Vitamin B6 is a collective term for all vitamin-active derivatives of 3-hydroxy-2-methypyridine.The individual pyridine derivatives are distinguished by their different substituents on the fourth carbon atom – C4. The substituents are methyl hydroxy groups, aldehyde residues or methyl amino groups. Accordingly, a distinction is made between the alcohol pyridoxine or pyridoxol (PN), the aldehyde pyridoxal (PL) and the amide pyridoxamine (PM).PN, PL and PM can be phosphorylated at their fifth carbon atom – C5 – to give pyridoxine-5́-phosphate (PNP), pyridoxal-5́-phosphate (PLP) and pyridoxamine-5́-phosphate (PMP). All 6 derivatives are metabolically convertible into each other and exhibit the same vitamin activities.The 5́-phosphoric acid esters PLP and PMP are the actual biologically active forms. They perform their functions in the organism in the form of coenzymes and are essential for many enzymatic reactions.The main degradation product is 4-pyridoxic acid (4-PA), which is formed from pyridoxal and has no known metabolic function.
Occurrence, stability, and availability
Vitamin B6 is almost ubiquitously distributed and is found in foods of both plant and animal origin.Pyridoxine is found primarily in plant foods, whereas pyridoxal, pyridoxamine, and their phosphoric acid esters are present primarily in animal foods.Pyridoxine, which is found in plants, is relatively heat stable, resulting in only minor losses – up to 20% – during processing of plant foods. Pyridoxal and pyridoxamine, on the other hand, are heat labile. Thus, the cooking and leaching losses of PL, PM and their phosphoric acid esters in meat, for example, are about 30 to 45 %. In the case of milk, vitamin B6 losses of up to 40% are to be expected due to sterilization and drying processes.The vitamin B6 derivatives, especially those from animal foods, are extremely sensitive to daylight or UV light. If milk is stored in clear glass bottles, the vitamin B6 content can be reduced by 50 % within a few hours as a result of exposure to sunlight.Despite careful handling of the food, average vitamin B6 losses of 20 % must be expected.The availability of the B vitamers depends primarily on their binding form. In foods from plant sources, such as soybeans, white bread, and orange juice, vitamin B6 is partially present – 0 to 50% – bound to glucose, as a glycosylate – pyridoxine-5́-beta-D-glycoside.Heat treatment, UV irradiation, and low-moisture storage of certain plant foods lead to reactions between vitamin B6 and reducing sugars, such as glucose, increasing the glycosylate content up to 82% [6,7]. In addition, reductive binding of pyridoxal and pyridoxal-5́-phosphate to proteins can occur. This binding occurs via the delta-amino groups of the lysine residues of the proteins. Such resulting derivatives, such as delta-pyridoxylysine, are biologically inactive and may even exhibit anti-vitamin B6 activity.Binding to reducing sugars and proteins or amino acids impairs the bioavailability of vitamin B6. Consequently, glycosylates and protein-bound B6 vitamers have an absorption rate of only 50-60% compared to free pyridoxine.No pyridoxine glycosides are detectable in foods of animal origin. Thus, vitamin B6 from animal foods has a higher bioavailability than from plant foods.Intestinal bacteria are able to synthesize vitamin B6 and increase the available amount of pyridoxine. Gastrointestinal tract diseases decrease bacterial vitamin B6 synthesis. In addition, due to damaged transport mechanisms in the mucosa (mucous membrane of the small intestine) or lack of enzyme systems, the bioavailability or absorption of vitamin B6 is significantly reduced.Diuresis – increased urinary excretion by the kidneys – and intake of dietary fiber also results in reduced pyridoxine availability. During diuresis, vitamin B6 is increasingly lost in the urine due to its water solubility. This is similar for dietary fiber.Due to their ability to form a gel – the “cage effect” – dietary fiber deprives vitamin B6 of absorption and eliminates it from the organism via the kidneys.Furthermore, vitamin B6 interacts with pharmaceuticals. For example, tuberculostatics, such as isoniazid, increase renal excretion of vitamin B6 and at the same time form a hydrazone complex that leads to inactivation of the vitamin.Similarly, oral contraceptives – birth control pills -, antihypertensives, such as hydralazine, and penicillamine decrease the available amount of vitamin B6.
