Vitamin B6 is a water-soluble
vitamin and is part of the
vitamin B complex group.
Pyridoxal phosphate (PLP) is the active
form and is a
cofactor in
many reactions of
amino acid metabolism,
including transamination, deamination, and decarboxylation. PLP
also is necessary for the enzymatic reaction governing the release
of
glucose from
glycogen.
History
Vitamin B
6 is a water-soluble compound that was
discovered in the 1930s during nutrition studies on rats. In 1934,
a Hungarian physician, Paul Gyorgy discovered a substance that was
able to cure a skin disease in rats (dermititis acrodynia), this
substance he named vitamin B6. In 1938, Lepkovsky isolated vitamin
B6 from rice bran. Harris and Folkers in 1939 determined the
structure of pyridoxine, and, in 1945, Snell was able to show that
there are two forms of vitamin B6, pyridoxal and pyridoxamine.
Vitamin B6 was named pyridoxine to indicate its structural homology
to
pyridine. All three forms of vitamin
B
6 are precursors of an activated compound known as
pyridoxal 5'-phosphate (PLP),
which plays a vital role as the cofactor of a large number of
essential enzymes in the human body.
Enzymes dependent on PLP focus a wide variety of chemical reactions
mainly involving amino acids. The reactions carried out by the
PLP-dependent enzymes that act on amino acids include transfer of
the amino group, decarboxylation, racemization, and beta- or
gamma-elimination or replacement. Such versatility arises from the
ability of PLP to covalently bind the substrate, and then to act as
an electrophilic catalyst, thereby stabilizing different types of
carbanionic reaction intermediates.
Overall, the Enzyme Commission (EC;
http://www.chem.qmul.ac.uk/iubmb/enzyme/ ) has catalogued more than
140 PLP-dependent activities, corresponding to ~4% of all
classified activities.
The effectiveness as treatment for
PMS,
PMDD, and
clinical
depression is debatable. B6 is also considered an experimental
but potentially effective treatment for
schizophrenia and
autism.
Forms
Seven forms of this vitamin are known:
All forms except PA can be interconverted.
Functions
Pyridoxal phosphate, the metabolically active form of vitamin
B
6, is involved in many aspects of
macronutrient metabolism,
neurotransmitter synthesis,
histamine synthesis,
hemoglobin synthesis and function and
gene expression. Pyridoxal phosphate
generally serves as a coenzyme for many reactions and can help
facilitate decarboxylation, transamination, racemization,
elimination, replacement and beta-group interconversion reactions.
The liver is the site for vitamin B6 metabolism.
Amino acid metabolism
Pyridoxal phosphate (PLP) is a cofactor in transaminases that can
catabolize amino acids. PLP is also an essential component of two
enzymes that converts
methionine to
cysteine via two reactions. Low vitamin
B
6 status will result in decreased activity of these
enzymes. PLP is also an essential cofactor for enzymes involved in
the metabolism of
selenomethionine
to
selenohomocysteine and then
from selenohomocysteine to
hydrogen
selenide. Vitamin B
6 is also required for the
conversion of
tryptophan to
niacin and low vitamin B
6 status will
impair this conversion. PLP is also used to create physiologically
active amines by decarboxylation of amino acids. Some notable
examples of this include:
histidine to
histamine,
tryptophan to
serotonin,
glutamate to
GABA
(
gamma-aminobutyric acid),
and
dihydroxyphenylalanine to
dopamine.
Gluconeogenesis
Vitamin B
6 also plays a role in
gluconeogenesis. Pyridoxal phosphate can
catalyze transamination reactions that are essential for the
providing amino acids as a substrate for gluconeogenesis. Also,
vitamin B
6 is a required coenzyme of glycogen
phosphorylase, the enzyme that is necessary for glycogenolysis to
occur.
Lipid metabolism
Vitamin B
6 is an essential component of enzymes that
facilitate the biosynthesis of
sphingolipids. Particularly, the synthesis of
ceramide requires PLP. In this reaction
serine is decarboxylated and combined with palmitoyl-CoA to form
sphinganine which is combined with a fatty acyl CoA to form
dihydroceramide. Dihydroceramide is then further desaturated to
form ceramide. In addition, the breakdown of sphingolipids is also
dependent on vitamin B
6 since S1P Lyase, the enzyme
responsible for breaking down sphingosine-1-phosphate, is also PLP
dependent.
