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| | From:  taka00381 (Original Message) | Sent: 10/29/2008 2:08 AM |
It seems that VitB6 is not only essential for the Mead acid synthesis but it also inhibits the major age-related reaction in the body - the Maillard reaction:
Ann N Y Acad Sci. 2005 Jun;1043:807-16.
Pyridoxamine: the many virtues of a maillard reaction inhibitor.
Voziyan PA, Hudson BG.
Division of Nephrology, Vanderbilt University Medical Center, S-3223 MCN, 1161 21st Avenue South, Nashville, TN 37232-2372, USA.
Pyridoxamine (PM) is one of three natural forms of vitamin B6. It is a critical transient intermediate in catalysis of transamination reactions by vitamin B6-dependent enzymes. The discovery eight years ago that PM can inhibit the Maillard reaction stimulated new interest in this B6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. PM application in diabetic nephropathy has now progressed to a phase III clinical trial. Investigation of the PM mechanism of action demonstrated that PM inhibits post-Amadori steps of the Maillard reaction by sequestering catalytic metal ions and blocking oxidative degradation of Amadori intermediate. PM also has the capacity to scavenge toxic carbonyl products of sugar and lipid degradation, and to inhibit reactive oxygen species. These multiple activities position PM as a promising drug candidate for treatment of multifactorial chronic conditions in which oxidative reactions and/or carbonyl compounds confer pathogenicity.
PMID: 16037308
J Biol Chem. 2003 Oct 24;278(43):42012-9. Epub 2003 Aug 15.
Pyridoxamine traps intermediates in lipid peroxidation reactions in vivo: evidence on the role of lipids in chemical modification of protein and development of diabetic complications.
Metz TO, Alderson NL, Chachich ME, Thorpe SR, Baynes JW.
Department of Chemistry and Biochemistry, University of South Carolina, Graduate Science Research Center, 631 Sumter Street, Columbia, SC 29208, USA.
Maillard or browning reactions between reducing sugars and protein lead to formation of advanced glycation end products (AGEs) and are thought to contribute to the pathogenesis of diabetic complications. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) inhibit both the formation of AGEs and development of complications in animal models of diabetes. PM also inhibits the chemical modification of protein by advanced lipoxidation end products (ALEs) during lipid peroxidation reactions in vitro. We show here that several PM adducts, formed in incubations of PM with linoleate and arachidonate in vitro, are also excreted in the urine of PM-treated animals. The PM adducts N-nonanedioyl-PM (derived from linoleate), N-pentanedioyl-PM, N-pyrrolo-PM, and N-(2-formyl)-pyrrolo-PM (derived from arachidonate), and N-formyl-PM and N-hexanoyl-PM (derived from both fatty acids) were quantified by liquid chromatography-mass spectrometry analysis of rat urine. Levels of these adducts were increased 5-10-fold in the urine of PM-treated diabetic and hyperlipidemic rats, compared with control animals. We conclude that the PM functions, at least in part, by trapping intermediates in AGE/ALE formation and propose a mechanism for PM inhibition of AGE/ALE formation involving cleavage of alpha-dicarbonyl intermediates in glycoxidation and lipoxidation reactions. We also conclude that ALEs derived from polyunsaturated fatty acids are increased in diabetes and hyperlipidemia and may contribute to development of long term renal and vascular pathology in these diseases.
PMID: 12923193
J Biol Chem. 2000 Jul 14;275(28):21177-84.
Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine.
Onorato JM, Jenkins AJ, Thorpe SR, Baynes JW.
Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208, USA.
Maillard or browning reactions lead to formation of advanced glycation end products (AGEs) on protein and contribute to the increase in chemical modification of proteins during aging and in diabetes. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) have proven effective in animal model and clinical studies as inhibitors of AGE formation and development of diabetic complications. We report here that PM also inhibits the chemical modification of proteins during lipid peroxidation (lipoxidation) reactions in vitro, and we show that it traps reactive intermediates formed during lipid peroxidation. In reactions of arachidonate with the model protein RNase, PM prevented modification of lysine residues and formation of the advanced lipoxidation end products (ALEs) N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, malondialdehyde-lysine, and 4-hydroxynonenal-lysine. PM also inhibited lysine modification and formation of ALEs during copper-catalyzed oxidation of low density lipoprotein. Hexanoic acid amide and nonanedioic acid monoamide derivatives of PM were identified as major products formed during oxidation of linoleic acid in the presence of PM. We propose a mechanism for formation of these products from the 9- and 13-oxo-decadienoic acid intermediates formed during peroxidation of linoleic acid. PM, as a potent inhibitor of both AGE and ALE formation, may prove useful for limiting the increased chemical modification of tissue proteins and associated pathology in aging and chronic diseases, including both diabetes and atherosclerosis.
