American Association for Clinical Chemistry
Better health through laboratory medicine
The Mystery Molecule Page: 2004

DECEMBER

Association with this molecule usually leads to destruction but recently it provided three scientists with the Nobel prize in Chemistry. Can you guess what it is?

 

Ubiquitin
One American and two Israelis won for discovering how this small protein is the "kiss of death" for larger proteins that need to be destroyed. Ubiquitin tags them for delivery to the proteasome (a kind of cellular garbage disposal). They named it after finding the molecule in all organisms (it was "ubiquitous").

NOVEMBER

This molecule was recently pulled from the marketplace and is spurring a major investigation into the way the FDA works. Can you guess what it is?

Rofecoxib (Vioxx)
This substituted furanone (the pentagon to the right) is an inhibitor of cyclooxygenase-2 (or COX-2). This version of the enzyme that makes prostaglandins is up-regulated by inflammatory cytokines. Vioxx was a major anti-inflammatory drug until it was pulled amid concerns that it was associated with increased risk of cardiac injury and stroke.

OCTOBER

This molecule interferes with purine synthesis and has a very strange name. Can you guess what it is?

Mycophenolate Mofetil
The mofetil group to the right is a mask, removed after absorption of this oral immunosuppressive drug to reveal mycophenolic acid (the active compound). It inhibits de novo purine synthesis (especially important in lymphocytes) and complements drugs such as cyclosporine and tacrolimus (which inhibit T cell activation).

 

SEPTEMBER

The discoverer of this type of molecule (originally mistakenly believed to come from the prostate gland) recently died. Can you guess what it is?

Prostaglandin
The basic structure of the prostaglandins is shown. The other major derivative of arachidonic acid (leukotrienes) do not have the ring at the left. Sune Bergstrom (who shared the 1982 Nobel Prize in Medicine for discovering the structure of prostaglandins) died in August.

AUGUST

This molecule will be mixed with alcohol (and a slice of lemon) on hot nights this month. Can you guess what it is?

Quinine
Isolated from the bark of the South American quina tree (long known to cure a variety of fevers), this alkaloid became the tonic used by Europeans to combat malaria in Africa and Asia. The British habit of adding a little gin (to overcome the bitter taste) persists today (even if modern-day "tonic water" contains much less quinine and a lot of sugar). It is the basis for the anti-malarial drug chloroquine and the anti-arrhythmic drug quinidine.

 

JULY

The speaker at one of the plenary sessions planned for this month's AACC annual meeting in Los Angeles will be focusing on the way we should report measurement of this molecule. Can you guess what it is?

Creatinine
Dr. Thomas Hostetter discussed the National Kidney Disease Education Program at the last plenary session. Part of this initiative includes asking clinical laboratories to report plasma creatinine results as "estimated" glomerular filtration rates (eGFR) using an equation. The NKDEP believes this will help identify renal disease earlier.

JUNE

Ingesting this molecule regularly has been shown to reduce the risk of cardiovascular disease and cancer (most recently, breast cancer) but many doctors are still unsure about advising patients to do so. Can you guess what it is?

Aspirin
A report last month in the Journal of the American Medical Association found that women who took aspirin once-a-day had a lower risk of developing breast cancer. It is not clear whether aspirin's anti-inflammatory or anti-platelet action (or both) is responsible.

MAY

This molecule is actually two non-covalently bound subunits and cleavage (or "nicking") of the pink loop to the right causes the two subunits to dissociate. Can you guess what it is?

HCG
Human chorionic gonadotropin maintains progesterone production by the corpus luteum during the first two months of pregnancy. After that, the placenta takes over and there is increased inactivation of HCG due to "nicking" of the indicated loop of the beta sub-unit. We hope that all AACC mothers had a happy Mother's Day.

APRIL

 

This molecule, which blocks re-uptake of both serotonin and norepinephrine, may have been responsible for a recent death during a drug trial. Can you guess what it is?

Duloxetine
It sounds like fluoxetine, the most famous selective serotonin reuptake inhibitor (or "SSRI") but this drug also blocks norepinephrine reuptake and is a "SNARI" (serotonin and noradrenergic reuptake inhibitor). The FDA recently issued a warning about both classes of anti-depressant drugs after reports of suicides in patients taking them (especially teenagers).

MARCH

This molecule has a porphyrin ring similar to heme but the divalent cation at the center is magnesium, not iron. Can you guess what it is?

Chlorophyll
The shamrock (or any other plant) wouldn't be green without chlorophyll which absorbs both high-energy violet and low-energy red, using this light to produce glucose from carbon dioxide and water.

FEBRUARY

This molecule will be consumed in great quantity around the middle of the month, stimulating the same receptor in the brain that reacts to marijuana. Can you guess what it is?

Anandamide
This molecule is made naturally in the brain. It is involved in memory and movement control but also stimulates a pleasurable feeling. It is believed that marijuana mimics its action (but, because THC is much more stable, has a greater effect). Anandamide is also found in chocolate. We hope you had a nice Valentine's Day.

JANUARY

This molecule will be left behind when baseball players begin packing for spring training. Can you guess what it is?

Tetrahydrogestrinone (THG)
Adding four hydrogens across the 17-ethynyl group of gestrinone (an androgen used to treat gynecological problems) creates a performance-enhancing steroid which cannot be detected by drug screening. The scandal began last fall, when an anonymous track coach tipped off the agency that conducts testing for Olympic athletes and the drug-testing lab at UCLA identified the substance in previously "negative" urine samples. Thanks to Dr. Larry Bowers for helping us to post this "mystery molecule".