Pyruvate kinase

• OMIM: 609 712
• UniProt: P30613

Pyruvate kinase (PK) is the enzyme that transfers a phosphate group to ADP, and then provides the energy obtained in the glycolysis as ATP. It is therefore essential in the metabolism of all living beings. While bacteria possess two isoforms of the enzyme, it is in vertebrates four, two each encoded by a gene. In humans, these genes PKLR and PKM2 hot. Mutations in the gene PKLR can cause hemolytic anemia.

The four isoforms are localized in different tissue types: L as the major isozyme in the liver; R in erythrocytes; M1 in muscles, heart and brain; and M2 in the fetus.

Catalysed equilibrium

ADP ATP ⇔

By catalysis, a phosphate group to ADP is transmitted from phosphoenolpyruvate (PEP). There arise ATP and pyruvate. The latter is oxidatively decarboxylated via the pyruvate dehydrogenase complex, to [( acetyl -CoA) ], which is further reduced in the citrate cycle.

Structure

The human pyruvate kinase is a tetramer consisting of four identical protein subunits, each with 528 amino acids. In mammals, there are four isoforms of the enzyme, L or PK2 comes in liver and kidney before, R or PK1 in erythrocytes, M1 or PK3 is found in muscle, heart, brain, leukocytes, and platelets, as well as and M2, which is early, fetal tissues occurs. L and R, and M1 and M2 respectively originate from the same gene but are transcribed by different promoters.

Regulation of pyruvate kinase

Both forms of pyruvate kinase are activated ,6 -bisphosphate by fructose -1. Fructose-1 ,6 -bisphosphate is formed in the third reaction in glycolysis, which is catalyzed by phosphofructokinase. This reaction, known as the committed step is determined by its reaction product, the fructose-1 ,6 -bisphosphate, which acts as an activator for the next reaction in glycolysis and latest, the reaction rate of glycolysis. This regulation allows for homeostasis of the intermediates of glycolysis.

By a high energy charge in the cell (high ATP concentration ) and the presence of alanine inhibits pyruvate kinase. Thus the reaction does not proceed if no additional energy is required by the cell.

The L- isozyme is also controlled by protein phosphorylation. Is the blood glucose level is low, the hormone glucagon causes the phosphorylation of the pyruvate kinase, which thus loses its activity. As phosphoenolpyruvate maintained and available for gluconeogenesis provided, which is constructed by a new glucose in the liver. Also, intracellular calcium can phosphorylate pyruvate kinase.

Pyruvate kinase defects

Only by PKLR allele of pyruvate kinase mutations are known and only the R- form, they show a defect. Lack of PKR is an autosomal recessive metabolic disorder. This hemolytic anemia is often caused because the red blood cells can not produce enough ATP for their diaphragm pumps. Excess of PKR activity with correspondingly increased ATP in blood cells is known as a further defect.