the rod or cone cells in mammals) where it binds to an opsin protein and acts as a light-activated molecular switch. When 11-cis-retinal absorbs light it isomerizes into all-trans-retinal. The change in the shape of the molecule in turn changes the configuration of the opsin in a cascade that leads to the neuronal firing, which signals the detection of light. [30] The opsin then splits into the protein component (such metarhodopsin) and the cofactor all-trans-retinal. The regeneration of active opsin requires conversion of all-trans-retinal back to 11-cis-retinal via retinol. The regeneration of 11-cis-retinal occurs in vertebrates via conversion of all-trans-retinol to 11-cis-retinol in a sequence of chemical transformations that occurs primarily in the pigment epithelial cells. [31]

Without adequate amounts of retinol, regeneration of rhodopsin is incomplete and night blindness occurs. Night blindness, the inability to see well in dim light, is associated with a deficiency of vitamin A, a class of compounds that includes retinol and retinal. In the early stages of vitamin A deficiency, the more light-sensitive and abundant rods, which have rhodopsin, have impaired sensitivity, and the cone cells are less affected. The cones are less abundant than rods and come in three types, each contains its own type of iodopsin, the opsins of the cones. The cones mediate color vision, and vision in bright light (day vision).

Glycoprotein synthesis

Glycoprotein synthesis requires adequate vitamin A status. In severe vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction. [32]

Immune system

Vitamin A is involved in maintaining a number of immune cell types from both the innate and acquired immune systems. [33] These include the lymphocytes (B-cells, T-cells, and natural killer cells), as well as many myelocytes (neutrophils, macrophages, and myeloid dendritic cells). Vitamin A maintains immune barriers in the gut through its activity as retinoic acid. [34]

Skin

Deficiencies in vitamin A have been linked to an increased susceptibility to skin infection and inflammation. [35] Vitamin A appears to modulate the innate immune response and maintains homeostasis of epithelial tissues and mucosa through its metabolite, retinoic acid (RA). As part of the innate immune system, toll-like receptors in skin cells respond to pathogens and cell damage by inducing a pro-inflammatory immune response which includes increased RA production. [35] The epithelium of the skin encounters bacteria, fungi and viruses. Keratinocytes of the epidermal layer of the skin produce and secrete antimicrobial peptides (AMPs). Production of AMPs resistin and cathelicidin, are promoted by RA. [35] Another way that vitamin A helps maintain a healthy skin and hair follicle microbiome, especially on the face, is by reduction of sebum secretion, which is a nutrient source for bacteria. [35] Retinol has been the subject of clinical studies related to its ability to reduce the appearance of fine lines on the face and neck. [4] [36]

Red blood cells

Vitamin A may be needed for normal red blood cell formation; [37] [38] deficiency causes abnormalities in iron metabolism. [39] Vitamin A is needed to produce the red blood cells from stem cells through retinoid differentiation. [40]

Units of measurement

When referring to dietary allowances or nutritional science, retinol is usually measured in international units (IU). IU refers to biological activity and therefore is unique to each individual compound, however 1 IU of retinol is equivalent to approximately 0.3 micrograms (300 nanograms).

Nutrition

Vitamin properties
Solubility Fat
RDA (adult male)900 μg/day
RDA (adult female)700 μg/day
RDA upper limit (adult male)3,000 μg/day
RDA upper limit (adult female)3,000 μg/day
Deficiency symptoms
Excess symptoms
Common sources

This vitamin plays an essential role in vision, particularly night vision, normal bone and tooth development, reproduction, and the health of skin and mucous membranes (the mucus-secreting layer that lines body regions such as the respiratory tract). While Vitamin A is often considered to be an antioxidant that prevents cancers, it does not have antioxidant activity [41] and is shown to promote the development of many cancers. [42] [43]

There are two sources of dietary vitamin A. Retinyl ester or retinol forms, which are immediately available to the body or carotene precursors, also known as provitamins, which must be converted to active forms by the body. These are obtained from fruits and vegetables containing yellow, orange and dark green pigments, known as carotenoids, the most well-known being β-carotene. [44] For this reason, amounts of vitamin A are measured in Retinol Equivalents (RE). One RE is equivalent to 0.001 mg of retinol, or 0.006 mg of β-carotene, or 3.3 International Units of vitamin A.