Metabolic functions
The primary role of vitamin B
6 is to act as a coenzyme
to many other enzymes in the body that are involved predominantly
in metabolism. This role is performed by the active form, pyridoxal
phosphate. This active form is converted from the two other natural
forms founds in food: pyridoxal, pyridoxine and pyridoxamine.
Vitamin B
6 is involved in the following metabolic
processes:
- amino acid, glucose and lipid metabolism
- neurotransmitter synthesis
- histamine synthesis
- hemoglobin synthesis and function
- gene expression
Amino acid metabolism
Pyridoxal phosphate is involved in almost all amino acid
metabolism, from synthesis to breakdown.
1. Transamination: transaminase enzymes needed to break down amino
acids are dependent on the presence of pyridoxal phosphate. The
proper activity of these enzymes are crucial for the process of
moving amine groups from one amino acid to another.
2. Transsulfuration: Pyridoxal phosphate is a coenzyme needed for
the proper function of the enzymes cystathionine synthase and
cystathionase. These enzymes work to transform methionine into
cysteine.
3. Selenoamino acid metabolism: Selenomethionine is the primary
dietary form of selenium. Pyridoxal phosphate is needed as a
cofactor for the enzymes that allow selenium to be used from the
dietary form. Pyridoxal phosphate also plays a cofactor role in
releasing selenium from selenohomocysteine to produce hydrogen
selenide. This hydrogen selenide can then be used to incorporate
selenium into selenoproteins.
4. Vitamin B
6 is also required for the conversion of
tryptophan to niacin and low vitamin B
6 status will
impair this conversion.
Gluconeogenesis
Vitamin B
6 also plays a role in gluconeogenesis.
Pyridoxal phosphate can catalyze transamination reactions that are
essential for providing amino acids as a substrate for
gluconeogenesis. Also, vitamin B
6 is a required coenzyme
of glycogen phosphorylase, the enzyme that is necessary for
glycogenolysis to occur.
Neurotransmitter synthesis
Pyridoxal phosphate-dependent enzymes play a role in the
biosynthesis of four important
neurotransmitters:
serotonin,
epinephrine,
norepinephrine and
gamma-aminobutyric acid. Serine
racemase, which synthesizes the neuromodulator D-serine, is also a
pyridoxal phosphate-dependent enzyme.
Histamine synthesis
Pyridoxal phosphate is involved in the metabolism of
histamine.
Hemoglobin synthesis and function
Pyridoxal phosphate aids in the synthesis of heme and can also bind
to two sites on hemoglobin to enhance the oxygen binding of
hemoglobin.
Gene expression
It transforms homocysteine in then cistation then in cysteine,
leading indirectly to
epigenetics
phenomena of nature is still not certain; for this reason,
Pyridoxal phosphate should be used in the next experiments about
epigenetics. Pyridoxal phosphate has
been implicated in increasing or decreasing the expression of
certain genes. Increased intracellular levels of the vitamin will
lead to a decrease in the transcription of glucocorticoid hormones.
Also, vitamin B
6 deficiency will lead to the increased
expression of albumin mRNA. Also, pyridoxal phosphate will
influence gene expression of glycoprotein IIb by interacting with
various transcription factors. The result is inhibition of platelet
aggregation.
Dietary reference intakes
Life Stage Group |
RDA/AI* |
UL |
Infants
0–6 months
7–12 months
|
(mg/day)
0.1*
0.3* |
(mg/day)
ND
ND |
Children
1-3 yrs
4-8 yrs |
0.5
0.6 |
30
40 |
Males
9-13 yrs
14-18 yrs
19-50 yrs
50- >70 yrs |
1.0
1.3
1.3
1.7 |
60
80
100
100 |
Females
9-13 yrs
13-18 yrs
19-50 yrs
50- >70 yrs |
1.0
1.2
1.3
1.5 |
60
80
100
100 |
Pregnancy
<18 yrs
</18>19-50 yrs |
1.9
1.9 |
80
100 |
Lactation
<18 yrs
</18>19-50 yrs |
2.0
2.0 |
80
100 |
The Institute of Medicine notes that "No adverse effects associated
with Vitamin B
6 from food have been reported. This does
not mean that there is no potential for adverse effects resulting
from high intakes. Because data on the adverse effects of Vitamin
B
6 are limited, caution may be warranted. Sensory
neuropathy has occurred from high intakes of supplemental forms."
