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Potential mechanism for hyperhomocysteinemia in Greyhound dogs
Kelsey L Johnson1, Torrey Tiedeman1, Hannah Peterson1
1Department of Medical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Insights
Greyhounds exhibit hyperhomocysteinemia due to a metabolic defect in converting homocysteine to methionine, leading to lower folate and cobalamin levels. This occurs even without intestinal disease signs.
Area of Science:
- Veterinary Medicine
- Canine Metabolism
- Biochemistry
Background:
- Greyhounds are predisposed to hyperhomocysteinemia (HHC), but the metabolic pathways and clinical significance remain poorly understood.
- Investigating HHC in Greyhounds is crucial for understanding canine health and metabolic disorders.
Purpose of the Study:
- To quantify serum homocysteine (HCy) and related metabolites in Greyhounds.
- To elucidate the metabolic pathway contributing to HHC in this breed.
- To assess the association between HHC and oxidative stress markers.
Main Methods:
- Serum HCy, cobalamin, folate, and methionine levels were analyzed in 31 Greyhounds and 15 control dogs.
- Plasma concentrations of cysteine, glutathione, and 8-isoprostane were measured.
- Statistical analysis was performed to compare groups and identify correlations.
Main Results:
- Greyhounds showed significantly higher HCy and lower cobalamin and folate levels compared to controls.
- HCy concentrations were inversely correlated with cobalamin and folate levels.
- No significant differences in plasma cysteine, glutathione, or 8-isoprostane were observed.
Conclusions:
- A primary defect in the conversion of HCy to methionine is suggested in Greyhounds, impacting folate metabolism.
- Inefficient methionine synthase cycling may lead to secondary cobalamin depletion.
- Low folate and cobalamin can occur in Greyhounds irrespective of intestinal disease.
Background:
Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear.
Hypothesis:
Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress.
Animals:
Healthy pet Greyhounds (n = 31) and non-sighthound control dogs (n = 15).
Methods:
Analysis of serum HCy, cobalamin, folate, and methionine, and plasma cysteine, glutathione, and total 8-isoprostane concentrations.
Results:
Homocysteine concentrations were higher in Greyhounds (median, 25.0 μmol/L) compared to controls (13.9 μmol/L; P < .0001). Cobalamin concentrations were lower in Greyhounds (median, 416 ng/L) compared to controls (644 ng/L; P = .004) and were inversely correlated with HCy (r = -0.40, P = .004). Serum concentrations of folate, which is regenerated when HCy is converted to methionine, also were inversely correlated with HCy (r = -0.47, P = .002). Serum methionine concentrations were more than 4-fold lower in Greyhounds (median, 3.2 μmol/L) compared to controls (median, 15.0 μmol/L), but this difference was not significant (P = .3). Plasma cysteine, glutathione, and 8-isoprostane concentrations did not differ significantly between groups.
Conclusions And Clinical Importance:
Our findings suggest a primary defect in conversion of HCy to methionine in Greyhounds, with related impaired folate generation. Ineffective cycling by methionine synthase could lead to secondary cobalamin depletion. Notably, low serum folate and cobalamin concentrations can be observed in Greyhounds without signs of intestinal disease.
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