Triosephosphate isomerase
- OMIM: 109450
- UniProt: P60174
- CAS Number: 9023-78-3
The triosephosphate isomerase (TIM, TPI ) is the enzyme that converts dihydroxyacetone phosphate ( DHAP ) to glyceraldehyde -3- phosphate (GAP ) converts. This is a step of the glycolysis. TPI is therefore essential for all living things, the glucose or fructose can use only via glycolysis.
In humans encodes a gene ( TPI1 ) on chromosome 12, locus 12p13 the functional protein, at least three pseudo genes are known. Mutations in the gene can cause triosephosphate isomerase deficiency.
A potent inhibitor 2 - phosphoglycolate, which is degraded in plants during photorespiration.
Catalysed equilibrium
TPI manufactures a balance between the intermediates dihydroxyacetone phosphate ( DHAP ) and glyceraldehyde -3- phosphate (GAP ). The substrates formed from fructose-1 ,6- bisphosphate in the upstream aldolase reaction. The equilibrium lies strongly on the side of DHAP, for the progress of the CAP, however, glycolysis is required so that the balance shifts by product removal ( Le Chatelier's principle ).
The catalysis via a enediol or enediolate intermediate. This occurs to a glutamate residue ( Glu165 ) in the active site of the enzyme with the unusually high pKa value of 6.5 as a base, a histidine residue ( His95 ) as the acid.
The implementation of GAP to DHAP requires an unusual reaction mechanism in the course of Glu165 an H ion from C- 2 abstracts, while His95 emits a H ion to the C1 atom. This mechanism, since the carboxyl group of Glu is much more acidic ( sour ) than the C2 atom, run under non-enzymatic conditions in any way. The TIM is the ideal scale to the substrate surrounding the active site, however, so-called Low Barrier Hydrogen Bonds ( LBHB ) from a special type of hydrogen bonds, with the -40 to -80 kJ / mol ( instead of about -12 to -30 kJ / mol) are much more stable. This can be achieved by simultaneous LBHB protonation and deprotonation at the carbon atoms C1 or C2.
A 10 amino acid sequence of the enzyme, a so-called loop covers the active site in the substrate loaded. On the one hand so that the enediol intermediate product is stabilized and increase the catalytic activity in this manner by a factor of 105, on the other hand, the escape of this intermediate is avoided - that would dephosphorylate Endiolphosphat and spontaneously rearrange to toxic methylglyoxal.
The TIM is considered as a " perfect enzyme ". This means that changes in the enzyme, of any kind, no more increase in sales bring fortune: The exchange rate of 4300 transactions per second substrate molecule is limited only by the diffusion rates of substrate and product.