American Association for Clinical Chemistry
Better health through laboratory medicine
The Mystery Molecule Page: 2011

December

This is large molecule described by investigators at University of Missouri is actually two enzymes involved in the oxidation of amino acids joined together. Can you guess what it is?

Molecule of the Month December 2011

Proline Utilization A (Put A)

Oxidation of amino acids, an important part of energy metabolism, usually involves two enzymes. This first forms an intermediate acted on by the second. In humans, these are separate enzymes but in some bacteria these two enzymes are linked together in a large wreath-like complex. The active sites face each other and the substrate is acted on by both in tandem without ever leaving the irregular cavity in between the two. The investigators who crystallized this complex called the space a “subway system for molecules”. We hope everyone enjoyed their holiday season.


 

November

If part of this molecule looks like a wishbone, this may be appropriate as it is suspected of causing the drowsiness one experiences after their Thanksgiving dinner. Can you guess what it is?

Molecule of the Month November 2011

Tryptophan

Tryptophan is an essential amino acid necessary for the production of niacin and some neurotransmitters. It is true that turkey contains a significant amount of tryptophan and that the amino acid (especially if taken on an empty stomach) can cause drowsiness. But you would need to eat almost 10 turkeys to consume enough tryptophan to cause drowsiness, so blaming this amino acid is not fair. More likely, the amount of fat and alcohol (not to mention spending the day on the sofa watching parades and football games) is largely responsible for your “food coma”. We hope you all had a great Thanksgiving.


 

October

This substance would have made Columbus’s voyage to the New World a lot more pleasant than it was. Can you guess what it is?

Molecule of the Month October 2011

Ascorbate (Vitamin C)

Long voyages in the 15th century were plagued by scurvy, a disease caused by vitamin C deficiency. The symptoms were unpleasant (weakness, bleeding and diarrhea) and softening of the gums and loss of teeth made eating difficult. Although many sailors in Asia knew that fresh fruit was a necessary part of the sailor’s diet, these preventatives were largely ignored by Europeans (for a variety of reasons) until Captain James Cook insisted that sailors add sauerkraut to their staple of salted pork and hardtack in the 1770s and showed that this helped prevent scurvy.


 

September

Last month, a federal judge ruled against a generic version of this molecule, one of the fastest-selling drugs in medical history. Can you guess what it is?

Molecule of the Month September 2011

Sildenafil (Viagra ©)

The pharmaceutical company Pfizer developed this drug to treat hypertension but the appearance of spontaneous erections during clinical testing led the company to market it as a treatment for erectile dysfunction. A company with plans to issue a generic version challenged Pfizer’s patent for the latter indication, but was defeated in federal court. Interestingly, Pfizer’s patent for a related drug called Revatio, developed at the same time as Viagra, is only for treatment of hypertension. So when it expires soon, generic versions of this drug may appear (and may be prescribed by some physicians for erectile dysfunction).


 

August

The beach ball you toss around this month (to say nothing of your surfboard, inflatable boat, and bathing suit) is made of a polymer of this molecule. Can you guess what it is?

Molecule of the Month August 2011

Polyurethane

Supposedly invented to circumvent the patent on nylon, the polyurethane monomer has a similar amide structure. But nylon is made by reacting an amine with a carboxylic acid, while polyurethane relies on the reaction of a di-isocyanate with a diol. Polyurethanes are softer and lighter than nylons and, by adding a little tri-isocyanate or triol, a three-dimensional honeycombed structure forms, which we call foam rubber. We hope that you had a happy summer.


 

July

The gene that produces this molecule, which forms part of a genome surveillance complex, will be the focus of the opening plenary at this month’s AACC Annual Meeting in Atlanta. Can you guess what it is?

Molecule of the Month July 2011

BRCA-1

The opening plenary lecture was given by Dr. Mary Claire King, winner of the Walter H. Coulter Lectureship Award. She discussed her discovery of this gene located on chromosome 17 which codes for the protein shown (breast cancer type 1 susceptibility protein). This protein repairs broken DNA, and mutations in the gene produce a greater risk of developing cancer. It joins other similar housekeeping protein to form a large regulatory complex restoring order in the cells genetic material, or killing the cell if order can’t be maintained. The reason for susceptibility to tumors of the breast and ovary (and, in males, prostate) is not clear.


