What is the key enzyme of pyruvate kinase pathway

Pyruvate kinase is a key rate limiting enzyme in the glycolysis pathway, mainly involved in the anaerobic breakdown metabolism of glucose, catalyzing the conversion of phosphoenolpyruvate to pyruvate and generating ATP. Its activity directly affects cellular energy supply and is closely related to physiological and pathological processes such as red blood cell metabolism and tumor development.

1. Core role of glycolysis: In the final step of glycolysis, pyruvate kinase catalyzes the transfer of high-energy phosphate bonds from phosphoenolpyruvate to ADP, generating pyruvate and ATP. This reaction is irreversible and releases a large amount of free energy, which is one of the key steps in glycolysis to produce ATP. Enzyme activity is regulated by conformational changes, with fructose-1,6-diphosphate as an important activator.

2. Red blood cell energy metabolism:

Mature red blood cells rely on glycolysis for energy supply. Defects in pyruvate kinase can lead to the accumulation of 2,3-diphosphoglycerate, causing hereditary non spherical hemolytic anemia. Clinical manifestations include jaundice and splenomegaly, which can be diagnosed through red blood cell enzyme activity testing. Severe cases require blood transfusion treatment.

3. Tumor metabolic reprogramming: In the Walden effect of tumor cells, the expression of pyruvate kinase M2 subtype is upregulated, promoting enhanced glycolysis. This isoenzyme can reduce activity through tyrosine phosphorylation, leading to the accumulation of metabolic intermediates and providing biosynthetic materials for tumor proliferation, becoming a target for anti-cancer drug development.

4. tissue-specific distribution:

Mammals have four isoenzymes: PKL liver, PKR red blood cells, PKM1 muscle/brain, and PKM2 embryonic tissue/tumor. PKM2 can regulate enzyme activity through dimer tetramer conversion, and this dynamic change plays a regulatory role in cell proliferation and differentiation.

5. Clinical significance:

Serum pyruvate kinase levels can reflect the degree of cell damage, and are significantly elevated in acute hepatitis and myocardial infarction. Hereditary PK deficiency requires genetic testing. Heterozygous carriers, although asymptomatic, should undergo genetic counseling before marriage and childbirth to avoid the risk of offspring developing the disease.

Maintaining the normal function of pyruvate kinase requires sufficient intake of vitamin B1 and magnesium ions, which are involved in the formation of enzyme active centers. Regular aerobic exercise can promote the expression of PKM1 in skeletal muscle and improve glycolysis efficiency, while limiting high sugar diets can help reduce PKM2 mediated tumor metabolic abnormalities. Patients with red blood cell PK deficiency should avoid oxidative stress, avoid foods that induce hemolysis such as fava beans, and regularly monitor hemoglobin and reticulocyte counts. If couples preparing for pregnancy have a family history, it is recommended to undergo carrier screening. During pregnancy, non-invasive prenatal diagnosis can be used to assess the risk of fetal disease.