Join Date: Aug 2006
Location: Great Lakes
This post is going to expand the P5P concept:
Today I am searching for more pyridoxal kinase problems. When I was first on the net 10 yrs + ago the data on pyridoxal kinase was just being released in some nutrition journals. Today there is much more available.
Here is an interesting 2007 paper that found that certain things in Gingko
block the actions of pyridoxal kinase:
FEBS J. 2007 Feb;274(4):1036-45. Epub 2007 Jan 19.Click here to read Links
The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba.
Kästner U, Hallmen C, Wiese M, Leistner E, Drewke C.
Institut für Pharmazeutische Biologie, Universität Bonn, Germany.
Ginkgotoxin (4'-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B(6). Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B(6) antivitamins including ginkgotoxin on recombinant homogeneous human pyridoxal kinase (EC 220.127.116.11). It is shown that ginkgotoxin serves as an alternate substrate for this enzyme with a lower K(m) value than pyridoxal, pyridoxamine or pyridoxine. Thus, the presence of ginkgotoxin leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly also in vivo. Our observations are discussed in light of Ginkgo medications used as nootropics.
PMID: 17250738 [PubMed - indexed for MEDLINE]
And here is a paper on racial differences in red blood cells and pyridoxal kinase:
Haematologica. 2006 Jun;91(6):801-4. Epub 2006 May 16.Click here to read Links
The genetic basis of human erythrocyte pyridoxal kinase activity variation.
Flanagan JM, Beutler E.
Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thirty years ago we reported that erythrocyte pyridoxal kinase activity of African-Americans was strikingly lower than that of persons with European ancestry in a tissue-specific manner. At the time, it was impossible to elucidate the mechanism by which evolution had selectively lowered the enzyme activity in one cell type but not in others. We have now identified a promoter mutation with potential erythroid-specific properties that could be the basis of a novel mechanism of controlling cell-specific decreased activity of an essential enzyme.
PMID: 16704963 [PubMed - indexed for MEDLINE]
I don't have access however to the whole paper, to understand the meaning of it.
This paper is from 1997...and mentions alcohol:
Eur J Clin Nutr. 1997 Nov;51 Suppl 3:S39-45.Links
Dietary and other determinants of vitamin B6 parameters.
Brussaard JH, Löwik MR, van den Berg H, Brants HA, Bemelmans W.
TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
OBJECTIVE: To assess the dietary, physical, biochemical and lifestyle determinants of vitamin B6 status parameters among healthy adults. DESIGN AND SUBJECTS: Dietary intake and status variables as well as other relevant characteristics were determined among 444 adults, aged 20-79 y and stratified for sex and 10-years age classes with a randomly selected control group (n = 300) and an over representation of persons with a low habitual vitamin B6 intake (n = 144). RESULTS AND CONCLUSIONS: The direct status parameters (plasma pyridoxal-5'-phosphate (PLP), plasma pyridoxal + PLP (PL + PLP), and 4-pyridoxic acid (4-PA) excretion) were clearly related to dietary variables and plasma concentrations of vitamin C (women only), vitamin B12 and folate. The total percentage of variance in p-PLP explained in multivariate regression analysis was 41 and 30% in men and women, respectively. The most important explaining variables besides vitamin B6 intakes were variables closely related to PLP-metabolism: albumin and alkaline phosphatase. Biochemical function related status parameters showed less statistically significant correlations with dietary variables. Four to 24% of the variance in the stimulation coefficients of erythrocyte aspartate aminotransferase (alpha-EAST) and erythrocyte alanine aminotransferase (alpha-EALT) and change in homocysteine excretion after a methionin load was explained by a combination of dietary, physiological and lifestyle related variables. The low percentages explained for some variables, notably alpha-EAST (women) and the change in homocysteine excretion after a methionin load (men), suggests that these parameters are not sensitive to the level of vitamin B6 intake as found in the present study. Alcohol contributed in many of the explaining models for vitamin B6 status parameters. Therefore, when assessing the vitamin B6 status of a population, it is important to estimate the level of alcohol intake as well. Furthermore, the results illustrate the importance of sex related differences in the metabolism of some parameters, especially homocysteine excretion. The variance in the clinical function related status parameter measured in the present study, handgripstrength, was explained for 50% by a combination of age, body weight and Quetelet Index (QI) with no important contribution of dietary variables.
PMID: 9598767 [PubMed - indexed for MEDLINE]
This is another version of that paper...
1: Eur J Clin Nutr. 1997 Nov;51 Suppl 3:S32-8.Links
Micronutrient status, with special reference to vitamin B6.
Brussaard JH, Löwik MR, van den Berg H, Brants HA, Kistemaker C.
TNO Food and Nutrition Research Institute, Zeist, The Netherlands.
