| Mammary EST | Mouse mRNA | Mouse gene | Human RNA | Human gene | Medline | Reference gene |
Pyruvate kinase is an enzyme which catalyzes the 10th reaction in the glycolitic pathway. This reaction is important in that it results in ATP production. Here the phosphoenolpyruvate (PEP) transfers its phosphate to ADP in a substrate-level phosphorilation resulting in ATP formation. This enzyme requires Mg2+ and K+,and the reaction is a site for metabolic regulation. In the liver of vertebrates, the enzyme (molec. weight 250,000), forming a tetreamer, is allosterically inhibited by ATP concentration and is activated by fructose 1,6-bisphoshphate. Pyruvate kinase can increase the cellular activity up to 10 times due to a coresponding increase in the pyruvate kinase production in the liver. The cellular activity also increases due to the intake of carbohydrates. The activity of pyruvate kinase in the liver is also regulated by phosphorylation and dephosphorylation of the protein, the dephosphorylated form being the more active form. All phosphoenolpyruvate produced in muscle is converted to pyruvate. The pyruvate kinase reaction converts the glycolytic pathway from an energy-neutral process to a process which involves synthesis of ATP. The multisubunit enzyme, pyruvate kinase, is inhibited by the ATP, such that high ATP concentration reduces the apparent affinity of the kinase for its substrate (PEP). Another allosteric effect is the feedforward activation (converse of feedback inhibition) of pyruvate kinase due to fructose-1,6-bisphosphate. This ensures that the carbon passing the first regulated step in the pathway will complete the passage through glycolisis avoiding any accumulation of intermediates.
Reference:
Mathews, C., and Van Holde, K.E. 1996. Biochemistry, second edition.
The upper figure represents a Northern blot hybridized with a cDNA probe of approx. 1100 bp. Total RNA from mammry tissue was used for pregnancy and lactation stages from both Stat5a null and wildtype mice. From left to right, the values represent the levels of expression at day 13 of pregnancy, day 1 of lactation in the Stat5a null mice, and day 13 of pregnancy, day 3 of lactation for control mice (wildtype), respectively. Liver total RNA of wildtype mice was used to observe the gene expression in tissues other than the mammry gland. The lower figure represents the hybridization of the same membrane with milk protein controls (WAP and beta-casein).
Laboratory of Genetics and Physiology
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
Bethesda, MD 20892contact: Lothar Hennighausen