转酮醇酶调控磷酸戊糖代谢和线粒体功能的机制与应用

doi:10.3969/j.issn.1674-8115.2026.02.001

摘要/Abstract

摘要：

转酮醇酶（transketolase，TKT）是磷酸戊糖途径非氧化阶段的关键代谢酶，在原核和真核生物中高度保守。它通过催化2步可逆反应调控三碳糖至七碳糖之间的相互转化。尽管TKT在哺乳动物各种组织中广泛存在，并在多种肿瘤中呈现高表达，但其生理功能和病理意义尚不明确。近期研究发现，肥胖及代谢性疾病（如脂肪肝）普遍存在高胰岛素血症导致的胰岛素抵抗，而TKT表达受高浓度胰岛素诱导上调。TKT是决定细胞磷酸戊糖通量的关键蛋白，它通过介导戊糖代谢物进入糖酵解途径，加速磷酸戊糖分解，降低核苷和核苷酸水平。现有研究揭示了TKT在肝实质细胞、脂肪细胞、调节性T细胞和肝细胞癌中的功能，特别是TKT在调控核苷水平与线粒体功能、核苷酸水平与基因组稳定性、线粒体代谢物水平与DNA甲基化等方面的新机制，为靶向TKT治疗肥胖、脂肪性肝病和肝癌提供了新策略。

关键词: 转酮醇酶, 磷酸戊糖途径, 线粒体, 核苷, 核苷酸

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

中图分类号:

R589.1

汪冠臻, 和文瑞, 童雪梅. 转酮醇酶调控磷酸戊糖代谢和线粒体功能的机制与应用[J]. 上海交通大学学报（医学版）, 2026, 46(2): 137-142.

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.

图/表 2

图1 TKT调控肝实质细胞能量代谢Note： G6P—glucose 6-phosphate; Ru5P—ribulose 5-phosphate; Xu5P—xylulose 5-phosphate; GalNAc—N-acetylgalactosamine. Elevated insulin levels drive hepatic TKT expression, which reduces hepatocyte nucleoside and nucleotide pools, leading to mitochondrial dysfunction and MASH. Targeting hepatocyte TKT with small nucleic acid drugs (GalNAc-siTKT) enhances mitochondrial function and energy expenditure, thereby ameliorating MASH.

Fig 1 TKT modulates energy metabolism in hepatocytes

图2 TKT调控Treg能量代谢及表型Note： TKT deficiency in Tregs not only reduces glycolytic flux but also drives the compensatory mitochondrial import of amino acids and fatty acids, thereby impairing mitochondrial function. Concurrently, the reductive TCA cycle lowers the α-ketoglutarate/succinate and α-ketoglutarate/fumarate ratios, promoting DNA hypermethylation. This suppresses Tregs effector gene expression, ultimately exacerbating autoimmune responses.

Fig 2 TKT regulates energy metabolism and phenotype in Tregs

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