title: Effects of zinc deficiency and zinc supplementation on homocysteine levels and related enzyme expression in rats.
abstract: Methionine synthase (MS) and betaine-homocysteine methyltransferase (BHMT) are both zinc (Zn)-dependent methyltransferases and involved in the methylation of homocysteine. The objective of this study was to investigate the effects of dietary Zn supply on homocysteine levels and expression of the two enzymes in growing rats. Male weanling Sprague-Dawley rats were assigned randomly to four dietary groups (n=8/group) for 3 weeks: Zn deficient (ZD; <1mg Zn/kg); Zn control (ZC; 30mg Zn/kg); Zn supplemented (ZS; 300mg Zn/kg); pair fed (PF; 30mg Zn/kg) to the ZD group. Serum and femur Zn concentrations were 83% and 58% lower in ZD, and 49% and 62% higher in ZS compared to ZC (P<0.001), respectively. The ZD rats had lower feed intake (37%), body weight gains (45%), liver (43%) and kidney (31%) weights than those of ZC (P<0.001), but these parameters in ZD were not significantly different from the PF controls. Serum homocysteine concentrations were 65% higher in ZD compared to PF (P<0.05), and there was no significant difference in serum folate levels between ZD and PF groups. The mRNA expression of liver and kidney MS was 57% and 38% lower in ZD than PF (P<0.001), respectively. Hepatic and renal BHMT mRNA levels were not altered in ZD compared to controls. The aforementioned measurements were not significantly different between ZS and ZC groups, except Zn levels. These results demonstrated that homocysteine homeostasis appeared to be disturbed by Zn deficiency but not Zn supplementation, and elevated serum homocysteine might be due to reduced expression of MS during Zn deficiency.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Jing
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Research Centre, Winnipeg, MB R2H 2A6, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Rech
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Richardson College for the Environmental and Science Complex, University of Winnipeg, Winnipeg, MB R3B 2E9, Canada.
authors.forename: Douglas
authors.initials: D
authors.lastname: Goltz
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Research Centre, Winnipeg, MB R2H 2A6, Canada.
authors.forename: Carla G
authors.initials: CG
authors.lastname: Taylor
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada. Electronic address: James.House@umanitoba.ca.
authors.forename: James D
authors.initials: JD
authors.lastname: House
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight; D004032:Diet; D019587:Dietary Supplements; D005247:Feeding Behavior; D005492:Folic Acid; D015971:Gene Expression Regulation, Enzymologic; D006710:Homocysteine / Q000097:blood*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000097:blood / Q000172:deficiency*
chemical_list: D012333:RNA, Messenger; D006710:Homocysteine; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D050940:Betaine-Homocysteine S-Methyltransferase; C494550:Bhmt protein, rat; D015032:Zinc
keywords: Betaine-homocysteine methyltransferase; Gene expression; Homocysteine; Methionine synthase; Zinc