Pique the Geek 20110515: Yams and Oral Contraceptives

(8 pm. – promoted by ek hornbeck)

Yams have served as staple foodstuffs in Africa for millenia, having been under cultivation for over 8000 years according to some authorities.  There are dozens of species, but only a relative few are suitable for agriculture.  Yams are members of family Dioscoreaceae and are all of the genus Dioscorea.  Most of them are tropical, but there is one North American species, Dioscorea villosa, aptly called Wild Yam.

Whilst a staple in many tropical areas, yams are not eaten very much in the United States.  What we call a yam is in almost all cases a sweet potato, not closely related to real yams.  It gets even more interesting, since the sweet potato is not a potato at all!  After the fold we shall discuss a different use for yams not involving food.  Since today is 5/15, I though we might start with a bit of music of that name.

This is from Top of the Pops in 1973.  The sound quality is not perfect, but is a nice video.

Now back to yams.  As I said, what we call a yam is actually a sweet potato.  The sweet potato is acutally not a potato at all, since potatoes are members of the order Solanales, the nightshade group, the family Convolvulaceae, and the genus Ipomoea.  This genus comprises the morning glories, so a sweet potato is really a morning glory!  They make attractive house plants, by the way.  Just cut off a piece that has an eye on it, put it in moist potting soil, and before long you will have a vine (it needs support unless you do not mind it running on your floor) and not long after that it will be covered by flowers that look exactly like morning glories, since it is indeed a morning glory.

Yams proper are, as I said, mostly tropical starch crops, but there is another extremely important use for them:  some species are rich sources of the molecular framework that provides essentially all of the steroid group of drugs used in modern medicine similar to these you might find when viewing this steroids Canada vendor or similar.  As a matter of fact, until the 1940s, the only source for steroid drugs was animal sources, usually from beef abattoirs. Drugs like cortisone were thus quite expensive and not nearly as widespread in use as they are now.

The reason is that forming that molecular framework is a huge synthetic challenge.  It can be done, but the cost is enormous.  Here is the reason.

Cortisone

Looking at the structural formula for cortisone, you immediately will notice that it contains four rings fused into a complex.  That is not so hard to do, but there is more.  Remember, single carbon/carbon bonds have a bond angle of right around 109.5 degrees, so this fused ring system is not flat like the formula suggests.  Now do you notice the black wedges?  Ones without any letter at the end of them are methyl (-CH₃ groups pointing towards you.  The wedges with an H mean that only a hydrogen atom, not a methyl group, is pointing towards you.  You will also notice some wedges made with little lines, and that means that the hydrogens are pointing away from you (and in one instance a hydroxy (-OH) group.  The way that these groups and atoms point is critical for drug activity, and if they point in the wrong direction, the drug is useless.

If you look closely, you will see that there are six of these wedges, called in chemistry asymmetric centers.  The syntheses of molecules with asymmetric centers is called stereospecific syntheses, and this is a difficult task.  With six asymmetric centers, you are facing a huge and expensive challenge.

Now you can begin to see just how complex these molecules are.  Since they are so important medically, it is essential to be able to produce them.  Several other steriods are critical in the body, notably testoserone, estrogen, progesterone, and many others.  We make our natural steroids from cholesterol that is produced in the liver and a few other organs from fats in the diet, but the supply of cholesterol is limited.  What was needed was a source of the four ring system with the proper spatial arrangement.  Enter the yam.

It turns out that several yams contain the compound disogenin, a saponin (suds forming material).  It turns out that it contains the four ring system, put together correctly, and can be grown in large quantities.  Here is the structural formula for disoginin:

Disoginin

Note that ALL of the asymmetric centers within the fused ring system are of the correct configuration.  The ones on the parts of the rings that are not fused are much easier to manipulate, such as the one that hold a hydroxy group on cortisone.  In disogenin the oxygen is pointed the wrong way, but since it is not part of the fused system presents little problem.

Mexico developed a large pharmaceutical industry in the 1950s and 1960s due to the yam, and steroid based drugs became commonplace.  As a matter of fact, if it had not been for the yam, oral contraceptives would not have been developed, since those hormones are all steroids.  People who take oral contraceptives are eating yams!  The development of oral contraceptives allowed women (at least in developed countries) for the first time in history to have real control over their reproductive choices, and I believe, as do many sociologists, that this contributed greatly to the societal changes giving women a shot at equal rights (a struggle which is not yet fully realized in developed nations, and not even really started in many parts of the world).

