Mechanisms and therapeutic applications of transketolase in regulating pentose phosphate metabolism and mitochondrial function

doi:10.3969/j.issn.1674-8115.2026.02.001

Abstract

Abstract:

Transketolase (TKT) is a key metabolic enzyme in the non‑oxidative phase of the pentose phosphate pathway and is highly conserved across prokaryotes and eukaryotes. It catalyzes two reversible reactions that mediate the interconversion of phosphorylated sugars from three to seven carbons. Although TKT exhibits broad tissue distribution in mammals and is frequently upregulated across diverse malignancies, its definitive physiological roles and pathological implications remain mechanistically unresolved. Recent studies have shown that obesity and metabolic diseases, such as fatty liver disease,are characterized by hyperinsulinemia‑induced insulin resistance, with high insulin levels inducing TKT upregulation. As a master regulator of cellular pentose phosphate flux, TKT channels pentose‑containing metabolites into glycolytic processing, thereby accelerating pentose phosphate catabolism and reducing nucleoside and nucleotide pools. Emerging research has elucidated the roles of TKT in hepatocytes, adipocytes, regulatory T cells, and hepatocellular carcinoma, emphasizing its emerging role in pentose catabolism to coordinate nucleoside homeostasis with mitochondrial function, modulate nucleotide availability and genomic stability, and influence mitochondrial metabolite levels linked to DNA methylation. Collectively, these findings point to TKT as a promising metabolic target, offering novel preventive and therapeutic avenues for obesity, fatty liver disease, and hepatocellular carcinoma.

Key words: transketolase (TKT), pentose phosphate pathway (PPP), mitochondria, nucleoside, nucleotide

CLC Number:

R589.1

Wang Guanzhen, He Wenrui, Tong Xuemei. Mechanisms and therapeutic applications of transketolase in regulating pentose phosphate metabolism and mitochondrial function[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(2): 137-142.

Figures/Tables 2

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References 27

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