title: Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues.
abstract: 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 (Km), maximum velocity (Vmax), activation energy (Ea) 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 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.
  
  
  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.
authors.affiliation: Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Abdolhassan
authors.initials: A
authors.lastname: Talaiezadeh
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shahriari
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Tabandeh
authors.affiliation: Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Fathizadeh
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
authors.forename: Siavash
authors.initials: S
authors.lastname: Mansouri
keywords: Aerobic glycolysis; Breast cancer; Enzyme kinetic; Lactate dehydrogenase