Abstract
BackgroundAerobic 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.MethodsLDH was partially purifiedfrom human breast tumors and normal tissues, which were obtained directly from operating room. TheMichaelis-Menten constant (Km), maximum velocity (Vmax), activation energy (Ea) and enzyme efficiency in breast tumors and normal tissueswere determined.ResultsIt was found that tumor LDH affinity in forward reaction was the same as normal LDH but Vmax 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 Ea of reverse reaction was higher in cancerous tissues.ConclusionsIt 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.
Highlights
Aerobic glycolysis rate is higher in breast cancer tissues than adjacent normal tissues which providethe Adenosine three phosphate (ATP), lactate and anabolic precursors required for tumourgenesis and metastasis
The elution patterns of Lactate dehydrogenase (LDH) showed no significant difference between tumor and normal breast tissues (Figure 1)
The results demonstrated that C-LDH has high affinity to produce lactate in forward reaction while it has low tendency to produce pyruvate in reverse reaction
Summary
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. Excessive growth is an important characteristic of cancer cells. Glycolysis and oxidative phosphorylation are two major metabolism pathways for producing ATP in mammalian cells [2]. Oxidative phosphorylation produces higher ATP from one mole of glucose when compared to glycolysis, many questions remain about the efficiency of these pathways for support of excessive growth in cancer cells. Different mechanisms have been described for glycolysis alteration in cancer cells [6,7]. One possiblereason for this bioenergetics alteration is the release of various enzyme activators or inhibitors, which can change the kinetic properties of enzymes involved in glucose metabolism. Slight attention has been paid to alteration of enzyme kinetic in tumor environment, which can change intrinsic characteristics of enzymes and metabolic pathways
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