Pyridoxal 5′-phosphate (PLP) the metabolically active form of vitamin B6
Vitamin B6 is one of the B vitamins, and thus an essential nutrient.
Vitamin B6 refers to a group of six chemically similar compounds (vitamers), which can be interconverted in biological systems.
Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.
Plants synthesize pyridoxine as a means of protection from the UV-B radiation found in sunlight
and for the role it plays in the synthesis of chlorophyll.
Humans cannot synthesize any of the various forms of the vitamin, and hence must obtain it via diet, either of plants, or of other animals.
There is some absorption of the vitamin produced by intestinal bacteria, but this is not sufficient to meet dietary needs.
For adult humans, recommendations are in the range of 1.0 to 2.0 milligrams (mg) per day.
Ill effects from intakes that are too high, so a set safe upper limit ranging from as low as 25 mg/day to as high as 100 mg/day depending on the country.
Beef, pork, fowl and fish are generally good sources; dairy, eggs, mollusks and crustaceans also contain vitamin B6, but at lower levels.
There is enough B6 in a wide variety of plant foods so that a vegetarian/vegan diet does not put consumers at risk for deficiency.
Dietary deficiency of vitamin B6 is rare.
Classic clinical symptoms of B6 deficiency include: rash and inflammation around the mouth and eyes, plus neurological effects that include drowsiness and peripheral neuropathy affecting sensory and motor nerves in the hands and feet.
Vitamin B6 deficiency can be the result of anti-vitamin drugs.
Rare genetic defects can trigger vitamin B6 deficiency-dependent epileptic seizures in infants, responsive to pyridoxal 5′-phosphate therapy.
Vitamin B6 is a water-soluble vitamin.
The vitamin actually comprises a group of six chemically related compounds, i.e., vitamers, that all contain a pyridine ring as their core.
These are pyridoxine, pyridoxal, pyridoxamine, and their respective phosphorylated derivatives pyridoxine 5′-phosphate, pyridoxal 5′-phosphate and pyridoxamine 5′-phosphate.
Pyridoxal 5′-phosphate has the highest biological activity.
The other vitamers are convertible to that form.
Vitamin B6 serves as a co-factor in more than 140 cellular reactions, mostly related to amino acid biosynthesis and catabolism, but is also involved in fatty acid biosynthesis and other physiological functions.
Pyridoxine hydrochloride is the form most commonly given as vitamin B6 dietary supplement.
Pyridoxine phosphate is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression.
Pyridoxine phosphate serves as a coenzyme for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion.
Transaminases break down amino acids with PLP as a cofactor,
And proper activity of these enzymes is crucial for the process of moving amine groups from one amino acid to another.
PLP is required for the conversion of tryptophan to niacin, so low vitamin B6 status impairs this conversion.
PLP is a cofactor in the biosynthesis of five important neurotransmitters: serotonin, dopamine, epinephrine, norepinephrine, and gamma-aminobutyric acid.
PLP is a required coenzyme of glycogen phosphorylase, the enzyme necessary for glycogenolysis.
Glycogen is a carbohydrate storage molecule, primarily found in muscle, liver and brain.
Glycogen breakdown frees up glucose for energy.
PLP also catalyzes transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis, the biosynthesis of glucose.
PLP is an essential component of enzymes that facilitate the biosynthesis of sphingolipids, particularly, the synthesis of ceramide.
The breakdown of sphingolipids is also dependent on vitamin B6 because sphingosine-1-phosphate lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP-dependent.
PLP aids in the synthesis of hemoglobin, by serving as a coenzyme for the enzyme aminolevulinic acid synthase.
PLP binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin.
PLP can increase or decrease the expression of certain genes.
Increased intracellular levels of the vitamin lead to a decrease in the transcription of glucocorticoids.
Vitamin B6 deficiency leads to the increased gene expression of albumin mRNA.
PLP influences expression of glycoprotein IIb by interacting with various transcription factors; the result is inhibition of platelet aggregation.
Isoniazid side effect include numbness in the hands and feet, also known as peripheral neuropathy, and Co-treatment with vitamin B6 alleviates the numbness.
Overconsumption of seeds from Ginkgo biloba can deplete vitamin B6.
The ginkgotoxin is a vitamin antagonist.
