The always-outstanding neuroblogger, SciCurious, put up an excellent post overnight on a presentation she saw at the current Annual Meeting of the Society for Neuroscience (SfN) in Chicago. Therein, she wrote about a poster presentation she saw on the relationship between iron, cholesterol, and Alzheimer’s disease.
All was quite well until near the end of her post. That is where my writer’s block of the last week dissipated and manifest itself as a blogpost-length comment.
This is a lovely post otherwise but you’ve obviously been drinking if you think you could get away with “an enzyme known as CYP46A1 (yeah, I don’t know what that means either)” knowing that I am reading.
CYP46A1 is a member of the cytochrome P450 family of monooxygenases (look for “CYP” you young whippersnapper; there’s a whole international allele nomenclature org for this). In fact, neuroscientist god and 1970 Nobel laureate, Julius Axelrod in Bernard Brodie’s group first identified this xenobiotic oxidizing system in 1955 – oh, but I’m sorry – you kids don’t read papers before 1966 that aren’t on PubMed because you can’t find the building we used to call a library. Well, rest assured, Dear Weedhopper, that the journal Science has archived their papers online and you can find one of the original papers (Science 121:603-4, 1955 – PDF here) without leaving your computer. Axelrod’s original solo paper is in Journal of Pharmacology and Experimental Therapeutics 114:430-8, 1955.
But, I digress.
While we mostly think of P450s as hepatic, adrenal, renal, or pulmonary enzymes, we’ve known that many other tissues possess P450 activities. CYP46A1 can exist in glia and is otherwise known as cholesterol-24-hydroxylase. The product of this reaction creates a hydroxylated version (at carbon 24 if you can believe it) that cannot cross the blood-brain-barrier as you note.
And while alcohol dehydrogenase is primarily responsible for oxidizing the EtOH coursing through your veins, the higher concentrations you were likely to encounter after writing this post would be handled by CYP2E1. But that all involves things like differences in Km (yeah, I don’t know what that means either.)
Have fun and say hello to all of our friends!
Yes, I closed the comment on a happy note so that she knows I’m just giving her a hard time. However, Sci is fortunate that I am not on her dissertation examining committee.
By the way, this excellent biography of Julius Axelrod by Harry Smith details Axelrod’s relationship as a technician in Brodie’s lab and his pursuit of a PhD at age 42. Axelrod had a tremendous influence on a generation of scientists, including one of my own professors. Smith’s article quotes the philosophy of Axelrod:
- Ask simple questions. (But look beyond the obvious.)
- Do something new, but not too new. (Work just left or right of mainstream questions.)
- Talk to people and read! (Then talk more, read more. You never know where the next idea will come from.)
- Science is 99% discouragement. Stay focused!
- Do one good experiment a day.
- Find and exploit your own scientific style.
- Skimming the cream is a good thing. (But do enough science to know that the cream is real.)
- Don’t sweat the details. Focus on your hypothesis and don’t get swayed by complexity.
- Publish to clarify your thinking and your hypothesis. Nothing more.