 

June

A delayed release version of this molecule is the latest failure in the attempt to find a drug that raises HDL cholesterol. Can you guess what it is?

Molecule of the Month June 2011

Niacin

Many companies are developing new drugs to raise HDL cholesterol levels because of the association of high HDL with low cardiovascular risk. The “Aim-High” study, in which patients were given an extended-release form of niacin (in order to reduce flushing, a serious side-effect) succeeded in raising HDL levels but did not show any reduction in serious cardiac events. Niacin has been used to try to raise HDL cholesterol for many years, but this was the first large-scale study to try to determine whether this has any effect on cardiovascular outcome.


 

May

This month's AACC webinar discussing antibodies to phospholipids will focus on this protein, sometimes called apolipoprotein H. Can you guess what it is?

Molecule of the Month May 2011

Beta-2-glycoprotein-1

Over a decade ago, this protein was discovered to be necessary for binding of anti-phospholipid antibodies found in patients with “anti-phospholipid antibody syndrome”. Assays specific for the protein may be more helpful than antibodies to phospholipids (such as anti-cardiolipin) in the diagnosis and management of the syndrome. The four identical domains that form the “stem” of the molecule are “complement control protein modules”, also found on a number of complement regulatory proteins (such as C4b-binding protein) and beta-2-glycoprotein-1 may help to tag damaged cells (that abnormally express phospholipids usually kept on the inside of the plasma membrane) with complement so that phagocytic cells can remove them. These modules, with two rims of beta-pleated sheet packing two spirals, are also called “sushi” domains.


 

April

After the damage to nuclear energy plants in Japan last month, bottles containing this crystalline collection of identical molecules flew off the shelves at stores around the world. Can you guess what it is?

Molecule of the Month April 2011

Potassium iodide

Potassium iodide, used as a food additive for nutritional supplementation, may also be taken in large doses to block uptake by the thyroid of 131-iodine, a major by-product of nuclear fission. This may help prevent the development of thyroid cancer in the future, but it cannot prevent radiation poisoning due to other radionuclides also produced during nuclear reactor accidents. In any event, the level of exposure in the U.S. was not believed to warrant such preventative measures.


 

March

Celebrate national nutrition month by examining this representation of a class of compounds, many of which are “essential” elements of a healthy diet. Can you guess what it is?

Molecule of the Month March 2011

Fatty acid

Monocarboxylic acids (the –COOH moiety is on the right of the image) present in the diet usually have an even number of carbon atoms in an unbranched chain (stretching to the left). Saturated fatty acids have no double-bonds in the carbon chain; unsaturated fatty acids may have up to six double-bonds. We can manufacture most of the fatty acids that we need, but those that we cannot are called “essential” fatty acids. The most important is linoleic acid. It is probably no accident that human milk fat is rich in linoleic acid.


 

February

Elevated levels of this molecule are associated with a poor prognosis in people with “broken hearts”. Can you guess what it is?

Mystery Molecule of the Month February 2011

Galectin-3

Galectin-3 is a member of a family of lectins with different specific carbohydrate binding sites (the galactoside recognized by galectin-3 is shown at the bottom of the image). These have a wide array of biological functions but galactin-3 has emerged as a potential marker of congestive heart failure prognosis because it is associated with myofibroblast proliferation. Elevated levels in patients with congestive heart failure may indicate that significant ventricular remodeling is occurring and that they patient’s clinical course if likely to be rocky.


 

January

There was a marked reduction in the number of executions performed in the 35 states with the death penalty in 2010, and a shortage of this molecule may have been a contributing factor. Can you guess what it is?

Mystery Molecule of the Month January 2011

Sodium Pentothal

Modern execution requires three drugs: sodium pentothal, a barbiturate which renders the prisoner unconscious; pancuronium bromide, a muscle relaxant which keeps the prisoner still; and potassium chloride, which causes cardiac arrest and rapid death. Apparently, the increase in propofol use (the drug associated with Michael Jackson’s death) has prompted increase use of sodium pentothal by anesthesiologists, causing a national shortage of this drug.