Pyruvate kinase
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Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding a pyruvate molecule and producing one molecule ATP.
Contents |
Reaction
The reaction with pyruvate kinase:
pyruvate
kinase
PEP ----------> pyruvate
/ \
ADP ATP
This process also requires magnesium ion. The enzyme is a hydrolase under the international classification of enzymes.
This step is the final one in the glycolytic pathway, which produces pyruvate molecules that can be converted, as acetyl CoA, to ATP.
Regulation
It is also one of the three steps in glycolysis that regulate the activity of the pathway overall, therefore an irreversible reaction that has a high net drop of energy.
Pyruvate kinase activity is regulated by:
- its own substrate PEP and Fructose 1,6-bisphosphate, an intermediate in glycolysis, which both upregulate pyruvate kinase. In so doing, it drives glycolysis to operate faster when more substrate is present.
- citrate and ATP, which allosterically inhibit it. This accounts for parallel regulation with PFK 1.
- Insulin, which activates pyruvate kinase during the fed state by dephosphorylating it (i.e. removing a phosphate group)
- glucagon, which inactivates the enzyme through phosphorylation during fasting when gluconeogenesis occur, so that both processes don't occur simultaneously, resulting in a futile cycle.
- Alanine, which inhibits pyruvate kinase.
Deficiency
Genetic defects of this enzyme cause the disease known as pyruvate kinase deficiency. In this condition, a lack of pyruvate kinase slows down the process of glycolysis. This effect is especially devastating in cells that lack mitochondria, because these cells must use anaerobic glycolysis as their sole source of energy because the TCA cycle is not available.
One example is red blood cells, which in a state of pyruvate kinase deficiency rapidly become deficient in ATP and can undergo hemolysis. Therefore, pyruvate kinase deficiency can cause hemolytic anemia.
Role in gluconeogenesis
Pyruvate kinase also serves as a regulatory enzyme for gluconeogenesis, a biochemical pathway in which the liver generates glucose from pyruvate and other substrates. When pyruvate kinase is inhibited by phosphorylation (which occurs in the fasting state, via glucagon), phosphoenolpyruvate is prevented from conversion to pyruvate. Instead, it is converted to glucose in a series of gluconeogenesis reactions that are mostly (but not exactly) the reverse sequence of glycolysis.
The glucose thus produced is expelled from the liver, providing energy for vital tissues in the fasting state.
External links
Template:Metabolic pathway stub Template:Enzyme-stub
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Phosphotransferases/kinases (EC 2.7) | |
|---|---|
| 2.7.1 - OH acceptor | Hexo- - Gluco- - Fructo- (Hepatic fructo-) - Galacto- - Phosphofructo- (1, 2) - Thymidine - NAD+ - Glycerol - Pantothenate - Mevalonate - Pyruvate - Deoxycytidine - PFP - Diacylglycerol - Bruton's tyrosine - Phosphoinositide 3 (Class I PI 3, Class II PI 3) - Sphingosine |
| 2.7.2 - COOH acceptor | Phosphoglycerate - Aspartate |
| 2.7.3 - N acceptor | Creatine |
| 2.7.4 - PO4 acceptor | Phosphomevalonate - Adenylate - Nucleoside-diphosphate |
| 2.7.6 - P2O7 | Ribose-phosphate diphosphokinase - Thiamine pyrophosphokinase |
| 2.7.7 - nucleotidyl- | Integrase - PNPase - Polymerase - RNase PH - UDP-glucose pyrophosphorylase - Galactose-1-phosphate uridylyltransferase -Terminal deoxynucleotidyl transferase - RNA replicase - Reverse transcriptase (Telomerase) - Transposase |
| 2.7.8 - other phos. | N-acetylglucosamine-1-phosphate transferase |
| 2.7.10-11 - protein | Tyrosine - Serine/threonine-specific |
