The thiamine analogue and advanced glycation endproducts crosslink breaker ALT-711 does not interfere with transketolase activity

Krautwald, Martina, Maxwell, Philippa, Stuchbury, Grant, Holtum, Joe, Burnell, James, and Munch, Gerald (2009) The thiamine analogue and advanced glycation endproducts crosslink breaker ALT-711 does not interfere with transketolase activity. Open Longevity Science, 3. pp. 11-15.

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Abstract

The enzyme transketolase (sedoheptulose-7-phosphate:D-glyceraldehyde-3-phosphate glycolaldehydetransferase, EC 2.2.1.1) is involved in the pentose phosphate pathway (PPP) and catalyses the transfer of a 2-carbon fragment from a 5-carbon keto sugar (xylulose-5-P) to a 5-carbon aldo sugar (ribose-5-P) to form a 7-carbon keto sugar (sedoheptulose- 7-P) and a 3-carbon aldo sugar (glyceraldehyde-3-P). Transketolase requires thiamine pyrophosphate as a co-factor. Advanced glycation endproducts (AGEs) are implicated in the complications of diabetes and aging, primarily via adventitious and crosslinking of tissue proteins. ALT-711 is an AGE crosslink breaker and has been tested as an intervention therapy in established complications of diabetes. It has been noticed that it has a similar structure to that of thiamine and it was hypothesized that it might inhibit transketolase by replacing the active co-factor rendering the enzyme inactive. In this study, we have established a novel microtiter plate format transketolase assay which determines the concentration of NADH by measuring its fluorescence. Using this assay, it was found that ALT-711 does not inhibit the activity of transketolase up to concentration of 5 mM. We conclude that ALT-711 does not interfere with transketolase activity at clinically relevant concentrations.

Item ID: 8407
Item Type: Article (Refereed Research - C1)
Keywords: ALT-711, glycation, crosslink breaker, transketolase, co-factor, thiamine pyrophosphate, carbonyl stress
ISSN: 1876-326X
Date Deposited: 18 Feb 2010 23:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110107 Metabolic Medicine @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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