Amity Institute Of Biotechnology

Amity Institute Of Biotechnology

M.Sc (BT)
Enzymes and Enzyme Technology
(GCMB 718)
Dr. Benu Kumar
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Lactate Dehydrogenase(LDH)(E.C.1.1.1.27)
• Lactate dehydrogenase is an oligomeric enzyme
made up of four subunits
• Oxidoreductase enzyme that catalyzes the reversible
reaction of Pyruvate(PA) to lactate(LA) accompanied
by the interconversion of NADH and NAD+.

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• In serum five distinct isoenzymes of LDH exist and are

known as LDH-1, LDH-2, LDH-3, LDH-4, LDH-5.
• Each Isozymes protein is made up of four polypeptide
subunits, thus each is a “tetramer”.
• Each tetramer consists of four sub-units or monomers
each with mass of 36 kDa giving the tetramer the mass of

144 kDa.
• Each monomer consists of a peptide chain of 334 amino
acids with its own active center.
• Each subunit maybe one of two types termed H and M.
• M form predominates in the skeletal muscles and
anaerobic tissues and H form in the heart 3
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• All these isoenzymes catalyze the same reaction but at

different rate.
• The properties of H3M, H2M2 and HM3 being intermediate
between those of H4 ~ and M4 which enables the different
isoenzymes to play different physiological role
• Nathan Kaplan and his colleagues (1964) proposed an
aerobic-anaerobic hypothesis to explain the mechanism
by these isozymes
• Pyruvate may be produced from carbohydrates (by
glycolysis) or from amino acids. Under anaerobic
conditions, it may undergo LDH-mediated conversion to
lactate.
• When oxygen is freely available, pyruvate is metabolized
to enter the tricarboxylic acid cycle. TCA and glycolysis 6
both lead to the synthesis of ATP
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•Under aerobic conditions, most of the pyruvate formed is channelled

into the TCA cycle to ensure maximum ATP production. Tissues which
have plenty of oxygen supply do not normally require much lactate
production to take place and tend to be rich in the H4 isoenzyme.

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• Under anaerobic conditions, the tricarboxylic acid cycle cannot operate,

leaving the cell dependent upon glycolysis for ATP production. Without
a constant supply of NAD+, this too would break down, but the LDH-
mediated conversion of pyruvate to lactate can ensure that NAD+
levels are maintained. Therefore, in tissues which can become oxygen-
starved, an LDH isoenzyme (M4) with a high capacity for converting
pyruvate to lactate is required.
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