An erythrocyte transketolase isoenzyme pattern associated with the Wernicke‐Korsakoff syndrome

Abstract

Two techniques were used to seek variants of human erythrocyte transketolase and to test for any association of the Wernicke-Korsakoff syndrome, a thiamin-deficiency disease, with a particular variant of this thiamin-dependent enzyme. Apparent Km values for the cofactor thiamin diphosphate were similar for patients and controls. However, isoelectric focussing separated erythrocyte transketolase into different isoenzymes characterized by pI values in the range 6.6-9.2. Six distinct patterns of isoenzymes were found in thirty-six healthy control subjects. The isoenzyme pattern for thirty-nine out of forty-two patients suffering from the Wernicke-Korsakoff syndrome was identical to a pattern found in only eight of thirty-six control subjects, a highly significant association (P less than 0.001). This association suggests that a variant transketolase and thiamin deficiency together contribute to the pathogenesis of the brain damage of the Wernicke-Korsakoff syndrome by some mechanism independent of apparent Km values for thiamin diphosphate.

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

“…Their results were later supported by Mukherjee et al [107] although the observed di erence between the apparent cofactor binding constants for patients and controls was much smaller. In this laboratory TK isolated from erythrocytes of WK syndrome patients and controls did not display any variation in ThDP a nity [113]. It was pointed out that variant apparent K m values may be due to variations in the applied assay conditions given the tight, slow binding of apoTK with the Mg 2+ -ThDP complex [161].…”

“…Multiple bands of isoelectrically focussed TK have also been found in human leukocytes [105] and rat liver [116]. A comparison of the banding patterns of focussed TK isolated from red blood cells of WK syndrome patients and healthy controls led to the report that one particular banding pattern apparently correlates with this disorder [113]. However, Kaufmann et al [75] reexamined the pattern of erythrocyte TK from 63 healthy subjects.…”

Transketolase Is a Major Protein in the Mouse Cornea

“…TKT catalyzes several reactions within the nonoxidative branch of the PP pathway, and together with transaldolase serves as a reversible link between the PP and glycolytic pathways, allowing the cell to adapt to a variety of metabolic needs under changing environmental conditions. TKT is often used to assess thiamine status in man (18), and alterations in TKT chemicophysical or kinetic properties have been implicated in a variety of pathological conditions including Wernicke-Korsakoff's Syndrome (19,20), Alzheimer's disease (21,22), fibromyalgia (23), severe malnutrition (24,25), and alcoholism (26).…”

Thiamine-Responsive Acute Neurological Disorders in Nonalcoholic Patients

“…In the other patients WE appears to be an uncommon complication of common medical conditions (such as hyperemesis of pregnancy, hemodialysis and banded gastroplasy), a fact which also suggests that the development of the disorder depends on a predisposition which may be genetic. It was suggested that altered transketolase activity may predispose patients to alcohol-associated WE [13, 14]but sequencing of the enzyme’s coding region failed to demonstrate a specific variation which may account for an altered enzyme activity [15]. Future advances in the biochemistry and genetics of thiamine-dependent enzymes may define the precise abnormality and set guidelines for appropriate replacement therapy in such patients.…”