Understanding vitamin B6 and its role

Understanding vitamin B6 and its role
12 min read
17 August 2022

Vitamin B 6 (VB 6 ) is a group of nitrogen-containing compounds with similar properties, including three derivatives of  pyridoxine  (PN), pyridoxal (PL) and pyridoxamine (PM). Pyridoxal and pyridoxamine are mainly found in animal foods in their phosphorylated forms, while pyridoxine is mainly found in plant foods. These three derivatives have the same biological activity and can be converted into each other. Now synthetic vitamin B6 is generally  pyridoxine hydrochloride. Various enzyme systems containing vitamin B6 coenzymes are involved in the metabolism of many nitrogen-containing compounds (such as proteins, lipids) and the process of glycogen catabolism, especially in the biosynthesis and catabolism of essential amino acids and non-essential amino acids. . Therefore, the physiological function of vitamin B6 is mainly involved in the metabolism of transamination, decarboxylation, amino meso, tryptophan and unsaturated fatty acids in the form of coenzyme. 

Almost all foods containing B vitamins contain vitamin B6. Rice bran, wheat bran and sunflower seeds are rich sources of vitamin B6, followed by bananas, corn, fish, lean meat, liver, kidney, soybeans, etc. The recommended dose of vitamin B6 is 2 mg/d for adults and 2.5 mg/d for pregnant and lactating women. The needs of children and adolescents vary at different stages: infants need about 0.3 to 0.4 mg/d, and children aged 7 to 9 need about 1.25 mg/d. The requirement of vitamin B6 has a certain relationship with the intake of protein. When the intake of protein increases, the requirement of vitamin B6 should also increase. About 1.75 to 2 mg of vitamin B6 is required for every 100g of protein intake. 【Vitamin B 6】 The basic molecular structure of the three kinds of natural vitamin B6 is 2-methyl-3-hydroxy-5-hydroxymethylpyridine, the difference is that the groups on the 4th carbon position are hydroxymethyl, formyl and aminomethyl respectively . The hydroxymethyl group on the 5th carbon position of each natural vitamin B6 can be phosphorylated, and the active coenzyme forms are pyridoxal 5'-phosphate (PLP) and pyridoxal 5'-phosphate. Amine (pyridoxamine 5'-phosphate, PMP). Vitamin B6 is easily soluble in water and alcohol, and slightly soluble in fat solvents. In acidic solution, the three kinds of vitamin B6 are relatively stable to heat, but when heated in alkaline solution, pyridoxal is easily destroyed. In the solution, the three kinds of vitamin B6 are more sensitive to light, especially when exposed to ultraviolet light. Pyridoxal and pyridoxal 5'-phosphate can react with free amino groups in solution to form Schiff bases, especially pyridoxal 5'-phosphate is more likely to react with amino groups to form Schiff bases due to its structural characteristics . The absorption site of vitamin B6 is mainly in the jejunum. Vitamin B6 in food mainly exists in the form of PN, PLP and PMP. Among them, PLP and PMP in animal food must be hydrolyzed into PL and PM by non-specific phosphatase in the small intestine. Therefore, the absorption forms of vitamin B6 in the small intestine are mainly PN, PL and PM. The absorption method is mainly a passive absorption process that is not saturable, and the absorption speed is fast and the absorption rate is high. After a large dose (such as 10 mg or more) of PLP is ingested, PLP can be slowly absorbed without hydrolysis. 

Molecular forms of vitamin B6 interconvert 

Vitamin B6 is mainly transported in plasma and red blood cells. After the intestinal mucosa absorbs PN, most of it enters the blood circulation in the form of PN, and about 30% of the PN is phosphorylated in the small intestinal mucosa and enters the blood stream in the form of pyridoxine 5'-phosphate (PNP). After human administration of PN, its plasma PL can be increased by 12 times, and PLP is increased even more. The sum of both plasma PL and PLP accounts for more than 90% of the total plasma vitamin B6. Both PL and PLP are combined with albumin in plasma, and PLP is closely combined with albumin. Therefore, although PLP accounts for more than 60% of the total plasma vitamin B6, it is not easily utilized by tissue cells; It can be taken up by tissue cells and is the main form of transport in plasma. PN and PL can enter red blood cells by diffusion, and form PLP under the action of PL kinase, and then combine with hemoglobin. PL can also be directly combined with valine at the end of the α chain of hemoglobin, and accumulate in red blood cells. Its concentration in red blood cells can be 4 to 5 times that of plasma. Therefore, PL may also be a transport of vitamin B6 in red blood cells. way, but the exact role that red blood cells play in the transport of vitamin B6 is unclear. In the liver, PN, PL and PM are converted into their respective phosphorylated forms by pyridoxal kinase (PL kinase) with the participation of Zn and ATP, and then PNP and PMP can be converted into their respective phosphorylated forms by flavin mononucleotide oxidase ( FMN oxidase) is converted to PLP; in the liver, PLP and other 5'-phosphate forms can be hydrolyzed to free forms by alkaline phosphatase; in tissues, PL is converted to PLP by NAD as a coenzyme Catalytically oxidized to form an irreversible metabolic end product, pyridoxic acid (PA), which is excreted in urine. 

