Expansion
Different molecular forms of the same enzyme, characteristic of different tissues
Expansion
Definition: different molecular forms of an enzyme catalysing the same reaction, but differing in amino acid sequence, kinetics and tissue distribution.
Clinically used examples
- Creatine kinase: CK-MM (skeletal muscle), CK-MB (cardiac), CK-BB (brain)
- Alkaline phosphatase: liver, bone, placental and intestinal fractions, separable when the source is unclear
- Lactate dehydrogenase: five fractions; LDH1 predominates in heart and red cells, LDH5 in liver and skeletal muscle
- Amylase: pancreatic and salivary fractions
Physiologically important examples
- Hexokinase versus glucokinase: glucokinase has a high Km, so it only acts when glucose is plentiful, which is precisely what allows the liver and the pancreatic beta cell to act as glucose sensors
- Cyclo-oxygenase 1 and 2, the basis of selective NSAID design
The general principle is that tissues express the isoenzyme suited to their metabolic role, and this same specialisation is what allows a blood test to localise damage.
Isoenzyme measurement has been largely superseded for cardiac diagnosis by troponin, but the concept remains central to interpreting alkaline phosphatase and to understanding drug selectivity.