Recent nutritional studies have indicated prevalent marginal deficiency of vitamin B6 in many segments of the American population. While the consequences of long-term marginal status are unclear, vitamin B6 nutriture is known to affect the efficiency of many physiological processes and host defense mechanisms. Because of a lack of knowledge of the bioavailability of vitamin B6, the adequacy of human diets in meeting the nutritional requirement often cannot be determined. Recent studies indicate that the proportion of pyridoxine beta- glucoside (PN-G) may be a major determinant of the bioavailability of dietary vitamin B6. This research will involve further characterization of the nutritional properties of PN-G, which comprises a major portion of the vitamin B6 of plant-derived foods. The following objectives will be addressed: (1) Whether the utilization of labelled PN-G is influenced by adaptation to the level of chronic PN-G ingestion in the rat and in human subjects; (2) Whether PN- G ingested simultaneously with labelled pyridoxine (PN) may inhibit the metabolic utilization of PN in the rat, in human subjects, and in vitro with key enzymes in vitamin B6 metabolism and function; (3) The nutritional properties of three naturally occurring derivatives of PN-G will also be determined, relative to PN and PN-G, in a rat bioassay with long-term (3-week) administration of the tested compounds. All studies with human subjects will be conducted with deuterium-labelled (d2 and/or d5) forms of the vitamin to permit specific evaluation of metabolism and excretion without concerns of radioisotopic methods. The urinary excretion of deuterated or radiolabelled forms of 4- pyridoxic acid will be a major criterion of the utilization of the ingested labelled compound(s) in vitamin B6 metabolism in in vivo studies. The results of these studies will permit a more accurate evaluation of vitamin B6 nutrition by providing detailed information concerning the nutritional activity of derivatives of PN-glucoside, as well potential variation in the extent of metabolic utilization of PN-glucoside, and its potential inhibitory effect on the metabolism of non-glycosylated vitamin B6.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037481-04
Application #
3236414
Study Section
Nutrition Study Section (NTN)
Project Start
1986-08-01
Project End
1991-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Earth Sciences/Resources
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Quinlivan, Eoin P; Gregory 3rd, Jesse F (2008) DNA digestion to deoxyribonucleoside: a simplified one-step procedure. Anal Biochem 373:383-5
Quinlivan, Eoin P; Gregory 3rd, Jesse F (2007) Reassessing folic acid consumption patterns in the United States (1999 2004): potential effect on neural tube defects and overexposure to folate. Am J Clin Nutr 86:1773-9
Lima, Carolina P; Davis, Steven R; Mackey, Amy D et al. (2006) Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets. J Nutr 136:2141-7
Scheer, Jennifer B; Mackey, Amy D; Gregory 3rd, Jesse F (2005) Activities of hepatic cytosolic and mitochondrial forms of serine hydroxymethyltransferase and hepatic glycine concentration are affected by vitamin B-6 intake in rats. J Nutr 135:233-8
Tseung, Chi-Wah; McMahon, Laura G; Vazquez, Jorge et al. (2004) Partial amino acid sequence and mRNA analysis of cytosolic pyridoxine-beta-D-glucoside hydrolase from porcine intestinal mucosa: proposed derivation from the lactase-phlorizin hydrolase gene. Biochem J 380:211-8
Mackey, Amy D; McMahon, Robert J; Townsend, Justin H et al. (2004) Uptake, hydrolysis, and metabolism of pyridoxine-5'-beta-D-glucoside in Caco-2 cells. J Nutr 134:842-6
Mackey, Amy D; Lieu, Siam O; Carman, Catherine et al. (2003) Hydrolytic activity toward pyridoxine-5'-beta-D-glucoside in rat intestinal mucosa is not increased by vitamin B-6 deficiency: effect of basal diet composition and pyridoxine intake. J Nutr 133:1362-7
Mackey, Amy D; Henderson, George N; Gregory 3rd, Jesse F (2002) Enzymatic hydrolysis of pyridoxine-5'-beta-D-glucoside is catalyzed by intestinal lactase-phlorizin hydrolase. J Biol Chem 277:26858-64
Armada, Linda J; Mackey, Amy D; Gregory 3rd, Jesse F (2002) Intestinal brush border membrane catalyzes hydrolysis of pyridoxine-5'-beta-D-glucoside and exhibits parallel developmental changes of hydrolytic activities toward pyridoxine-5'-beta-D-glucoside and lactose in rats. J Nutr 132:2695-9
Gregory 3rd, J F (1998) Nutritional Properties and significance of vitamin glycosides. Annu Rev Nutr 18:277-96

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