Transcription
One of the causes of extravascular hemolysis due to an intracorpuscular problem is pyruvate kinase deficiency. But what is pyruvate kinase? What's that enzyme? That's the topic of today's video. And this is Miracles is Perfection.
Pyruvate kinase is an enzyme in glycolysis. Glycolysis is a process to generate pyruvate as well as ATP, a form of energy, and occurs in the cytosol or the cytoplasm. The red blood cell does not have a mitochondria, so the Krebs cycle as well as the electron transport chain cannot occur in the red blood cell because these processes occur only in the mitochondria.
Let's review glycolysis. We have glucose. Glucose will be converted into glucose-6-phosphate. We need a phosphate; we get it from ATP. ATP will be converted into ADP. This is called hexokinase. Any enzyme with the word “kinase” in it means it will deal with phosphate. Kinase, from kinetic, means movement; so kinase will move a phosphate. Fine. Glucose-6-phosphate to fructose-6-phosphate, then fructose-6-phosphate into fructose-1,6-bisphosphate. This is ATP to ADP because we need one phosphate, and the enzyme will have the word kinase in it. This is phosphofructokinase. Ok. Fructose-1,6-bisphosphate will be converted into glyceraldehyde-3-phosphate, then into 1,3-bisphosphoglycerate, 3-phosphoglycerate, and into 2-phosphoglycerate. There is another pathway for the 1,3-bisphosphoglycerate; it can be converted into 2,3-bisphosphoglycerate and then back to 3-phosphoglycerate. This pathway is very important because any block in this main pathway will lead to an increase of 2,3-bisphosphoglycerate, and as you know, this will shift the oxygen dissociation curve to the right, which means hemoglobin is releasing oxygen to the tissue.
Back to our pathway: 2-phosphoglycerate will be converted into phosphoenolpyruvate. Pay attention here. Phosphoenolpyruvate into pyruvate by pyruvate kinase. Kinase means there is phosphate. Here, 2 ADP will be converted into 2 ATP. Take it to the bank! Whenever there’s kinase, there is phosphate. Pyruvate, and we are done with glycolysis. Pyruvate can be changed into acetyl-CoA, go into the tricarboxylic acid cycle and the mitochondria. This will never occur in the red blood cell because the red blood cell has no mitochondria. Also, another way to generate energy is from the NADH through the electron transport chain, which occurs in the inter-mitochondrial membrane. Again, this will never appear in the red blood cell, which means that glycolysis is the only way by which the red blood cell generates energy. That's fine.
Let's count the ATP here. We have used 2 ATP and we have generated 4 molecules of ATP, so 4 - 2, then it is 2 molecules of ATP. We have gained two molecules of energy. The red blood cell is happy thanks to pyruvate kinase. Imagine what will happen in case of pyruvate kinase deficiency. There is no ATP for the red blood cell. That's why pyruvate kinase deficiency wreaks havoc on the red blood cell. Fine. Also, when this pathway is blocked, 1,3-bisphosphoglycerate will be converted into 2,3-bisphosphoglycerate. High yield. This will shift the oxygen dissociation curve to the right.
I'll see you in the next video with more details on pyruvate kinase deficiency. Be safe, stay happy, and study hard.