Vitamin A is fat-soluble and is stored in the liver and fat tissue. [45] When required by a particular part of the body, the liver releases some vitamin A, which is carried by the blood and delivered to the target cells and tissues. [46]

Dietary intake

The Dietary Reference Intake (DRI) Recommended Daily Amount (RDA) for vitamin A for a 25-year-old male is 900 micrograms/day, or 3000 IU. National Health Service daily recommended values are slightly lower at 700 micrograms for men and 600 micrograms for women. [47]

During the absorption process in the intestines, retinol is incorporated into chylomicrons as the ester form, and it is these particles that mediate transport to the liver. Liver cells store vitamin A as the ester, and when retinol is needed in other tissues, it is de-esterifed and released into the blood as the alcohol. Retinol then attaches to a serum carrier, retinol binding protein, for transport to target tissues. [48] A binding protein inside cells, cellular retinoic acid binding protein, serves to store and move retinoic acid intracellularly.

Deficiency

Prevalence of vitamin A deficiency in 1995 Vitamin A deficiency.PNG
Prevalence of vitamin A deficiency in 1995

Vitamin A deficiency is common in developing countries but rarely seen in developed countries. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A. [49] Vitamin A deficiency in expecting mothers increases the mortality rate of children shortly after childbirth. [50] Night blindness is one of the first signs of vitamin A deficiency. Vitamin A deficiency contributes to blindness by depleting the necessary form needed for rhodopsin. [31]

Sources

Retinoids are found naturally only in foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75–7 oz (50–198 g):

Chemistry

Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a trans or cis configuration of four of the five double bonds found in the polyene chain. The cis isomers are less stable and can readily convert to the all-trans configuration (as seen in the structure of all-trans-retinol shown at the top of this page). Nevertheless, some cis isomers are found naturally and carry out essential functions. For example, the 11-cis-retinal isomer is the chromophore of rhodopsin, the vertebrate photoreceptor molecule. Rhodopsin is composed of the 11-cis-retinal covalently linked via a Schiff base to the opsin protein (either rod opsin or blue, red or green cone opsins). The process of vision relies on the light-induced isomerisation of the chromophore from 11-cis to all-trans resulting in a change of the conformation and activation of the photoreceptor molecule. [31]

Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating nuclear retinoic acid receptors. [29] The non-visual functions of vitamin A are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal vitamin A in their diet.

Synthesis

Biosynthesis

Vitamin A biosynthesis Chem 157 vitamin a synthesis project.png
Vitamin A biosynthesis

Retinol is synthesized from the breakdown of β-carotene. First, the β-carotene 15,15'-monooxygenase cleaves β-carotene at the central double bond, creating an epoxide. This epoxide is then attacked by water creating two hydroxyl groups in the center of the structure. The cleavage occurs when these alcohols are oxidized to the aldehydes using NADH. This compound is called retinal. Retinal is then reduced to retinol by the enzyme retinol dehydrogenase. Retinol dehydrogenase is an enzyme that is dependent on NADH. [52]

Industrial synthesis

b-ionone ring Ionone beta.svg
β-ionone ring

Retinol is made industrially via total synthesis using either a method developed by BASF [53] [54] or a Grignard reaction utilized by Hoffman-La Roche. [55] The two major suppliers, DSM and BASF, are believed to use total synthesis. [56]

The world market for synthetic retinol is primarily for animal feed, leaving approximately 13% for a combination of food, prescription medication and dietary supplement use. [56] The first industrialized synthesis of retinol was achieved by the company Hoffmann-La Roche in 1947. In the following decades, eight other companies developed their own processes. β-ionone, synthesized from acetone, is the essential starting point for all industrial syntheses. Each process involves elongating the unsaturated carbon chain. [56] Pure retinol is extremely sensitive to oxidization and is prepared and transported at low temperatures and oxygen-free atmospheres. When prepared as a dietary supplement or food additive, retinol is stabilized as the ester derivatives retinyl acetate or retinyl palmitate. Prior to 1999, three companies, Roche, BASF and Rhone-Poulenc controlled 96% of global vitamin A sales. In 2001, the European Commission imposed total fines of 855.22 Euros on these and five other companies for their participation in eight distinct market-sharing and price-fixing cartels that dated back to 1989. Roche sold its vitamin division to DSM in 2003. DSM and BASF have the major share of industrial production. [56]

History

Frederick Gowland Hopkins, 1929 Nobel Prize for Physiology or Medicine Frederick Gowland Hopkins nobel.jpg
Frederick Gowland Hopkins, 1929 Nobel Prize for Physiology or Medicine
George Wald, 1967 Nobel Prize for Physiology or Medicine George Wald nobel.jpg
George Wald, 1967 Nobel Prize for Physiology or Medicine