See the full
Dietary Reference Intake table from the
Institute of Medicine's.
Food sources
Vitamin B
6 is widely distributed in foods in both its
free and bound forms. Good sources include meats, whole grain
products, vegetables, and nuts. Cooking, storage and processing
losses of vitamin B
6 vary and in some foods may be more
than 50%,McCormick, D. B. Vitamin B
6 In: Present
Knowledge in Nutrition (Bowman, B. A. and Russell, R. M., eds), 9th
edition, vol. 2, p.270. Washington, D.C.: International Life
Sciences Institute, 2006. depending on the form of vitamin present
in the food. Plant foods lose the least during processing as they
contain mostly pyridoxine which is far more stable than the
pyridoxal or pyridoxamine found in animal foods. For example, milk
can lose 30-70% of its vitamin B
6 content when dried.
Vitamin B6 is found in the germ and aleurone layer of grains and
milling results to the reduction of this vitamin in white flour.
Freezing and canning are other food processing methods that results
in the loss of vitamin B6 in foods.
Absorption
Vitamin B
6 is absorbed in the
jejunum and ileum via passive diffusion. With the
capacity for absorption being so great, animals are able to absorb
quantities much greater than what is needed for physiological
demands. The absorption of pyridoxal phosphate and pyridoxamine
phosphate involves their dephosphorylation catalyzed by a
membrane-bound alkaline phosphatase. Those products and
non-phosphorylated vitamers in the digestive tract are absorbed by
diffusion, which is driven by trapping of the vitamin as
5'-phosphates through the action of phosphorylation (by a pyridoxal
kinase) in the jejunal mucosa. The trapped pyridoxine and
pyridoxamine are oxidized to pyridoxal phosphate in the
tissue.
Excretion
The products of vitamin B
6 metabolism are excreted in
the urine; the major product of which is 4-pyridoxic acid. It has
been estimated that 40-60% of ingested vitamin B
6 is
oxidized to 4-pyridoxic acid. Several studies have shown that
4-pyridoxic acid is undetectable in the urine of vitamin
B
6 deficient subjects, making it a useful clinical
marker to assess the vitamin B
6 status of an individual.
Other products of vitamin B
6metabolism that are excreted
in the urine when high doses of the vitamin have been given include
pyridoxal, pyridoxamine, and pyridoxine and their phosphates. A
small amount of vitamin B6 is also excreted in the feces.
Deficiencies
The classic clinical syndrome for
B6 deficiency is a
seborrhoeic dermatitis-like eruption,
atrophic glossitis with
ulceration,
angular
cheilitis,
conjunctivitis,
intertrigo, and neurologic symptoms of
somnolence, confusion, and
neuropathy.
While severe vitamin B
6 deficiency results in
dermatologic and neurologic changes, less severe cases present with
metabolic lesions associated with insufficient activities of the
coenzyme pyridoxal phosphate. The most prominent
of the lesions is due to impaired
tryptophan-
niacin
conversion. This can be detected based on urinary excretion of
xanthurenic acid after an oral
tryptophan load. Vitamin B
6 deficiency can also result
from impaired
transsulfuration of
methionine to
cysteine. The pyridoxal phosphate-dependent
transaminases and
glycogen phosphorylase provide the
vitamin with its role in
gluconeogenesis, so deprivation of vitamin
B
6 results in impaired glucose tolerance.
A deficiency of vitamin B
6 alone is relatively uncommon
and often occurs in association with other vitamins of the B
complex. The elderly and alcoholics have an increased risk of
vitamin B
6 deficiency, as well as other micronutrient
deficiencies. Renal patients undergoing dialysis may experience
vitamin B6 deficiency. The availability of vitamin B6 to the body
can be affected by certain drugs such as anticonvulsants and
corticosteriods.
Clinical assessment of vitamin B6
Pyridoxal phosphate in the plasma is considered to be one of the
best indicator of vitamin B6 status in the body. When plasma
pyridoxal phosphate is less than 10nmol/L, it is indicative of
vitamin B6 deficiency. Urinary 4-pyridoxic acid is also an
indicator of vitamin B6 deficiency. Urinary 4-pyridoxic of less
than 3.0 mmol/day is suggestive of vitamin B6
deficiency.
Toxicity
An overdose of pyridoxine can cause a temporary deadening of
certain nerves such as the proprioceptory nerves; causing a feeling
of disembodiment common with the loss of
proprioception. This condition is reversible
when supplementation is stopped.