Symptoms include vomiting and generalized convulsions.
Ginkgo seed poisoning can be treated with vitamin B6.
Recommended Dietary Allowances (RDAs), expressed as milligrams per day, increase with age from 1.2 to 1.5 mg/day for women and from 1.3 to 1.7 mg/day for men.
The RDA for pregnancy is 1.9 mg/day, for lactation, 2.0 mg/day.
For children ages 1–13 years the RDA increases with age from 0.5 to 1.0 mg/day.
Tolerable upper intake levels (ULs) for vitamin B6 the adult UL is set at 100 mg/day.
Adverse effects have been documented from vitamin B6 dietary supplements, but never from food sources.
Though it is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the dietary upper limit over long periods cause painful and ultimately irreversible neurological problems:
pain and numbness of the extremities.
In severe cases, motor neuropathy may occur, causing difficulty in walking.
Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day, but adverse effects can occur with much less, so intakes over 200 mg/day are not considered safe.
Bacteria residing in the large intestine are known to synthesize B-vitamins, including B6.
The amounts of B6 are not sufficient to meet host requirements, because the vitamins are competitively taken up by non-synthesizing bacteria.
Vitamin B6 is found in a wide variety of foods. In general, meat, fish and fowl are good sources.
Dairy foods and eggs are not.
Crustaceans and mollusks contain about 0.1 mg/100 grams.
Fruit (apples, oranges, pears) contain less than 0.1 mg/100g.
Bioavailability from a mixed diet containing animal- and plant-sourced foods is estimated at being 75%: igher for PLP from meat, fish and fowl, lower from plants.
However, a vegetarian diet does not pose a risk for vitamin B6 deficiency.
Cooking, food storage, and processing losses vary, and in some foods may be more than 50%.
Plant foods lose less during processing, as they contain pyridoxine, which is more stable than the pyridoxal or pyridoxamine forms found in animal-sourced foods.
Milk can lose 30–70% of its vitamin B6 content when dried.
The vitamin is found in the germ, so there is more in whole wheat bread compared to white bread wheat, and more in brown rice compared to white rice.
Amount
(mg per 100 grams)
Whey protein concentrate 1.2
Beef liver, pan-fried 1.0
Tuna, skipjack, cooked 1.0
Beef steak, grilled 0.9
Salmon, Atlantic, cooked 0.9
Chicken breast, grilled 0.7
Pork chop, cooked 0.6
Turkey, ground, cooked 0.6
Banana 0.4
Mushroom, Shiitake, raw 0.3
Potato, baked, with skin 0.3
Sweet potato baked 0.3
Bell pepper, red 0.3
Peanuts 0.3
Avocado 0.25
Spinach 0.2
Chickpeas 0.1
Tofu, firm 0.1
Corn grits 0.1
Milk, whole 0.1 (one cup)
Yogurt 0.1 (one cup)
Almonds 0.1
Bread, whole wheat/white 0.2/0.1
Rice, cooked, brown/white 0.15/0.02
Beans, baked 0.1
Beans, green 0.1
Chicken egg 0.1
In the US, multi-vitamin/mineral products typically contain 2 to 4 mg of vitamin B6 per daily serving as pyridoxine hydrochloride, but a few contain more than 25 mg.
The US National Academy of Medicine sets an adult safety UL at 100 mg/day, and the European Food Safety Authority sets its UL at 25 mg/day.
Vitamin B6 is a nutrient that helps produce energy from protein and helps maintain healthy skin and mucous membranes.
The vitamin provides for normal homocysteine metabolism, normal energy-yielding metabolism, normal psychological function, reduced tiredness and fatigue, and provides for normal cysteine synthesis.
Vitamin B6 is absorbed in the jejunum by passive diffusion.
Most of the vitamin is taken up by the liver, and , the dephosphorylated vitamins are converted to the phosphorylated PLP.
The PLP-albumin complex is released by the liver to circulate in plasma.
Protein-binding capacity limits vitamin storage.
Total body stores, the majority of which is in muscle, with a lesser amount in liver, have been estimated to be in the range of 61 to 167 mg.
Inverse association between intake and risk of future coronary artery disease, and between circulating levels of vitamin B6 concentration and risk of cardiovascular disease.