chemistry

Retinoic acid

Retinoic acid is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Retinoic acid rather than just read about it. In short: Retinoic acid is a metabolite of vitamin A1 (all-trans-retinol) that exists in several distinct isomeric forms, including all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid. These isomers are responsible for diverse roles in biology, affecting development, male fertility, skin health and various diseases.

Key takeaways

Retinoic acid belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Retinoic acid to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Retinoic acid from memory before moving on to harder problems.

Reference excerpt

Retinoic acid is a metabolite of vitamin A1 (all-trans-retinol) that exists in several distinct isomeric forms, including all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid. These isomers are responsible for diverse roles in biology, affecting development, male fertility, skin health and various diseases. The classic isomer, all-trans retinoic acid, is required for discrete phases of embryonic development and for the production of sperm in men. The 9-cis and 13-cis isomers are less well understood as regulators of biology, and are more often researched in their drug forms as Alitretinoin and Isotretinoin, respectively. All-trans-retinoic acid (often simplified as Retinoic acid) activates the Retinoid Nuclear Receptor pathway, which is one of the 12 classic vitamin- or hormone-activated nuclear receptors. In healthy adults, clinical trials have shown that removal of all-trans-retinoic acid has a limited effect that is restricted to the initiation of spermatogenesis in men. Meanwhile, increasing the levels of all-trans-retinoic acid, such as through the use of Tretinoin, has biological effects that are not normally associated with the pathway. All-trans-retinoic acid is the major occurring retinoic acid, while isomers like 13-cis- and 9-cis-retinoic acid are also present in much lower levels. Many diseases have been associated with elevated levels of all-trans-retinoic acid, such as Type 2 Diabetes. The key role of all-trans-retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin (13-cis-retinoic acid) used for treatment of acne or retinol used for skin disorders. High oral doses of preformed vitamin A (retinyl palmitate), and all-trans-retinoic acid itself, also have teratogenic potential by this same mechanism.

Mechanism of biological action All-trans-retinoic acid acts by binding to the retinoic acid receptor (RAR), which is bound to DNA as a heterodimer with the retinoid X receptor (RXR) in regions called retinoic acid response elements (RAREs). Binding of the all-trans-retinoic acid ligand to RAR alters the conformation of the RAR, which affects the binding of other proteins that either induce or repress transcription of a nearby gene (including Hox genes and several other target genes). RARs mediate transcription of different sets of genes controlling differentiation of a variety of cell types, thus the target genes regulated depend upon the target cells. In some cells, one of the target genes is the gene for the retinoic acid receptor itself (RAR-beta in mammals), which amplifies the response. Control of retinoic acid levels is maintained by a suite of proteins that control synthesis and degradation of retinoic acid. The concentration of retinoic acid is tightly controlled and governs activation of the retinoid nuclear receptor pathway. In adults, retinoic acid is only detected at physiologically relevant levels in the testes, pancreas and immune tissues. The molecular basis for the interaction between all-trans-retinoic acid and the Hox genes has been studied by using deletion analysis in transgenic mice carrying constructs of GFP reporter genes. Such studies have identified functional RAREs within flanking sequences of some of the most 3′ Hox genes (including HOXA1, HOXB1, HOXB4, HOXD4), suggesting a direct interaction between the genes and retinoic acid. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes. In mouse studies, all-trans-retinoic acid has a supplementary role in regulating the immune response. Retinoic acid produced by dendritic cells promotes regulatory T cell formation to promote tolerance within the colon. This pathway may also be used by cancer cells to suppress the immune system. In adult humans, all-trans-retinoic acid is necessary for the process of spermatogenesis. Experiments in healthy male subjects suggests that retinoic acid is only necessary for fertility in adult humans. Retinoic acid plays a complex role in cancer. In some types of cancer cells that express retinoic acid receptors retinoic acid causes differentiation, while in other types of cancer cells that lack critical components of the retinoic acid signaling pathways retinoic acid may promote cancer progression by suppressing the immune response, and by promoting a dormant state in cancer cells whereby decreased proliferation and metabolism protects them from chemotherapy.

Biosynthesis and metabolism All-trans-retinoic acid can be produced in the body by two sequential oxidation steps that convert all-trans-retinol to retinaldehyde to all-trans-retinoic acid, but once produced it cannot be reduced again to all-trans-retinal. The enzymes that generate retinoic acid for regulation of gene expression include retinol dehydrogenase (Rdh10) that metabolizes retinol to retinaldehyde, and three types of retinaldehyde dehydrogenase, i.e. ALDH1A1 (RALDH1), ALDH1A2 (RALDH2), and ALDH1A3 (RALDH3) that metabolize retinaldehyde to retinoic acid. Enzymes that metabolize retinoic acid to turn off biological signaling include the cytochrome P450 members (CYP26). Oxidized metabolites such as 4-oxoretinoic acid are eliminated by glucuronidation in the liver.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Retinoic acid

Start with the simplest possible case. Write down what Retinoic acid claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Retinoic acid before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Retinoic acid ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Retinoic acid

In research: Retinoic acid appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Retinoic acid in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Retinoic acid is common in secondary-school and first-year university syllabi. It links to neighbouring topics Apocarotenoids, Carboxylic acids, Cell communication, so understanding it makes those chapters shorter.
In everyday life: Look for Retinoic acid outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Retinoic acid in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Retinoic acid means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Retinoic acid out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Retinoic acid in simple terms?

Why does Retinoic acid matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Retinoic acid?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Retinoic acid.