Vitamin and Mineral Supplement Fact Sheets Vitamin
B6
Because adverse effects have only been documented from vitamin
B
6 supplements and never from food sources, this article
only discusses the safety of the supplemental form of vitamin
B
6 (pyridoxine). Although vitamin B
6 is a
water-soluble vitamin and is excreted in the urine, very high doses
of pyridoxine over long periods of time may result in painful
neurological symptoms known as sensory
neuropathy. Symptoms include pain and numbness of
the extremities, and in severe cases difficulty walking. Sensory
neuropathy typically develops at doses of pyridoxine in excess of
1,000 mg per day. However, there have been a few case reports
of individuals who developed sensory neuropathies at doses of less
than 500 mg daily over a period of months. None of the
studies, in which an objective neurological examination was
performed, found evidence of sensory nerve damage at intakes of
pyridoxine below 200 mg/day. In order to prevent sensory
neuropathy in virtually all individuals, the Food and Nutrition
Board of the Institute of Medicine set the tolerable upper intake
level (UL) for pyridoxine at 100 mg/day for adults. Because
placebo-controlled studies have generally failed to show
therapeutic benefits of high doses of pyridoxine, there is little
reason to exceed the UL of 100 mg/day.
Preventive roles and therapeutic uses
At least one preliminary study has found that this vitamin may
increase
dream vividness or the ability to
recall dreams. It is thought that this effect may be due to the
role this vitamin plays in the conversion of
tryptophan to
serotonin.
The intake of vitamin B, from either diet or supplements, could cut
the risk of
Parkinson’s
disease by half according to a prospective study from the
Netherlands. "Stratified analyses showed that this association was
restricted to smokers," wrote the authors.
Pyridoxine has a role in preventing heart disease. Without enough
pyridoxine, a compound called homocysteine builds up in the body.
Homocysteine damages blood vessel linings, setting the stage for
plaque buildup when the body tries to heal the damage.Vitamin B6
prevents this buildup, thereby reducing the risk of heart attack.
Pyridoxine lowers blood pressure and blood cholesterol levels and
keeps blood platelets from sticking together. All of these
properties work to keep heart disease at bay.
Nutritional supplementation with high dose vitamin B
6
and
magnesium is one of the most popular
alternative medicine choices
for
autism.
Some studies suggest that the B6-magnesium combination can also
help
attention deficit
disorder, citing improvements in hyperactivity,
hyperemotivity/aggressiveness and improved school attention.
A lack of the vitamin may play a role in sensitivity to monosodium
glutamate (MSG), a flavor enhancer. This sensitivity can cause
headaches, pain and tingling of the upper extremities, nausea, and
vomiting. In both of these syndromes, supplementation of pyridoxine
alleviates symptoms only when people were deficient in the vitamin
to begin with.
If people are marginally deficient in vitamin B6, they may be more
susceptible to carpal tunnel syndrome. Carpal tunnel syndrome is
characterized by pain and tingling in the wrists after performing
repetitive movements or otherwise straining the wrist on a regular
basis. Vitamin B6 has been shown in at least two small-scale
clinical studies to have a beneficial effect on carpal tunnel
syndrome, particularly in cases where no trauma or overuse etiology
for the CTS is known.
Vitamin B6 has long been publicized as a cure for premenstrual
syndrome (PMS). Study results conflict as to which symptoms are
eased, but most of the studies confirm that women who take B6
supplements have reductions in bloating, breast pain, and
premenstrual acne flare, a condition in which pimples break out
about a week before a woman's period begins.There is strong
evidence that pyridoxine supplementation, starting ten days before
the menstrual period, prevents most pimples from forming. This
effect is due to the vitamin's role in hormone and prostaglandin
regulation. Skin blemishes are typically caused by a hormone
imbalance, which vitamin B6 helps to regulate.
Mental depression is another condition which may result from low
vitamin B6 intake. Because of pyridoxine's role in serotonin and
other neurotransmitter production, supplementation often helps
depressed people feel better, and their mood improves
significantly. It may also help improve memory in older
adults.
It is also suggested that ingestion of vitamin B6 can alleviate
some of the many symptoms of an alcoholic
hangover and
morning
sickness from pregnancy. This might be due to B6's mild
diuretic effect. Though the mechanism is
not known, results show that pyridoxamine has a therapeutic effects
in clinical trials for diabetic nephropathy.
References
External links