Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues

Cancer Cell International

Siavash Mansouri²  Payam Fathizadeh¹  Mohammad Reza Tabandeh²  Ali Shahriari²  Abdolhassan Talaiezadeh¹ 

[1] Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

关键词: Enzyme kinetic;    Lactate dehydrogenase;    Aerobic glycolysis;    Breast cancer;   

Others  :  1138478
DOI  :  10.1186/s12935-015-0171-7

 received in 2014-06-10, accepted in 2015-01-26,  发布年份 2015

【 摘 要 】

Background

Aerobic glycolysis rate is higher in breast cancer tissues than adjacent normal tissues which providethe ATP, lactate and anabolic precursors required for tumourgenesis and metastasis. Lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD⁺, which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH has been found to be highly expressed in breast tumors. Enzyme kinetic characteristics is related to environmentinvolving the enzyme, and tumor microenvironment has distinct features relative to adjacent normal tissues, thus we hypothesized that LDH should have different kinetic characteristics in breast tumors compared to normal breast tissues.

Methods

LDH was partially purifiedfrom human breast tumors and normal tissues, which were obtained directly from operating room. TheMichaelis-Menten constant (K_m), maximum velocity (V_max), activation energy (E_a) and enzyme efficiency in breast tumors and normal tissueswere determined.

Results

It was found that tumor LDH affinity in forward reaction was the same as normal LDH but V_max of cancerous LDH was higher relative to normal LDH. In reverse reaction, affinity of tumor LDH for lactate and NAD⁺ was lower than normal LDH, also enzyme efficiency for lactate and NAD⁺ was higher in normal samples. The E_a of reverse reaction was higher in cancerous tissues.

Conclusions

It was concluded that thelow LDH affinity for lactate and NAD⁺ is a valuable tool for preserving lactate by cancer cells. We also conclude that increasing of LDH affinity may be a valid molecular target to abolish lactate dependent tumor growth and kinetic characteristics of LDH could be a novel diagnostic parameter for human breast cancer.

【 授权许可】

   
2015 Talaiezadeh et al.; licensee BioMed Central.

【 图 表 】

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