Do you like to eat? Because I do. I also like to run, which requires quite a bit of anaerobic metabolism. The combination of the need to break down the glucose in the copious amounts of mashed potatoes I consumed during Sunday dinner and the need to generate large amounts of ATP without the luxury of oxygen makes me a big fan of glycolysis. Going hand in hand with this is my passion for phosphofructokinase-1.
PFK-1 is the most important enzyme in glycolysis. But wait, you say, in order for glycolysis to occur, one needs all of its associated enzymes; it’s impossible for one to be more important than the other. PFK-1, however, catalyzes the committed step of glycolysis, the point of no return. Phosphohexose isomerase does its job, and the rest of the process may or may not occur. PFK-1 shows up to work, though, and you’re guaranteed molecules of that glorious ATP.
Some of you get more pumped about Sunday’s cheesecake than the mashed potatoes (even with the roasted garlic infusion). You are more concerned about fat metabolism than glycolysis. Well, have no fear, young grasshoppers, because PFK-1 plays a role in that as well. As it turns out, PFK-1 regulates triacylglycerol synthesis; mice (and presumably people, though experimentally removing vital enzymes in humans is generally frowned upon) deficient in PFK-1 have decreased fat stores. Wait, you argue, in a country where two thirds of the population is obese, isn’t that a good thing? First of all, I’m guessing that you will change your mind the next time you are starving in the Sahara, far from Aunt Aljean’s green bean casserole. In all seriousness, though, that’s part of what makes PFK-1 so fascinating. Understanding the interplay between PFK-1 and fats has the potential to lead to medical treatments of lipid-related diseases, such as obesity and diabetes.
There are people out there who don’t share my enthusiasm for running, or anaerobic activity in general. A few of you might not even be all that jazzed about eating. How about breathing? Or even just life on the whole? Because even for those of who for whom glycolysis seems a minor annoyance, existing solely to cause lengthy memorization quizzes in Chem 324, PFK-1 is critical. Shutting it down decreases the concentration of later glycolytic intermediates, like 2,3-bisphosphoglycerate. 2,3-BPG increases heme affinity for oxygen, enhancing the body’s oxygen supply. Deficient PFK-1 therefore means difficultly breathing.
Similarly, faulty PFK-1 causes an accumulation of earlier glycolytic intermediates, specifically glucose and glucose-6-phosphate. This results in amplified glycogen synthesis. At first glance, a lot of glycogen may seem pretty inoffensive. Unfortunately, however, it has all kinds of nasty side effects. For example, the increased solute concentration in red blood cells causes water to rush in and the erythrocytes to burst. That’s not good. Also, because the spleen is responsible for recycling red blood cells, it enlarges. That’s no good either. Increased glycogen concentration causes the heart to swell too. The result? Death. That’s really not good.
As you can see, PFK-1 is essential for life. Stuffing fans, apple pie aficionados, runners, couch potatoes, even those of you who just want a refrigerator magnet of a two-subunit protein conveniently colored in your favorite team hues (any Wolverines fans out there?), we all need PFK-1.
Jenkins, Christopher M., Jingyue Yang, Harold F. Sims, and Richard W. Gross. "Reversible High Affinity Inhibition of Phosphofructokinase-1 by Acyl-CoA A MECHANISM INTEGRATING GLYCOLYTIC FLUX WITH LIPID METABOLISM." The Journal of Biological Chemistry 286.1423 Jan. (2011): 11937-50. PubMed. Web. 20 Apr. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21258134>.
Getty-Kaushik, Lisa, Jason C. Viereck, Jessie M. Goodman, Zifang Guo, and Nathan K. LeBrasseur. "Mice Deficient in Phosphofructokinase-M Have Greatly Decreased Fat Stores." Obesity 18.3 Mar. (2010): 434-40. PubMed. Web. 20 Apr. 2011. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871150/>.
Garcia, M, A Pujol, A Ruzo, E Riu, and J Ruberte. "Phosphofructo-1-kinase deficiency leads to a severe cardiac and hematological disorder in addition to skeletal muscle glycogenosis." PLoS Genetics 5.8 Aug. (2009): 1000615. PubMed. Web. 20 Apr. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/19696889>.