Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch, which led to humans having higher UA levels than other mammals. Furthermore, 90% of UA filtered by the kidneys is reabsorbed, instead of bei…
m.rheumatology.oxfordjournals.org

Apart from tackling over-production and under-excretion of uric acid in the management of Gout (and I hope I have convinced you that increasing excretion is the far better way), there is still one more way to treat hyperuricaemia that we have not considered. And that is: to break down uric acid into highly soluble and easily excreted allantoin.
All hominids (we're the only ones left) and the higher primates (gorilla, chimpanzees) lack uricase. We're the only ones who get spontaneous Gout. So, in addition to the host of transporters designed to retain uric acid, we did away with the ability to break it down, shutting off the only escape valve, as it were. Uric acid must be really important to our higher development, perhaps intellectual even, considering the numerous scientific illuminairies throughout history with Gout. I'm in exalted company😉
This is a very intriguing if not philosophical read.


Gout—a disease of red, painful, swollen joints—has an unfair reputation as a disease  that only affects the wealthy after a lifetime of overindulgence. In reality,…
phenomena.nationalgeographic.com|By Ed Yong

While a synthetic uricase, Pegloticase (Krystexxa) exists, we hardly ever use it. It is derived from the pig and baboon, and elicits a rapid and violent immune response which neutralises it at best, or severe allergic reaction at worst.
This article considers the possibility of genetically engineering a prehistoric humanised version of the enzyme.
Perhaps in the future, we can CRISPR edit the promoter site and the main gene to permanently reactivate the uricase gene, and fine tune it just enough to keep Gout at bay and not render us stupid.
That's when Gout is cured.

Evolutionary history and metabolic insights of ancient mammalian uricases

Human susceptibility to gout is driven by the fact that we have a pseudogene for uricase that prevents a functional enzyme from being produced. Our inability to convert highly insoluble uric acid into a more soluble molecule makes us vulnerable to disease ...
ncbi.nlm.nih.gov

No Comments Yet.

Leave a comment