Monday, December 05, 2011

Monday's Molecule #152

 
This is a simple molecule so I'm going to insist on the IUPAC name as well as the common name. This time it's not sufficient to just give me the name of the molecule. You also have to briefly explain what it does and why it's important to some humans. The functional explanation has to be a biochemical explanation, not a physiological one.

Post your answer in the comments. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post correct answers to avoid embarrassment.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.) Every undergraduate who posts a correct answer will have their names entered in a Christmas draw. The winner gets a free autographed copy of my book! (One entry per week. If you post a correct answer every week you will have ten chances to win.)

Some past winners are from distant lands so their chances of taking up my offer of a free lunch are slim. (That's why I can afford to do this!)

In order to win you must post your correct name. Anonymous and pseudoanonymous commenters can't win the free lunch.

Winners will have to contact me by email to arrange a lunch date.

UPDATE: The molecule is chlorothiazide of hydrochlorothiazide or 6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide. It's a drug commonly used to treat high blood pressure. Chlorothiazide belongs to a class of drugs that function as diuretics—they decrease blood volume by preventing reabsorption of water from the urine.

The winner is 凌嘉誠 (Alex Ling). His answer emphasizes the role of the drug in inhibiting carbonic anhydrase and that's a valid property. However, the most important immediate effect is probably the inhibition of the Na+/Cl- transporter in the kidneys. As far as I can tell the effects of the drug at the molecular level are not as clear-cut as one would like. The decrease in blood volume appears to be temporary and the long-term effect in lowering blood pressure is probabably due to some unknown effect on veins and arteries.

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: DK
Oct. 31: Joseph C. Somody
Nov. 7: Jason Oakley
Nov. 15: Thomas Ferraro, Vipulan Vigneswaran
Nov. 21: Vipulan Vigneswaran (honorary mention to Raul A. Félix de Sousa)
Nov. 28: Philip Rodger


10 comments :

  1. IUPAC: 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

    AKA Chlorothiazide

    ReplyDelete
  2. Chlorothiazide or 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide. It is an inhibitor of carbonic anhydrase, an enzyme which in the kidney normally acts to create bicarbonate and protons from carbon dioxide and water. The proton gradient created from this is normally used to reabsorb sodium ions from urine via the Na+/H+ antiporter. Moreover, chlorothiazide also interferes with the Na+/Cl- symporter. Administration of chlorothiazide interferes with these processes in the kidney and therefore creates a saluretic effect (salt excretion into urine), which is useful for conditions such as hypertension.

    It's also part of a family of antibiotics (sulfonamides, function self-evident), which interfere with bacterial synthesis of folate by dihydropteroate synthetase. I think you've done a Monday Molecule on prontosil (which I believe I won), but I've summarised both possible answers here.

    My name is 凌嘉誠.

    ReplyDelete
  3. "Chlorothiazide"
    6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide
    (This is named as a sulfonamide, as opposed to a heterocyclic ring...apparently.)

    It's a diuretic, and may be used to lower blood pressure by causing excretion of excess fluids.

    It works by inhibiting Na-Cl symporters in the distal tubules in the kidneys, inhibiting reabsorsion Na and Cl from the urine, and by osmosis, increasing loss of water to the urine.

    I wasn't able to find any information on it's inhibitory mechanism.

    ReplyDelete
  4. "Chlorothiazide"
    6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide
    (This is named as a sulfonamide, as opposed to a heterocyclic ring...apparently.)

    It's a diuretic, and may be used to lower blood pressure by causing excretion of excess fluids.

    It works by inhibiting Na-Cl symporters in the distal tubules in the kidneys, inhibiting reabsorsion Na and Cl from the urine, and by osmosis, increasing loss of water to the urine.

    I wasn't able to find anything on the inhibitory mechanism.

    ReplyDelete
  5. http://en.wikipedia.org/wiki/Hydrochlorothiazide

    Took me a while to hunt it down and you already have winners. So I won't bother a further reply.

    Thanks, it tested my memory from my 30 year old BioChem days...

    ReplyDelete
  6. Patience, Alex, patience. I need time to check out your answer.

    ReplyDelete
  7. Chlorothiazide as carbonic anhydrase inhibitor is an outdated 1950s research. The consensus from later work indicates that its main mechanism of action is inhibition of NaCl transporter.

    ReplyDelete
  8. DK says,

    Chlorothiazide as carbonic anhydrase inhibitor is an outdated 1950s research. The consensus from later work indicates that its main mechanism of action is inhibition of NaCl transporter.

    That doesn't appear to be true from reading the scientific literature but it's often hard to tell what the consensus is unless you're on the inside.

    Part of the problem seems to be that there are many isozymes of carbonic anhydrase. Only one was known in the 1950s but now there are 12 of them and some are involved in regulating ion pumps in the kidney.

    ReplyDelete
  9. That doesn't appear to be true from reading the scientific literature

    I was late to this party and in any way had no idea what the molecule is (other than that it's a drug as indicated by chlorine atom). So for educational purposes I looked up in pubmed what thiazides do and it sure appears to be true that their main mechanism of action is inhibition of NCC. In fact, a synonym for NCCT, where T stands for thiazide-sensitive. NCC null results in the Gitelman syndrome, with all the same symptoms as chlorothiazide effects (except, of course, on a different scale). To the contrary, virtually nothing in the literature on carbonic anhydrase inhibitors suggests that thiazides act through it.

    ReplyDelete