Tag Archives: cancer

Daily Roundup: Introducing Pyruvate Kinase

One of the things that fascinates me the most is the sheer number of delicate, complex biochemical pathways that need to function in order to keep us in working order. Knocking out even one step — getting a protein fold wrong, transcribing a nucleotide base incorrectly — could mean disaster. It’s what leads to sickle cell anaemia, in which the haemoglobin in red blood cells are mis-formed and cannot bind with oxygen as efficiently as usual.

Sickle cell anaemia is caused by the mutation of just a single nucleotide. But there are other equally dramatic changes in the gene to protein pathway that can lead to complications.

One of these is Stanford’s recent research on muscle recovery using a “cooling glove”. It is, according to the researchers themselves, “better than steroids”; one of the scientists, a self-professed gym rat, improved his pull-up rate by 244% in 6 weeks.

The device itself is unremarkable: it’s a thing in the rough shape of a glove which creates a vacuum and draws blood to the palms. Plastic lining in the glove contains water, which cools the palms down.

Described by its own creators as “silly”, the glove works ridiculously well by taking advantage of two fundamental factors of body temperature. The first is the fact that most of the heat in our body is expelled through our face, feet and palms (mostly our palms) in much the same way that dogs expel heat through their tongues.

The second factor is linked to the reason why overheating in the body matters so much. Our bodies — and that of any other animal, really — run on proteins. Haemoglobin is one of these, but there are other, more subtle proteins that control the production of raw energy. The “unit” of energy that serves as a kind of energy currency is ATP, or adenosine triphosphate, which is required in any number of processes in the human body. But ATP and others in the protein family are held together by a delicate, temperature-sensitive balance of chemical bonds. Increase or decrease the ambient temperature too much, and the specific 3D structure of proteins can be critically damaged, depending on how sensitive they are to temperature.

And that’s exactly what happens when our bodies overheat. Muscle pyruvate kinase, or MPK, is responsible for the production of ATP within muscles. Much of the general population can rely on MPK working perfectly fine at any given time, but athletes, who train rigorously and ferociously, need all the help and recovery they can get between bouts of exercise. Overheating an athlete’s body means deforming and deactivating the MPK proteins within it, thus slowing down muscle recovery. But when the muscle cells are cooled down, MPK is basically “reset” and can begin working again.

It’s a beautiful, elegant system that the researchers took advantage of by simply applying the most efficient solution.

But pyruvate kinase’s role in human physiology doesn’t just stop there. MIT researchers discovered a far more crucial role that it could be playing in the production of tumorous growth.

Pyruvate kinase comes into the picture during glycolysis, which produces two molecules of ATP from a molecule of glucose. When one form of pyruvate kinase, called PKM1 is active all the time, the process goes on to produce much more ATP. Tumorous cells, however, express another form of the protein, PKM2, where secondary processes don’t produce as much ATP but go on to produce much more carbohydrates and lipids — essentially, the building blocks of cells. The idea seems to be that normal cells simply need more energy to conduct their normal processes, whereas cancerous cells require more raw material to continue to multiply. A previous study by the same team showed that turning on PKM1 activity in cancerous cells slowed tumorous growth.

What the team is trying to do now is more subtle: to force PKM2, the “abnormal” expression of pyruvate kinase, to operate all the time, “essentially turning it into PKM1”. I must admit I’m not sure how turning on PKM2 is equivalent to turning on PKM1, but in mice implanted with cancer cells and tested with pharmaceutical compounds that turned on PKM2 constantly, the researchers found no evidence of tumorous growth.

It’s pretty fascinating that a single protein is beginning to prove its worth in many ways. I’ll be interested to see what else pyruvate kinase can help with.


Daily Roundup: Living Longer, Better

A little break from the mechanics of the last few posts: yesterday’s news consisted of some startling, and possibly controversial, biological revelations.

It’s been known for a while now that women outlive men, by about five to six years. Looking through some simple statistics, it’s clear that this has been the case as early as 1930, so better living conditions for women and improved access to female healthcare might not tell the whole story. Some scientists in Lancaster University think they have the answer: mitochondrial genetic inheritance.

Mitochondria are tiny organelles believed to have been co-opted by eukaryotic organisms (which includes humans) a couple of billion years ago. Eukaryotic organisms — my high-school biology is slowly returning to me! — are creatures whose internal structures are enclosed and separated by membranes. Most important of these internal structures is the nucleus; prokaryotes lack one, and eukaryotes are defined by it.

