(no subject)

[asimplechord]

I realize this is nit-picking and only someone whose background is in copper/iron/heme metabolism would notice this, but when it comes to heavy and trace metal metabolism/toxicity in the UT medical school curriculum, I think someone somewhere is missing a few basic chemical facts.

Iron?

Not a heavy metal. Not a trace element in biology, either.

ETA: What brought that on? The Chief's annual lecture to med students on heavy metal toxicity and metabolism. Not his area of expertise. Actually, he doesn't really know anything past textbook info about it. But that's what the dept assigned him. So mid-afternoon he called the lab and asked me, "Where is heme made?"

Um, well, all cells with functioning mitochondria and nuclei make heme. Certain steps are mitochondrial, some are cytosolic.

"But where in the body?"

What part of "all cells" wasn't clear? Probably hematopoietic cells make more heme, 'cause that's where hemoglobin gets put into RBCs before they're enucleated, isn't it? But yeah, all cells require heme to function.

"Other than hemoglobin, what is heme needed for?"

Did he want the short list or the long list?

oxygen transport and storage
electron transport
oxidation and hydroxlation of various biomolecules
detoxification of xenobiotics (P450s)
generation of neurotransmitters (NO, CO via HO and NOS)
sterol/hormone biosynthesis
fatty acid metabolism
regulation of anoxia/hypoxia inducible factors via HIF and HAP1

Comments

[topaz7.livejournal.com]

Geebus. I don't know a thing about heme, but I do know when someone's boss is a maroon. Maroon bosses can be identified when they ask you questions you could answer in your sleep.

;)

[asimplechord.livejournal.com]

In his defense, it's not his area of expertise, whereas I spent eight years studying the subject. The department assigns junior faculty med school lectures randomly, and that (along with a lecture on anti-emetics and anti-diuretics, also not his area) was what he got. But yeah, the deptmental strategy makes no sense. Why not use expertise where you have it?

[chiralove.livejournal.com]

heh. D'you see why eukaryotic biology frightens me? I like knowing only two things about iron. :)

[asimplechord.livejournal.com]

But you can pick specific systems in eukaryotes, instead of having to know everything!

For iron, it all comes down to the same thing: Fe²⁺ <=>Fe³⁺ + e, just with different ligands controling the reactivity. Seriously. :)

[chiralove.livejournal.com]

Heh. It doesn't seem that way, sometimes.

Iron: iron-sulfur proteins and siderophores, much fun for pathogens esp. :)

I'm still convinced that y'all are just jealous you don't get to work with bacteria. Come on ... just think of how much faster and easier it is to do things. :)

[asimplechord.livejournal.com]

Ooh, FeS clusters, probably the first use of metal cofactors, chronologically speaking. Rieske clusters, nitrogen fixation, all sorts of hardcore chemistry going on there. And yeah, totally a good target for pathogen-squashing: chelate the iron, stop 'em from growing. Then again, too much chelating also does things like prevent nucleotides from being reduced to the deoxy- forms for DNA synthesis. Damn those clever bugs!

Heh. Even simple eukaryotes use siderophores, though! That is, they can take them up, even though they don't make 'em. Yeast do it, they've got multiple gene products that allow it. Hows that for efficient scavenging?

/science babble.

You have no idea how much I'd love to go back to yeast genetics. So much faster and easier, and you can buy every damn knock-out even if the BY4743 background ResGen used is for shit when it comes to sporulation and non-fermentive growth. Working in human cell lines is a pain in my ass.

[chiralove.livejournal.com]

I've always thought it pretty odd that it took people so long to realize that bacteria aren't selfish little buggers, you know? I mean, a bacteria produces a siderophore and doesn't necessarily get iron back, some other bacteria in the environment might take it up instead. Of course it's kind of super-complicated, thinking of bacteria that way, and yeah ... I guess there's a lot that's gone into evolving our view of them, but it seems so obvious in retrospect, you know?

Squee! I love nitrogen fixation, it's so cool! Shiny and sparkly and oh-so useful. And there's another use for heme there - leghemoglobin. *g*

Is there anything better than the bacterial siderophores? I never really think about it, but I guess I sort of assumed that because they successfully get iron to the pathogen in an iron-limiting environment, the eukaryotes can't beat it ... I mean, but I don't know binding constants or numbers or anything.

Actually I've got no problems at all with yeast. They're practically as good as bacteria - fast-growing, great genetics, reasonably cool ... it's true that they have some unfortunate characteristics, like nuclei and occasionally being diploid, but nobody's perfect, are they?

... Yes, I know that I'm a little bit crazy, but people don't fully appreciate bacteria either, so ... Oh well. Someday everybody will realize how cool bacteria are. :)

[asimplechord.livejournal.com]

N2 fixing is way cool - it involves truly trace metals: vanadium, molybdenum and tungsten, and they make nifty cubane structures.

*wistful sigh*

For enterobactin, I don't know that a true binding constant has ever been determined. It's been a while since I read the papers, but the problem (as I recall it) is that usually such things are determined by a competition, and there's nothing that can out-compete enterobactin for ferric ions, so you can only estimate affinity. So in that respect, I'm not really clear on how chelation therapy actually works, unless the competitor's concentration is so high that it swamps the ENT and prevents and Fe-ENT from binding to the Fep receptors. The other possibility is flooding the system with zinc, which can occupy lots of non-siderophore uptake sites.

Heh. You know, there's a theory in the yeast/metals field that yeast appeared when two bacterial symbionts merged (because of analogies and homologies between mito/rest of cell metal metabolism and E. coli periplasmic metal chaperoning).

[chiralove.livejournal.com]

Heh. You know, there's a theory in the yeast/metals field that yeast appeared when two bacterial symbionts merged (because of analogies and homologies between mito/rest of cell metal metabolism and E. coli periplasmic metal chaperoning)

That is just way too funny ... and too cool! :)