However, there are many other uses for steroid hormones.  The use of hormone replacement therapy for treating menopause is controversial, but still used.  Interestingly, this began with the introduction of the drug Premarin in 1942, long before yam sources had been commercialized.  Premarin is actually a mixture of several estrogen like steroids, and is manufactured from, hold on to your hats, urine from pregnant horses!  If you look at the name of the drug, you can make out Pregnant Mares’ Urine.  As far as I know that particular drug is still made from horse urine, but other products are available that are yam based.

There is a serious medical condition known as Addison’s disease where the adrenal glands for some reason stop producing steroids.  Although steroids are often thought of as something that people take to improve physical strength, only a few steroids have that effect, and they are based on testosterone, the primary male hormone (males also produce estrogen, and females also produce testosterone, just is different relative amounts).  It turns out that steroid hormones are essential in balancing the glucose and mineral levels in the blood, and if your adrenal glands stop making the essential hormones, you shall surely die, unless you get replacements.  The lowly yam has saved countless lives by making these hormones available.  President Kennedy likely would not have lived long enough to be elected if not for this therapy.

There are five major types of steroids (six if you include Vitamin D, ALMOST a steriod), androgens, estrogens, glucocorticoids, mineralocorticoids, and progestagins.  They have quite different functions, and we shall briefly touch upon them.

Androgens are male hormones, the prototype being testosterone.  They promote buildup of muscle mass, facial and upper trunk hair growth, lowering of the pitch of the voice due to a larger larynx (longer vocal cords make for lower pitch), and contribute to aggression.  There are some very potent synthetic ones that are used illegally for body mass increase, and we are all familiar with this.  Women sometimes use them as well, and masculinization is a real possibility.

Estrogens are female hormones, and promote buildup of adipose tissue, retard growth of facial and upper trunk hair growth, and, along with another class of steroids, promote the ability to bear children.  Estrogens are also used in some testosterone dependent cancers, such as prostate cancer, and can cause feminization in patients.  The extremely potent synthetic estrogen, diethylstilbesterol (DES) was given to pregnant women in the 1950s to prevent miscarriage, and had serious effects on male offspring.  By the way, DES is not a steroid, but strongly interacts with the receptors that estrogen does.

Glucocorticoids have a wide range of actions, including glucose regulation, immune response, and mental activity.  These are used in medicine to lower immune response in allergic conditions, asthma, and similar conditions, and are the ones that are given as shots into arthritic joints for pain relief due to reduction of inflammation.  They are available in low concentration ointments for poison ivy and other skin inflammations.  Addision’s disease patients are given these.

Mineralocorticoids  regulate the mineral balance in the blood by their action on the kidney.  Without proper regulation, organisms can not maintain proper blood volume and pressure, so they are essential for life.  Many Addison’s disease patients also receive these.

Progestagins are involved with the estrus cycle in mammals, triggering the onset of menstruation when levels fall.  Since they also inhibit ovulation, they are used (usually in combination with an estrogen) in oral contraceptives.  Some of the newer ones promise to reduce menstruation to only four times per year, since as long as the progestagin levels are high, neither menstruation nor ovulation occurs.

Well, we have gone from yams to oral contraceptives, so I guess this is a good place to stop!  I hope that you got some sense of the importance of steroids in physiology and medicine, and how important it was to have found a source from which these materials can be made at relatively low cost.  Life as we know it would be quite different if these materials were not available, or at such a high cost that wide use could not be made of them.

Well, you have done it again!  You have wasted many more perfectly good einsteins of photons by reading this hard to digest material.  And even though Mike Huckabee admits that it is because he makes way more money than he ever dreampt with his gig at the Fox “News” Channel for him not running for office when he reads me say it, I always learn much more than I could ever hope to teach by writing this series, so keep those comments, questions, corrections, and other feedback coming.  Tips and recs are also happily accepted.  I shall stick around this evening as long as comments warrant, and shall return tomorrow around the same time for stragglers.

Warmest regards,

Doc