OBJECTIVE: To assess the adequacy of micronutrient status among the adult population, with special reference to vitamin B6 status. DESIGN AND SUBJECTS: Micronutrient status was assessed among a random sample of the adult Dutch population (reference group, n = 300), aged 20-79 y, stratified for age and gender, and among a group with a low vitamin B6 intake (n = 144). RESULTS: Low vitamin B6 groups had lower mean levels of erythrocyte and plasma pyridoxal (PL) and pyridoxal-5'-phosphate (PLP), urinary excretion of 4-pyridoxic acid, basal and stimulated erythrocyte aspartate aminotransferase (EAST) and erythrocyte alanine aminotransferase (EALT) activities and EAST stimulation coefficients but not of EALT stimulation coefficients, handgripstrength and 24 h homocysteine excretion before and after a methionin load test. Besides, plasma levels of vitamin C, B12 and folate were lower among low B6 than among reference groups indicating a combined low vitamin status. Direct biomarkers of vitamin B6 intake (plasma PLP and 4-pyridoxic acid excretion) were significantly related to more functional parameters (EAST, EALT and alpha-EAST). Among random reference groups the prevalence of plasma PLP values below 19 nmol/l was 3-7% for different age-gender groups, with the highest value of 16% among men aged 50-79 years. The prevalence of high values of erythrocyte glutathion reductase stimulation coefficient (alpha-EGR) and low levels of serum vitamin B12 and C was not more than 5% among different age-gender reference groups. CONCLUSIONS: Direct biomarkers of vitamin B6 intake confirmed the preselection of a group with a low vitamin B6 intake. The results suggest that the sensitivity of vitamin B6 status parameters for low vitamin B6 intake was highest for the direct vitamin B6 status parameters and lowest for handgripstrength and homocysteine excretion after a methionin load; results for enzyme stimulation coefficients were intermediate. The prevalence of below adequate status parameters for vitamin B2, B6, B12 and C was not more than 7% among the different age-gender groups, with the exception of a value of 16% for plasma PLP levels below 19 nmol/l among men aged 50-79.
PMID: 9598766 [PubMed - indexed for MEDLINE]
Zinc deficiency may impact B6 metabolism:
Nutr Rev. 1990 Jun;48(6):255-8.Links
Zinc and the regulation of vitamin B6 metabolism.
[No authors listed]
Pyridoxal kinase, a key enzyme in the formation of vitamin B6 coenzymes, requires a zinc-ATP complex as a substrate. Recent findings show that zinc-metallothionein facilitates the formation of the zinc-ATP complex. Thus, the concentration of zinc-metallothionein in tissues may serve in the regulation of vitamin B6 metabolism.
PMID: 1365753 [PubMed - indexed for MEDLINE]
This is a huge article and note the date 1982:
Q Rev Drug Metab Drug Interact. 1982;4(4):289-331.Links
Drug-pyridoxal phosphate interactions.
Ebadi M, Gessert CF, Al-Sayegh A.
In this review it has been pointed out that vitamin B6 and its vitamers can be involved in many interactions with a number of drugs, as well as with the actions of various endocrines and neurotransmitters. Nutritional deficiencies, especially of vitamins and proteins, can affect the manner in which drugs undergo biotransformation, and thereby may also modify the therapeutic efficacy of certain drugs. The differences between nutritional vitamin B6 deficiency and the hereditary disorder producing pyridoxine dependency are discussed. In addition to a pyridoxine deficiency being able to adversely affect drug actions, the improper supplementation with vitamin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridoxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions among pyridoxine vitamers, both phosphorylated and non-phosphorylated, are briefly discussed, particularly regarding their pharmacokinetic properties. The ways in which the normal biochemical functions of vitamin B6 may be interfered with by various drugs are reviewed. (1) The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pyridoxine hydrochloride will prevent or stop these seizures. (2) The acute ingestion of excessive monosodium glutamate will, in some individuals, cause a group of symptoms including among others headache, weakness, stiffness, and heartburn, collectively known as the 'Chinese Restaurant Syndrome.' These symptoms can be prevented by prior supplementation with vitamin B6. The beneficial effect is ascribed to the correction of a deficiency in the activity of glutamic oxaloacetic transaminase, an enzyme that is dependent on pyridoxal phosphate. Some interesting relationships are pointed out between vitamin B6, picolinic acid, and zinc. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate; therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phosphate, on the other hand, appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase.(ABSTRACT TRUNCATED AT 400 WORDS)
PIP: This review examines the interaction of pyridoxal phosphate with select neuroendocrine and neuropharmacological systems and their health related therapeutic implications. Vitamin B6 and its vitamers can be involved in many interactions with a number of drugs as well as the actions of various endocrines and neurotransmitters. Nutritional deficiencies, particularly of vitamins and proteins, can affect the manner in which drugs undergo biotransformation and thus may modify the therapeutic efficacy of certain drugs. In addition to pyridoxine deficiency adversely affecting drug actions, improper supplementation with viatmin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridocxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions amony pyridoxine vitamers, both phosphorylated and nonphosphorylated, are briefly discussed, particularly concerning their pharmacokinetic properties. The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pryidoxine hydrochloride prevents or stops these seizures. The acute ingestion of excessive monosodium glutamate will, in some persons, cause a group of symptoms, including headache, weakness, stiffness, and heartburn, collectively known as the "Chinese Restaurant Syndrome." These symptoms can be prevented by prior supplementation with vitamin B6. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate. Therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phospate appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase. Treatment with daily pyridoxine can reverse a state of depression induced in women who take oral contraceptives (OCs). 1 hypothesis to explain this effect is that the OC is somehow causing a deficiency of seroton serotonin in the brain and that the vitamin B6 helps to overcome this deficiency through the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, pyridoxal phosphate in physiological concentrations seems to function as an endogenous "down regulator" of several receptor sites, including estrogen, progesterone, and androgen.
PMID: 6087425 [PubMed - indexed for MEDLINE]
All truths are easy to understand once they are discovered; the point is to discover them.-- Galileo Galilei
This is a fledgling hummingbird resting and drying off after having a bath in my sprinkling hose near his feeder, 2015. He is watching 2 others dashing about in the dripping leaves.
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Last edited by mrsD; 11-11-2007 at 02:53 PM.