Betaine

Betaine is also known as trimethylamine, and is the quaternary ammonium derivatives of glycine and a class of N-methyl-compound or trimethyl inner salt after the hydrogen of the amino group being substituted by the methyl group. Common kinds include glycyl betaine, β-alanyl-betaine and prolyl-betaine. We can obtain prismatic crystals or leaf-shaped crystals from ethanol, is sweet taste, and deliquescent. Melting point: 293 °C; it will decomposed at 300 °C. It is soluble in water, methanol and ethanol, but insoluble in ether, and can be isomerized into dimethylamino methyl acetate at the melting point. We can obtain its monohydrate crystal from the aqueous solution of the free acid HO-N (CH3) 3-CH2COOH which generates betaine upon dehydration at 100 °C, and is stable in acid. It can obtain trimethylamine upon reaction with concentrated aqueous potassium hydroxide and can have Maillard reaction with sugar (browning reaction). It is presented in plant such as cottonseed and beetroot as well as in animal substance such as barbed shark meat and crab refined juice. It can be recycled from the mother liquor of beet sugar. It may also be obtained from the methylation reaction of amino acetate or the reaction between chloroacetate with trimethylamine. Clinically it is used in combination with N-amidino glycine for treatment of myasthenia gravis. In analytic chemistry, it can also be used as the reagent for identifying gold. This product is the amphoteric surfactants of betaine used as a leveling agent for vat dyes dying. Drought or salt stress, many plants can accumulate betaine inside their body and become a major organic solutes for osmotic adjustment and have a further protective effect on cell membrane and cellular proteins.
The above information is edited by the Chemicalbook of Dai Xiongfeng.

Betaine is a natural compound, and belonging to a kind of quaternary ammonium alkaloids. The name of this substance is because of that it is first extracted from sugar beet. It has been over 50 years since it has been used as a feed additive. It has attracted much attention due to its important of in protein metabolism and lipid metabolism of animals, and has been widely applied. Adding to the chicken feed can increase the amount of broiler carcass quality and chest quantity and also improve the food palatability and utilization rate. Increased feed intake and daily gain is the main component of palatability of aquatic attractant. It can also improve the feed rate of piglet, and thus promoting its growth. It has another important feature as a kind of osmotic pressure regulator which can alleviate the stress of gastrointestinal and increase the viability of juvenile shrimp and fish seedlings under the variation of various stress conditions, such as: cold, heat, disease, and weaning in living conditions. Betaine has a protective effect on the stability of VA and VB and can further improve their application efficacy without having the irritation effect of betaine hydrochloride at the same time.

Betaine is widely presented in plants and animals with beet containing the highest content among plants. In animal body, betaine is acted as a highly active methyl donor which plays a important role in regulating the metabolism of methyl group, and can partially substitute the methionine and choline, and thus promoting fat metabolism, improving feed palatability, alleviating heat stress, regulating the osmotic pressure of the body, and maintaining the stability of the vitamin premix for improving farming efficiency.
Inside animal bodies, betaine provide methyl group to cysteine, generating methionine which is further converted into S-adenosine methionine, and further transferring methyl group then to DNA, RNA, protein, creatine, lipids and other important methyl-containing ingredients. Methyl group is very unstable and can’t be synthesized by animals themselves but can only rely on food supply. The efficiency of betaine of providing methyl group is 1.2 times as high as choline chloride, and 3.8 times as high as methionine. Choline itself can’t act as a methyl donor which must be first transported to the mitochondria for oxidation into betaine and finally released into the cytoplasm before being able to act as a methyl donor. Betaine also has effects on prevention and treatment of fatty liver of pigs, chickens and fish.

It is colorless crystals or white crystalline powder, odorless, and has a sweet taste. Melting point: 293 °C (decomposition). It is highly deliquescent. 1g of this product can be dissolved in 0.63 g of water, 1.8g of methanol, and 11.5g of ethanol. It is slightly soluble in ether. Concentrated alkaline can lead to its decomposition and release of trimethylamine. Male rats: orally LD50:11.2g/kg, female rats by oral LD50:11.15g/kg.

1. Adding betaine to the feed has protective effects on the vitamins contained in the feed, also makes feed be tolerable to high temperature and can subject to long-term storage, and thus greatly improving feed utilization rate as well as reducing the costs. Adding 0.05% betaine to the chicken feed can substitute 0.1% methionine; adding betaine to the bait have palatability effect on both fishes and shrimp, thus betaine can be used as the swelling agent of aquatic product in large amount. Adding betaine to the pig feed added betaine can increase the appetite of pigs and increase the rate of lean meat. 1kg Betaine is equivalent to 3.5kg of methionine. The ability to provide methyl of betaine is 1.2 times as strong as that of choline chloride, and 3.8 times as strong as that of methionine with a very significant feed efficiency.
2. It is used as betaine type amphoteric surfactants, also used as leveling agent of dye vat dyes.
3. It can be used as feed grade anhydrous betaine for being as a feed additive. It is a natural and efficient methyl donor which can partially substitute methionine and choline chloride, lower the feed costs, reduce back-fat of pig, and increase the rate lean meat and carcass quality.
4. It can be used for lowering blood pressure, anti-fatty liver and anti-aging.
5. It can be used as a feed additive for promoting animal growth and increased disease resistance.

