The planetary biology of ascorbate and uric acid and their relationship with the epidemic of obesity and cardiovascular disease.
Humans have relatively low plasma ascorbate levels and high serum uric acid levels compared to most mammals due to the presence of genetic mutations in l-gulonolactone oxidase and uricase, respectively. We review the major hypotheses for why these mutations may have occurred. In particular, we suggest that both mutations may have provided a survival advantage to early primates by helping maintain blood pressure during periods of dietary change and environmental stress. We further propose that these mutations have the inadvertent disadvantage of increasing our risk for hypertension and cardiovascular disease in today's society characterized by Western diet and increasing physical inactivity. Finally, we suggest that a "planetary biology" approach in which genetic changes are analyzed in relation to their biological action and historical context may provide the ideal approach towards understanding the biology of the past, present and future.
Johnson
Richard J
RJ
Division of Nephrology, Hypertension and Transplantation, University of Florida, and the Foundation of Applied Molecular Evolution, Gainesville, FL 32610-0224, United States. johnsrj@medicine.ufl.edu
Gaucher
Eric A
EA
Sautin
Yuri Y
YY
Henderson
George N
GN
Angerhofer
Alex J
AJ
Benner
Steven A
SA
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism*; D005075:Biological Evolution; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D004196:Disease Outbreaks; D006801:Humans; D050544:L-Gulonolactone Oxidase / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009765:Obesity / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D011323:Primates / Q000235:genetics / Q000378:metabolism; D014503:Urate Oxidase / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism*
D000975:Antioxidants; D014527:Uric Acid; D050544:L-Gulonolactone Oxidase; D014503:Urate Oxidase; D001205:Ascorbic Acid