Trimethylglycine

Key takeaways

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

Reference excerpt

Trimethylglycine is an amino acid derivative with the formula (CH3)3N+CH2CO−2. A colorless, water-soluble solid, it occurs in plants. Trimethylglycine is a zwitterion: the molecule contains both a quaternary ammonium group and a carboxylate group. Trimethylglycine was the first betaine discovered; originally it was simply called betaine because it was discovered in sugar beets (Beta vulgaris subsp. vulgaris). Several other betaines are now known.

Medical uses The US Food and Drug Administration (FDA) approved betaine trimethylglycine (also known by the brand name Cystadane) for the treatment of homocystinuria, a disease caused by abnormally high homocysteine levels at birth. Specifically, the compound is indicated for the adjunctive treatment of homocystinuria, involving deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylene-tetrahydrofolate reductase (MTHFR), or cobalamin cofactor metabolism (cbl). The EU has authorized the health claim that betaine "contributes to normal homocysteine metabolism." Betaine is marketed under the brand name Cystadane. Trimethylglycine is also used as the hydrochloride salt (marketed as betaine hydrochloride or betaine HCl). Betaine hydrochloride was sold over-the-counter (OTC) as a purported gastric aid in the United States. US Code of Federal Regulations, Title 21, Section 310.540, which became effective in November 1993, banned the marketing of betaine hydrochloride as a digestive aid due to insufficient evidence to classify it as "generally recognized as safe and effective" for that specified use. The most common side effect in medical applications is elevated blood methionine levels. Trimethylglycine supplementation lowers homocysteine but also raises (given in high doses of 6g/day) LDL-cholesterol in obese individuals and renal patients.

Biological occurrence

Biosynthesis In most organisms, glycine betaine is biosynthesized by oxidation of choline. The intermediate, betaine aldehyde, is generated by the action of the enzyme mitochondrial choline oxidase (choline dehydrogenase, EC 1.1.99.1). In mice, betaine aldehyde is further oxidised in the mitochondria by the enzyme betaine-aldehyde dehydrogenase (EC 1.2.1.8). In humans betaine aldehyde activity is performed by a nonspecific cystosolic aldehyde dehydrogenase enzyme (EC 1.2.1.3) Trimethylglycine is produced by some cyanobacteria, as established by 13C nuclear magnetic resonance. It is proposed to protect for some enzymes, against inhibition by NaCl and KCl.

Osmolyte Trimethylglycine is an osmolyte, a water-soluble salt-like substance. Sugar beet was cultivated from sea beet, which requires osmolytes in order to survive the salty soils of coastal areas. Trimethylglycine also occurs in high concentrations (~10 mM) in many marine invertebrates, such as crustaceans and molluscs. It serves as a appetitive attractant to generalist carnivores such as the predatory sea slug Pleurobranchaea californica.

Methyl donor Trimethylglycine is a cofactor in methylation, a process that occurs in all mammals. Methylation is required for the biosynthesis of the neurotransmitters dopamine and serotonin, as well as for the synthesis of melatonin and coenzyme Q10. DNA methylation is also involved in epigenetics. The methylation cycle involves the remethylation of homocysteine, which occurs via either of two pathways. One pathway, present in virtually all cells, involves the enzyme methionine synthase (MS), which requires vitamin B12 as a cofactor, and also depends indirectly on folate and other B vitamins. The second pathway is restricted to the liver and kidneys in most mammals and involves betaine-homocysteine methyltransferase (BHMT), requiring trimethylglycine as a methyl donor. During normal physiological conditions, the two pathways contribute equally to removal of homocysteine in the human body. Dimethylglycine dehydrogenase also uses betaine to produce folate, contributing back to methionine synthase. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms such as mutations in the MS gene.

Human use Trimethylglycine is used as a supplement for both animals and plants. Processing sucrose from sugar beets yields glycine betaine as a byproduct. The economic significance of trimethylglycine is comparable to that of sugar in sugar beets. Betaine is commercially important for the poultry industry. It prevents coccidiosis, which costs billions of dollars annually. Salmon farms apply trimethylglycine to relieve the osmotic pressure on the scales when workers transfer the fish from freshwater to saltwater. Betaine is not needed when sufficient dietary choline is present for synthesis. When insufficient betaine is available, elevated homocysteine levels and decreased SAM levels in blood occur. Supplementation of betaine in this situation would resolve these blood marker issues, but not compensate for other functions of choline.

In foods

Trimethylglycine is a popular dietary supplement for athletes. In 2017, the European Food Safety Authority concluded that betaine was safe "as a novel food to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet." Trimethylglycine supplementation may cause diarrhea, bloating, cramps, dyspepsia, nausea or vomiting. Although rare, it can also cause excessive increases in serum methionine concentrations in the brain, which may lead to cerebral edema, a life-threatening condition.

Biochemistry The addition of betaine to polymerase chain reactions improves the amplification of DNA by reducing the formation of secondary structure in GC-rich regions. The addition of betaine may enhance the specificity of the polymerase chain reaction by eliminating the base pair composition dependence of DNA melting.

References

External links USDA Database for the Choline Content of Common Foods – including the data on choline metabolites, such as betaine, in 434 food items.

Illustrations

Worked examples

Example 1 — a first encounter with Trimethylglycine

Start with the simplest possible case. Write down what Trimethylglycine 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 Trimethylglycine 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 Trimethylglycine 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 Trimethylglycine

In research: Trimethylglycine 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 Trimethylglycine 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: Trimethylglycine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Alpha-Amino acids, Amino acid derivatives, Food additives, so understanding it makes those chapters shorter.
In everyday life: Look for Trimethylglycine 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.

How to study Trimethylglycine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Trimethylglycine 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 Trimethylglycine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Trimethylglycine in simple terms?

Trimethylglycine is an amino acid derivative with the formula (CH3)3N+CH2CO−2. A colorless, water-soluble solid, it occurs in plants.

Why does Trimethylglycine 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 Trimethylglycine?

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 Trimethylglycine.