It is recycled from beet sugar mother liquor, and can also be used for synthetic production.
1. Extraction method. The mother liquor of beet sugar contains 12%-15% of the betaine, which can directly used for recycle. Heat 300 parts of the mother liquor to 50 °C, add 80 parts of calcium chloride, stir and filter while hot for a certain time. The filtrate was acidified with hydrochloric acid after cooling for crystallization at 20-30 °C, after separation, dry to obtain 30 parts of betaine.
2. Synthesis method through the quaternization between chloroacetate and trimethylamine.
Use 16% sodium hydroxide solution for neutralization of 195 parts of 48.6% aqueous solution of chloroacetate into sodium chloroacetate and then mix with 360 parts of 16.4% trimethylamine for ventilation at 50 °C for 1h, then ventilate at 80 °C for 1 h. The reaction was diluted and further adhered by ion exchange resin (Dowex-50-8) with ammonia elution to obtain the betaine solution. It further undergoes vacuum concentration and crystallization to obtain the final product.

Betaine is a natural compound extracted from Beta vulgaris, widely present in both leaves and roots. Within plants, betaine is synthesised through a two-step oxidation of choline within chloroplasts. The first step converts choline into betaine aldehyde, a rate-limiting step catalysed by choline monooxygenase. The second step converts betaine aldehyde to betaine, catalysed by betaine aldehyde dehydrogenase ^[1]. It possesses certain pharmacological activities and may be employed to treat deficiencies or defects in specific enzymes leading to hyperhomocysteinemia in blood and urine. This medication facilitates the removal of excess homocysteine from the body.

[1] TAKABE T, TANAKA Y, TAKABE T. CHAPTER 2:Betaine in Sugar Beet[C]. 2015: 0. DOI:10.1039/9781782628446-00009.

White crystalline powder; bland aroma.

betaine is a surfactant, humectant, and excellent skin conditioner. It is also used to build product viscosity and as a foam booster. It is found mostly in skin cleansers, shampoos, and bath products.

Betaine is an active ingredient in toothpaste to control the symptoms of dryness of the mouth. It is used to treat homocystinuria, which is a defect in the major pathway of methionine biosynthesis. It is also used for boosting the immune system and for improving athletic performance. It is helpful to prevent noncancerous tumors in the colon (colorectal adenomas).

ChEBI: The amino acid betaine derived from glycine.

Betaine also called trimethylglycine or N,N,N triethylammonium acetate, is an analog of glycine with three methyl groups. It is highly compatible with polymerase chain reaction (PCR) buffer mixture. Betaine is a PCR enhancing reagent that is widely used for improving the yield and specificity of PCR products, especially during the PCR amplification of targets rich in GC content or those that form secondary structures resulting in poor yield. Betaine facilitates DNA strand separation and manages the DNA melting temperature (Tm) difference between the GC and AT pairs in DNA. It stabilizes the ds DNA by equalizing the contribution of GC- and AT-base pairs. Betaine has been broadly used to optimize multiplex and ‘long and accurate′ polymerase chain reaction (LA-PCR). The addition of 1.0-1.7 M aqueous betaine to a PCR mixture has been reported to reduce the base pair composition dependence on DNA strand melting.

End-product of oxidative metabolism of choline, betaine is a general methyl donor, in particular in a minor pathway of methionine biosynthesis. It is used to treat homocystinuria, which is a defect in the major pathway of methionine biosynthesis.

Crystallise betaine from aqueous EtOH or EtOH/Et2O. The monohydrate loses H2O above 100o. Betaine undergoes internal alkylation to methyl dimethylaminoacetate Purification of Biochemicals — Amino Acids and Peptides above its melting point. It is also prepared by treating the hydrochloride (below) with silver oxide and recrystallising from EtOH/Et2O. [Edsall J Am Chem Soc 66 1767 1943, Leifer & Lippincott J Am Chem Soc 79 5098 1957, for pK see Grob et al. Chem and Ind (London) 1222 1955, Beilstein 4 III 1127, 4 IV 2369.]

[1] Patent: CN104557579, 2017, B. Location in patent: Paragraph 0013; 0024; 0025; 0026; 0027; 0028; 0029-0053
[2] Journal of the American Chemical Society, 2005, vol. 127, # 50, p. 17954 - 17961
[3] Chemical Communications, 2013, vol. 49, # 63, p. 7076 - 7078
[4] Analytical Chemistry, 2013, vol. 85, # 23, p. 11464 - 11470