In 1912, Frederick Gowland Hopkins demonstrated that unknown accessory factors found in milk, other than carbohydrates, proteins, and fats were necessary for growth in rats. Hopkins received a Nobel Prize for this discovery in 1929. [57] One year later, Elmer McCollum, a biochemist at the University of Wisconsin–Madison, and colleague Marguerite Davis identified a fat-soluble nutrient in butterfat and cod liver oil. Their work confirmed that of Thomas Burr Osborne and Lafayette Mendel, at Yale, also in 1913, which suggested a fat-soluble nutrient in butterfat. [58] The "accessory factors" were termed "fat soluble" in 1918 and later "vitamin A" in 1920. In 1931, Swiss chemist Paul Karrer described the chemical structure of vitamin A. [57] Retinoic acid and retinol were first synthesized in 1946 and 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens. [59] [60]


In 1967, George Wald was a co-recipient of the Nobel Prize in Physiology and Medicine "..."for their discoveries concerning the primary physiological and chemical visual processes in the eye." [61] Photoreceptor cells in the eye contain a chromophore composed of the protein opsin and 11-cis retinal. When struck by light, 11-cis retinal undergoes photoisomerization to all-trans retinal and via signal transduction cascade send a nerve signal to the brain. The all-trans retinal is reduced to all-trans retinol and travels back to the retinal pigment epithelium to be recycled to 11-cis retinal and conjugated to opsin. [62]

Although vitamin A was not confirmed as an essential nutrient and a chemical structure described until the 20th century, written observations of conditions created by deficiency of this nutrient appeared much earlier in history. Sommer classified historical accounts related to vitamin A and/or manifestations of deficiency as follows: "ancient" accounts; 18th- to 19th-century clinical descriptions (and their purported etiologic associations); early 20th-century laboratory animal experiments, and clinical and epidemiologic observations that identified the existence of this unique nutrient and manifestations of its deficiency. [24]

Related Research Articles

<span class="mw-page-title-main">Vitamin A</span> Essential nutrient

Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most notably β-carotene (beta-carotene). Vitamin A has multiple functions: growth during embryo development, maintaining the immune system, and healthy vision. For aiding vision specifically, it combines with the protein opsin to form rhodopsin, the light-absorbing molecule necessary for both low-light and color vision.

Orthomolecular medicine is a form of alternative medicine that claims to maintain human health through nutritional supplementation. It is rejected by evidence-based medicine. The concept builds on the idea of an optimal nutritional environment in the body and suggests that diseases reflect deficiencies in this environment. Treatment for disease, according to this view, involves attempts to correct "imbalances or deficiencies based on individual biochemistry" by use of substances such as vitamins, minerals, amino acids, trace elements and fatty acids. The notions behind orthomolecular medicine are not supported by sound medical evidence, and the therapy is not effective for chronic disease prevention; even the validity of calling the orthomolecular approach a form of medicine has been questioned since the 1970s.

In visual physiology, adaptation is the ability of the retina of the eye to adjust to various levels of light. Natural night vision, or scotopic vision, is the ability to see under low-light conditions. In humans, rod cells are exclusively responsible for night vision as cone cells are only able to function at higher illumination levels. Night vision is of lower quality than day vision because it is limited in resolution and colors cannot be discerned; only shades of gray are seen. In order for humans to transition from day to night vision they must undergo a dark adaptation period of up to two hours in which each eye adjusts from a high to a low luminescence "setting", increasing sensitivity hugely, by many orders of magnitude. This adaptation period is different between rod and cone cells and results from the regeneration of photopigments to increase retinal sensitivity. Light adaptation, in contrast, works very quickly, within seconds.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

<span class="mw-page-title-main">Retinal</span> Vitamin A aldehyde, a polyene chromophore

Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).

<span class="mw-page-title-main">Retinoid</span> Group of tetraterpenes

The retinoids are a class of chemical compounds that are natural derivatives of vitamin A or are chemically related to it. Synthetic retinoids are used in medicine where they regulate skin health, immunity and bone disorders.

<span class="mw-page-title-main">Xerophthalmia</span> Dry eye

Xerophthalmia is a medical condition in which the eye fails to produce tears. It may be caused by vitamin A deficiency, which is sometimes used to describe that condition, although there may be other causes.

<span class="mw-page-title-main">Retinyl palmitate</span> Vitamin A chemical compound

Retinyl palmitate, or vitamin A palmitate, is the ester of retinol (vitamin A) and palmitic acid, with formula C36H60O2. It is the most abundant form of vitamin A storage in animals.

<span class="mw-page-title-main">Hypervitaminosis A</span> Toxic effects of ingesting too much vitamin A

Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A. Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history. Toxicity results from ingesting too much preformed vitamin A from foods, supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount.

Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. It is generally accepted that doses of any vitamin greatly in excess of nutritional requirements will result either in toxicity or in the excess simply being metabolised; thus evidence in favour of vitamin supplementation supports only doses in the normal range. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful; several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent.

<span class="mw-page-title-main">Retinoic acid</span> Metabolite of vitamin A

Retinoic acid (simplified nomenclature for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that is required for embryonic development, male fertility, regulation of bone growth and immune function. All-trans-retinoic acid is required for chordate animal development, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. In adult tissues, the activity of endogenous retinoic acid appears limited to immune function. and male fertility. Retinoic acid administered as a drug (see tretinoin and alitretinoin) causes significant toxicity that is distinct from normal retinoid biology.

<span class="mw-page-title-main">Carotenoid oxygenase</span>

Carotenoid oxygenases are a family of enzymes involved in the cleavage of carotenoids to produce, for example, retinol, commonly known as vitamin A. This family includes an enzyme known as RPE65 which is abundantly expressed in the retinal pigment epithelium where it catalyzed the formation of 11-cis-retinol from all-trans-retinyl esters.

<span class="mw-page-title-main">Vitamin A deficiency</span> Disease resulting from low Vitamin A concentrations in the body

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia is one of the first signs of VAD, as the vitamin has a major role in phototransduction; but it is also the first symptom that is reversed when vitamin A is consumed again. Xerophthalmia, keratomalacia, and complete blindness can follow if the deficiency is more severe.

The visual cycle is a process in the retina that replenishes the molecule retinal for its use in vision. Retinal is the chromophore of most visual opsins, meaning it captures the photons to begin the phototransduction cascade. When the photon is absorbed, the 11-cis retinal photoisomerizes into all-trans retinal as it is ejected from the opsin protein. Each molecule of retinal must travel from the photoreceptor cell to the RPE and back in order to be refreshed and combined with another opsin. This closed enzymatic pathway of 11-cis retinal is sometimes called Wald's visual cycle after George Wald (1906–1997), who received the Nobel Prize in 1967 for his work towards its discovery.

In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction

Vitamins occur in a variety of related forms known as vitamers. A vitamer of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.

<span class="mw-page-title-main">Lecithin retinol acyltransferase</span> Mammalian protein found in Homo sapiens

Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene.

<span class="mw-page-title-main">Emixustat</span> Chemical compound

Emixustat is a small molecule notable for its establishment of a new class of compounds known as visual cycle modulators (VCMs). Formulated as the hydrochloride salt, emixustat hydrochloride, it is the first synthetic medicinal compound shown to affect retinal disease processes when taken by mouth. Emixustat was invented by the British-American chemist, Ian L. Scott, and is currently in Phase 3 trials for dry, age-related macular degeneration (AMD).

<span class="mw-page-title-main">Retinol-binding protein</span> Family of proteins that bind retinol

Retinol-binding proteins (RBP) are a family of proteins with diverse functions. They are carrier proteins that bind retinol. Assessment of retinol-binding protein is used to determine visceral protein mass in health-related nutritional studies.

In general, cognitive support diets are formulated to include nutrients that have a known role in brain development, function and/or maintenance, with the goal of improving and preserving mental processes such as attentiveness, short-term and long-term memory, learning, and problem solving. Currently, there is very little conclusive research available regarding cat cognition as standardized tests for evaluating cognitive ability are less established and less reliable than cognitive testing apparatus used in other mammalian species, like dogs. Much of what is known about feline cognition has been inferred from a combination of owner-reported behaviour, brain necropsies, and comparative cognitive neurology of related animal models. Cognition claims appear primarily on kitten diets which include elevated levels of nutrients associated with optimal brain development, although there are now diets available for senior cats that include nutrients to help slow the progression of age-related changes and prevent cognitive decline. Cognition diets for cats contain a greater portion of omega-3 fatty acids, especially docosahexaenoic acid (DHA) as well as eicosapentaenoic acid (EPA), and usually feature a variety of antioxidants and other supporting nutrients thought to have positive effects on cognition.

References

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  2. ↑ Bonrath W, Gao B, Houston P, McClymont T, Müller MA, Schäfer C, et al. (September 2023). "75 Years of Vitamin A Production: A Historical and Scientific Overview of the Development of New Methodologies in Chemistry, Formulation, and Biotechnology". Organic Process Research & Development. 27 (9): 1557–84. doi: 10.1021/acs.oprd.3c00161 . ISSN   1083-6160.
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