The liver is an active tissue for vitamin B6 metabolism and regulation, and its metabolism and regulation of vitamin B6 are manifested in the following aspects: The liver is the main organ for the conversion of dietary vitamin B6 into PLP. Under physiological conditions, the activities of PL kinase and alkaline phosphatase in the liver are similar to ensure a dynamic balance between the free and phosphorylated forms of vitamin B6. Aldehyde oxidase (with FAD as coenzyme) in the liver is sufficient to oxidize excess PL to the metabolic end product pyridoxine. As a product, PLP can feedback inhibit the activity of FMN oxidase and regulate the conversion process of PMP and PNP into PLP. The metabolism and regulation of vitamin B6 by the liver can not only ensure the need of PLP in target tissues, maintain the normal level of vitamin B6 in plasma, but also prevent excessive accumulation of PLP in the liver. 

Liver stores and metabolizes vitamin B6 Circulating vitamin B6 can diffuse into the muscles and be stored in the liver. The total metabolic pool of vitamin B6 in the human body is estimated to be 1000 μmol, and 80% to 90% is present in the muscle. Most of the vitamin B6 exists in the form of PLP combined with glycogen phosphorylase, which accounts for 5% of muscle soluble protein. %, through the conversion of muscle protein, vitamin B6 can be decomposed to meet the minimum requirements of the body. In comparison, the total amount of vitamin B6 in the blood circulation is less than 1 μmol, and the renewal is very slow, which is estimated to take 25 to 33 days. Pyridoxine (PA) is the main metabolic end product of vitamin B6. The liver is the main organ for the formation of PA. In the liver, PL produces PA through the action of aldehyde oxidase. In other tissues, PL can also form a small amount of PA under the catalysis of NAD-requiring aldehyde dehydrogenase. The PA formed in the body is mainly excreted from the urine, and the excretion accounts for about 40% to 60% of the intake. In addition to PA, there are a small amount of PN, PL and pyridoxine in the urine, which accounts for about 40% of the intake of vitamins. 10% of the total amount of B6. The excretion and excretion form of vitamin B6 in urine are mainly regulated by the intake of vitamin B6, but have no obvious relationship with the storage capacity in the body. When a physiological dose of vitamin B6 is ingested, most of it is excreted in the form of PA at 3 hours; when the intake of PN exceeds 10 mg, the excretion of PA in urine accounts for a decrease in the proportion of intake, while the relative excretion of PN The amount increases; after a large dose of oral vitamin B6, within 36 hours, most of it is excreted in the form of vitamin B6 prototype. Vitamin B6 is involved in various metabolic processes Vitamin B6 is enzymatically phosphorylated in vivo to form its coenzyme form, pyridoxal 5′-phosphate (PLP), which is involved in more than sixty enzyme-catalyzed reactions. The functional group on the PLP molecule is -HCO on the 4th carbon position, which is easy to form an unstable intermediate with the amino group of the amino acid - a Schiff base. After molecular rearrangement, the H on the α-carbon atom of the amino acid is removed. Then, the Schiff base isomer is formed, which is a stable resonance structure with conjugated double bonds. Under the joint action of specific enzyme molecules, various chemical reactions can be carried out on the α-carbon atom. Several main types of enzymatic reactions involved in PLP include: ① Transamination: Participate in the transamination process of amino acids such as alanine, asparagine, arginine, cysteine, isoleucine, lysine, etc. . ②Decarboxylation: Participate in the decarboxylation process of tryptophan, tyrosine, histidine, and dopa. ③Side chain decomposition: Participate in the aldol splitting reaction of hydroxyl-containing amino acids and the cystathionine splitting process of sulfur-containing amino acids. ④ Racemization: such as the conversion process of D-amino acid and L-amino acid in bacteria. Involvement in gluconeogenesis: PLP is involved in the production of glucose through its role in transaminases and glycogen phosphorylases. Affects niacin formation: PLP affects the conversion of tryptophan to niacin by participating in the action of kynureninase. Affect lipid metabolism: As a coenzyme of serine palmitoyltransferase, it is involved in the biosynthesis of sphingomyelin; the nutritional status of vitamin B6 can affect the synthesis of carnitine and the metabolism of essential fatty acids in the body. Effects on the nervous system: PLP is involved in the metabolism of serotonin, dopamine, histamine, taurine, norepinephrine and γ-aminobutyric acid, and affects the synthesis of neurotransmitters. Lack of vitamin B6 can lead to a series of clinical symptoms such as affective disorders, abnormal EEG, cognitive decline in the elderly, abnormal movement and epilepsy in infants and young children, and decreased learning and memory ability during growth. Effects on nucleic acid synthesis: PLP participates in the metabolism of one-carbon units through its role in serine transhydroxymethylase, thereby affecting nucleic acid synthesis; it can inhibit thymidine nucleotide synthase and affect DNA synthesis. Immunity effects: In animals and humans, vitamin B6 nutritional status has been found to be associated with cell-mediated immune responses, possibly affecting tumor growth and indicators of immune function in asymptomatic HIV-1-infected individuals. Hormone regulation: In recent years, studies have shown that the effects of several steroid hormones are regulated by PLP. PLP can bind to the second site of steroid receptors and change the binding of steroid receptors to DNA, thereby reducing the effect of steroids. Vitamin B6 may be associated with some endocrine diseases, because it has been found that the regulation of cytosolic aspartate aminotransferase gene expression by PLP is through the binding of the glucocorticoid receptor to the glucocorticoid-like response element to inactivate the receptor of. 

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Li Wangqian 2
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