Mitochondria are one of the most important of these internal structures. Producers of ATP, the cell’s energy source, they are crucial to cellular health. One of the reasons that mitochondria are theorized to be symbiotic with our bodies is that they actually contain their own version of DNA, with a handful of genes that code for proteins important to respiratory processes, or the production of energy via ATP. The idea of a mitochondrial Eve arose when biologists discovered that every child carries only the mother’s copy of the mitochondrial DNA. There’s no recombination analogous to the meeting of egg and sperm; the entire DNA of the mitochondria is simply handed down from mother to child1.

Scientists from Lancaster conducted a rather interesting study to figure out if this mitochondrial handing-down had any effects on the males as opposed to the females. Using some fruitflies, they determined that variations in mitochondrial DNA seemed to correlate with male life expectancy, while they had no effect on female life expectancy. The idea, if I understand it correctly, is that mutations that are harmful for women don’t accumulate, since natural selection weeds out the women who couldn’t have survived nearly as well. But they may very well have preserved mutations harmful to men. This could mean that the mutations which contribute, in whatever small way, to a smaller male lifespan, would be passed on through generations. The Lancaster researchers argue that the “Mother’s Curse”, which is probably the most frustratingly hyperbolic scientific contraction I’ve heard, would account for reduced male life expectancies.

It’s an interesting hypothesis, but I think I’ll wait for the experiments to be either repeated or something analogous to be discovered in human research. It’s rather too sweeping a realization, especially when combined with the assertion that this could have implications across all species that have similar life expectancy gaps. Does the mitochondrial inheritance work the same way across all of them? If not, what other factors could contribute? This rather well-annotated Wikipedia article indicates that mitochondrial DNA is remarkably slow in accumulating mutations — perhaps once every 3500 years, or 35 human generations. That’s plenty of time to develop mutations harmful to men, but it would be interesting to see where the life expectancy differences began to show up, corresponding to the mutations in DNA.

Another article, this one far more controversial, was the link between persistent cancer and something called “cancer stem cells”. Researchers in three different studies tracked pre-cancerous tumors and found that most of the cell populations in later stages of division had descended from a small subset of the original cell population. In the study conducted by researchers from Belgium, it was reported that the cancer stem cells looked similar to skin stem cells.

At first, the idea of cancerous stem cells seemed rather paradoxical to me. After all, cancer is the result of a small population of cells gone wild, refusing to undergo apoptosis where they trigger a sort of self-destruct mode. But this must begin in some fairly mature, developed, specialized cells of internal organs.  So I’d like to discover how cancerous cells grow and spread across the body, causing the cells of other internal organs to go rogue.

It might be time to do more research — and talk to a graduate student I know…


1.  A whole other interesting tangent is the idea of the “mitochondrial Eve”, the ancestor of most living humans today whose genetic inheritance can be traced in an unbroken line to today’s women. This Wikipedia article gives a little bit of an overview, although more citations are probably needed.

Daily Roundup

At the beginning of this month, I cam across some fantastic sounding news regarding cancer treatments. It’s been known that cancer cells arm themselves with a flag — which the Stanford team persists in calling the “don’t eat me” flag — the way some healthy cells do. If I remember this correctly, red blood cells work with the same antibody.

This meant that the Stanford team that conducted the research could use a protein to mask the expression of this flag, called CD47, thus taking down cancer cells’ defense mechanism. Astoundingly, the cancers implanted in mice either disappeared or reduced significantly. The red blood cells would be targeted as well, since their CD47 flag would be masked as well, but it didn’t seem to leave any lasting damage. In fact, the Stanford study indicates that CD47 is expressed about three times more in some cancer cells as compared to healthy cells. That would mean that the lion’s share of defense-destruction happened with the cancer cells.

Now, I’ve been pointed to an article of a study that suggests that a common virus could be used to target and kill cancer cells. This is incredibly late — by a few years! — which I didn’t realize, but it would be interesting to see why it hasn’t been followed up on.

Other fun stuff, in a completely different field — remember how graphene was meant to be the next big thing in semiconductor technology? And then it… wasn’t? The trouble is that, apparently, even though graphene conducts extremely well, it’s impractical to use for anything requiring switching applications, like transistors. Semiconductors require something called a bandgap, a range of energy during which the they go from being unable to allow any current through to letting current through easily (there’s a much better explanation in Wikipedia, regarding the physics behind it).

And then there was molybdenite, which is very similar to graphene but which actually does have a bandgap in the right spot. Now, researchers in multiple groups have reported being able to synthesize silicene, which is a structure whose existence has been verified through a scanning tunneling electron microscope. It has a unique structure that lets electrons travel in a way that resembles the switching mechanism that transistors need. The trouble will be adapting silicene to the current transistor creation process.

It’ll be fascinating to see which of these alternatives gets developed the most rapidly and efficiently over the next decade, which is when silicon’s limits are predicted to be reached.