Transketolase is abundantly expressed in the mammalian cornea by the stromal keratocytes and epithelial cells and is reputed to be one of the corneal crystallins.
These side-chains, specifically Arg359, Arg528, His469, and Ser386, are conserved within each transketolase enzyme and interact with the phosphate group of the donor and acceptor substrates.
[citation needed] Although this enzyme can bind numerous types of substrates, such as phosphorylated and nonphosphorylated monosaccharides including the keto and aldosugars fructose, ribose, etc., it has a high specificity for the stereoconfiguration of the hydroxyl groups of the sugars.
These hydroxyl groups at C-3 and C-4 of the ketose donor must be in the D-threo configuration to correctly correspond to the C-1 and C-2 positions on the aldose acceptor.
[citation needed] In the first half of this pathway, His263 is used to effectively abstract the C3 hydroxyl proton, which thus allows a 2-carbon segment to be cleaved from fructose 6-phosphate.
It is also thought that Asp477 could have important catalytic effects because of its orientation in the middle of the active site and its interactions with the alpha hydroxyl group of the substrate.
Glu418, located in the deepest region of the active site, plays a critical role in stabilizing the TPP cofactor.
Experiments have also been conducted that test the effect of replacing alanine for the amino acids at the entrance to the active site, Arg359, Arg528, and His469, which interact with the phosphate group of the substrate.
[8] In Transketolase Deficiency, also known as SDDHD (Short Stature, Developmental Delay, and congenital Heart Defects), the disease is caused by an inherited autosomal recessive mutation in the TKT gene.
Additional reported features include hypotonia, hyperactivity, stereotypic behavior, ophthalmologic abnormalities, hearing impairment, and variable facial dysmorphism, among others.