PMID: 10801874
Cell Mol Life Sci. 2005 Aug;62(15):1671-81.
Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage.
Voziyan PA, Hudson BG.
Division of Nephrology, Vanderbilt University Medical Center, S-3223 MCN, 1161 21st Avenue South, Nashville, Tennessee 37232-2372, USA.
The discovery that pyridoxamine (PM) can inhibit glycation reactions and the formation of advanced glycation end products (AGEs) stimulated new interest in this B6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. The mechanism of action of PM includes: (i) inhibition of AGE formation by blocking oxidative degradation of the Amadori intermediate of the Maillard reaction; (ii) scavenging of toxic carbonyl products of glucose and lipid degradation; and (iii) trapping of reactive oxygen species. The combination of these multiple activities along with PM safety posture it as a promising drug candidate for treatment of diabetic complications as well as other multifactorial chronic conditions in which oxidative reactions and carbonyl compounds confer pathogenicity.
PMID: 15905958 |
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Another face of VitB6 is that it inhibits prolactin secretion. Prolactin is a pituitary immunity stimulating hormone normally secreted during sleep or lactation but often overproduced in chronic inflammatory diseases and allergies.
Endocrinology. 2006 Aug;147(8):3936-42. Epub 2006 May 11.
Pyridoxal phosphate inhibits pituitary cell proliferation and hormone secretion.
Ren SG, Melmed S.
Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, California 90048, USA.
Pyridoxal phosphate (PLP), a bioactive form of pyridoxine, dose-dependently (10-1000 microm) inhibited cell proliferation in rat pituitary MMQ and GH3 cells and in mouse AtT-20 cells. After 4 d, MMQ cell numbers were reduced by up to 81%, GH3 cell numbers were reduced by up to 64% (P < 0.05), and AtT-20 cell numbers were reduced by up to 90%. Cell proliferation rates recovered and dose-dependently reverted to control levels after PLP withdrawal. After 4 d, PLP (400 and 1000 microm) decreased [3H]thymidine incorporation by up to 71% (P < 0.05). PLP (400-1000 microm) reduced GH3 cell GH and prolactin secretion and AtT-20 cell ACTH secretion (adjusted for cell number) by approximately 70% after 2 d. The 100 microm PLP also inhibited prolactin secretion (65%, P < 0.05) in primary rat pituitary cells treated for 2 d. PLP decreased the percentage of AtT-20 and GH3 cells in S phase and increased those in G0-G1 phase. Furthermore, PLP induced AtT-20 and GH3 cell apoptosis (28 vs. 6, P < 0.05; 26 vs. 3, P < 0.05, respectively) and dose-dependently reduced content of the antiapoptosis gene Bcl-2. These results indicate that pharmacological doses of PLP inhibit pituitary cell proliferation and hormone secretion, in part mediated through PLP-induced cell-cycle arrest and apoptosis. Pyridoxine may therefore be appropriate for testing as a relatively safe drug for adjuvant treatment of hormone-secreting pituitary adenomas.
PMID: 16690808
Boll Soc Ital Biol Sper. 1984 Feb 28;60(2):273-8.
[Influence of administration of pyridoxine on circadian rhythm of plasma ACTH, cortisol prolactin and somatotropin in normal subjects]
Barletta C, Sellini M, Bartoli A, Bigi C, Buzzetti R, Giovannini C.
The influence of vitamin B6 in a dosage of 300 mg X 2 in 24 hrs, on circadian rhythm of plasmatic ACTH, cortisol, prolactin and somatotropin have been studied in 10 normal women. After vitamin B6 24 hrs pattern of ACTH and cortisol is unchanged; prolactin levels are slightly lower, in a statistically unsignificant proportion the night peak of growth hormone is higher in a statistically significant proportion (p. 0.05). The effect of vitamin B6 is likely to me mediated by dopaminergic receptors at hypothalamic level as previous studies by other Authors appear to prove.
PMID: 6324828
N Engl J Med. 1982 Aug 12;307(7):444-5.
Pyridoxine (B6) suppresses the rise in prolactin and increases the rise in growth hormone induced by exercise.
Moretti C, Fabbri A, Gnessi L, Bonifacio V, Fraioli F, Isidori A.
PMID: 7088124
Horm Metab Res. 1985 Jan;17(1):46-7.
Pyridoxine (Vit. B6) decreases opioids-induced hyperprolactinemia.
Vescovi PP, Gerra G, Rastelli G, Ceresini G, Moccia G.
PMID: 3967846
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