Urate oxidase is found in nearly all organisms, from bacteria to mammals, but is inactive in humans and several other great apes, having been lost in primate evolution. This means that instead of producing allantoin as the end product of purine oxidation, the pathway ends with uric acid.
Uricase is an enzyme that breaks down uric acid to allantoin and is the primary way most mammals regulate their uric acid levels. Our early ancestors also had uricase, but as they lived primarily on fruit, they were still able to eat enough fructose to provide the key energy they needed.
Unfortunately, during the Miocene Epoch, there was global cooling that affected fruit availability, especially during the cooler months, and as the fruit became scarce, many apes starved to extinction.
During this time a mutation in uricase occurred which amplified the uric acid response during fructose metabolism. This provided a survival advantage by resulting in enhanced storage of fat in response to fructose. This mutation, which is present in all humans, amplifies our metabolic responses to fructose compared to most other mammals [1].
Thanks for [1], it made for an interesting read (as well as the Frontiers link within it) since it reminded me of an article [2] in Psychology Today regarding the carnivore diet impact on certain mental-health conditions.
Urate oxidase is found in nearly all organisms, from bacteria to mammals, but is inactive in humans and several other great apes, having been lost in primate evolution. This means that instead of producing allantoin as the end product of purine oxidation, the pathway ends with uric acid.
Uricase is an enzyme that breaks down uric acid to allantoin and is the primary way most mammals regulate their uric acid levels. Our early ancestors also had uricase, but as they lived primarily on fruit, they were still able to eat enough fructose to provide the key energy they needed.
Unfortunately, during the Miocene Epoch, there was global cooling that affected fruit availability, especially during the cooler months, and as the fruit became scarce, many apes starved to extinction.
During this time a mutation in uricase occurred which amplified the uric acid response during fructose metabolism. This provided a survival advantage by resulting in enhanced storage of fat in response to fructose. This mutation, which is present in all humans, amplifies our metabolic responses to fructose compared to most other mammals [1].
[0] https://en.wikipedia.org/wiki/Urate_oxidase#Significance_of_...
[1] https://padiracinnovation.org/News/2020/10/a-hypothesis-link...