The Effect Of Plasma Metabolome Following Dietary Depletion And Supplementation Of Thiamine Pyrophosphate
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1. Metabolomic analysis of changes to plasma metabolome following dietary depletion and supplementation of thiamine pyrophosphate (TPP) in mice
Male C57BL/6J mice (No. 11401300006402), weighing 20 ± 2 g, will be used for this experiment. 7-month old mice will be maintained in a room at 23 ± 2°C and a relative humidity of 50 ± 10%, with a natural light-dark cycle. Food (6 mg thiamine-HCl as the form of TPP) and water will be provided ad libitum. After acclimatization for 1 week, the mice will be divided into two groups (n = 10 in each group) based on dietary difference: the dietary TPP depletion group (no TPP added) and the dietary TPP supplementation group (6 mg thiamine-HCl/kg diet as the form of…show more content… Data interpretation
TPP, the biologically active form of vitamin B1, is an important enzyme cofactor in the mitochondria . In addition, TPP participates as a cofactor of transketolase in the pentose phosphate pathway, a cofactor of the α-ketoglutarate dehydrogenase (α-KGDH), pyruvate dehydrogenase (PDH) and branched-chain α-ketoacid dehydrogenase complex (BCKDC) . Although loss of cofactor can explain in part for loss of enzyme activity, thiamine and its phosphorylated derivatives may also regulate the mediate expression of genes encoding these proteins .
It has been reported thiamine deficiency decreases mRNA levels of transketolase and PDH but not α-KGDH because there was no negative effect of thiamine depletion on at least the E1 subunit of α-KGDH . This may also be explained by an attempt to maintain the activity of one enzyme over the others preferentially, which agrees with riboflavin and enzymes that use it as a cofactor . Therefore, thiamine deficiency may decrease the abundance of acetyl-CoA and ribose, but not affect the abundance of succinyl-CoA. The E1α subunit of the BCKDC participates in the thiamine-dependent decarboxylation of branched-chain α-ketoacids . Therefore, thiamine deficiency may also decrease one of the products of BCKDC, acetoacetate.
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