Absorption
Vitamin B6 ingested with food is absorbed throughout the small intestine, especially in the jejunum – empty intestine. In order to be absorbed into the enterocytes (cells of the small intestinal mucosa or mucosa), the B6 vitamers bound to phosphate or glucose must first be hydrolyzed by nonspecific phosphatases or glucosidases in the intestinal lumen. In this process, the phosphate and glucose residues are cleaved from the B6 derivatives by reaction with water. In free, unbound form, pyridoxine, pyridoxal, and pyridoxamine then enter enterocytes in a non-saturable, passive mechanism. The absorption rate is estimated to be 70-75%.In enterocytes, PN, PL, and PM are phosphorylated at C5 by catalysis under the influence of zinc-dependent pyridoxalkinase. This rephosphorylation has the purpose of retention of vitamin B6 forms in the organism – metabolic trapping.Before the B6 derivatives are released into the blood at the basolateral membrane of enterocytes, dephosphorylation occurs again.
Transport and storage
Absorbed vitamin B6 enters the liver via the portal vein but may also be transported via the bloodstream to peripheral tissues, such as muscle. In the hepatocytes (liver cells) or cells of peripheral tissues, there is immediate phosphorylation of PN, PL and PM and subsequent formation of the metabolically active form pyridoxal-5́-phosphate. For this purpose, a phosphate group is added to PN, PL and PM in a first step with the help of the zinc-dependent pyridoxalkinase, resulting in PNP, PLP and PMP. In a second step, vitamin B2-dependent pyridoxine phosphate oxidase leads to the oxidation of PNP and PMP, synthesizing pyridoxal-5́-phosphate.Through a variety of transaminases, PLP and PMP can be reversibly converted into each other intracellularly. Re-dephosphorylation of PNP to PN, PLP to PL, and PMP to PM by phosphatases is also possible.Vitamin B6 vitamers are released from hepatocytes as well as cells of peripheral tissues into the bloodstream.In blood plasma, over 90% of total vitamin B6 is present as pyridoxal and pyridoxal phosphate. Plasma PLP is derived exclusively from the liver. The transport of PL and PLP in the blood occurs on the one hand in connection with albumin, and on the other hand in the erythrocytes (red blood cells). While PLP in erythrocytes is mostly bound to the N-terminal valine of the beta-chain of hemoglobin, except to PLP-dependent enzymes, PL is associated with the N-terminal valine of the alpha-chain of hemoglobin.In contrast to PL and PLP, pyridoxine and 4-pyridoxic acid are freely present in blood plasma. For this reason, PN and 4-PA are readily glomerular filterable in the kidneys and can be rapidly eliminated in the urine.To re-enter peripheral tissues from the bloodstream, the phosphorylated B6 derivatives must be hydrolyzed by alkaline phosphatases in plasma for release from this complex. The B6 vitamers can only penetrate the cell membrane in their dephosphorylated form. Intracellularly, a phosphate group is again attached to them by zinc-dependent pyridoxalkinases. PNP and PMP are subsequently converted for the most part to the actual active form PLP.In various tissues and organs, especially in the musculature, PLP is involved as a coenzyme in numerous enzymatic reactions.The total body stock of vitamin B6, predominantly in the form of pyridoxal-5́-phosphate, amounts to about 100 mg with an adequate supply and is distributed between the musculature and liver. 80% of the PLP retinated in the body is found bound to glycogen phosphorylase in the muscles. The remaining B6 is stored in the liver. Only 0.1% is found in the blood plasma.Finally, enzyme-bound pyridoxal-5́-phosphate represents the most important storage form for vitamin B6.
Degradation and excretion
In the liver and also to a lesser extent in the kidneys, the phosphate group of nonenzyme-bound pyridoxal-5́-phosphate is cleaved by a phosphatase. The resulting pyridoxal undergoes irreversible conversion to the biologically ineffective vitamin B6 form 4-pyridoxic acid under the influence of vitamin B2-dependent aldehyde oxidase and vitamin B3-dependent aldehyde dehydrogenase.4-PA is the major degradation product and the main excretion form in the metabolism of vitamin B6. The acid is eliminated via the kidneys in the urine.When vitamin B6 intake is particularly high, other vitamin B6 compounds in nonphosphorylated forms, such as PN, PL, and PM, are also excreted renally.
