LACTATE DEHYDROGENASE

The enzyme lactate dehydrogenase (also known

as lactic dehydrogenase, or LDH) is found in the
cells of almost all body tissues. The enzyme is
especially concentrated in the heart, lier, red
blood cells, kidneys, muscles, brain, and lungs.
LDH helps to produce energy by catalyzing the
reersible reaction between pyruic and lactic
acids. !hen certain conditions in"ure cells in
tissues containing LDH, it is released into the
bloodstream.
Fig. 1. The active site of LDH showing the
relative arrangement of reacting groups.
Fig. 2. A ribbon diagram of the structure of LDH
in the vicinity of the active site. The protein is
shown in gray two Arg residues shown in red
!ADH is shown with its adenosine "yellow#$
pyrophosphate "blue#$ and nicotinamide "green#
moieties.
The total LDH can be further separated into fie
isoenzyme namely#
LDH$% is found mainly in the heart.
LDH$& is primarily associated with the system in
the body that defends against infection
(reticuloendothelial system).
LDH$' is found in the lungs and other tissues.
LDH$( in the kidney, placenta, and pancreas
LDH$) in lier and striated (skeletal) muscle
The relatie amounts of a particular isoenzyme of
LDH in the blood can proide aluable diagnostic
information.
*ormally, leels of LDH$& are higher than those
of the other isoenzymes. +eference alues for
normal leels of LDH isoenzymes can generally
be found within the following ranges#
LDH$%# %,$&,-
LDH$&# &,$',-
LDH$'# %.$&)-
LDH$(# .$%/-
LDH$)# /$%/-.
0ncreased leels of LDH$% are seen in myocardial
infarction, red blood cell diseases like hemolytic
anemia, kidney disease including kidney
transplantation re"ection, and testicular tumors.
0ncreased leels of LDH$& are found in lung
diseases such as pneumonia and congestie
heart failure, as well as in lymphomas and other
tumors. 1leations of LDH$' are significant in
lung disease and certain tumors. 1leations of
LDH$( are greatly increased in pancreatitis. High
leels of LDH$) are found in lier disease,
intestinal problems, and skeletal muscle disease
and in"ury, such as muscular dystrophy and
recent muscular trauma.
2ertain diseases hae classic patterns of eleated
LDH isoenzyme leels. 3or e4ample, an LDH$%
leel higher than that of LDH$& is indicatie of a
heart attack or in"ury5 eleations of LDH$& and
LDH$' indicate lung in"ury or disease5 eleations
of LDH$( and LDH$) indicate lier or muscle
disease or both. 6 rise of all LDH isoenzymes at
the same time is diagnostic of in"ury to multiple
organs.
7ne of the most important diagnostic uses for the
LDH isoenzymes test is in the differential
diagnosis of myocardial infarction or heart attack.
The total LDH leel rises within &($(. hours after
a heart attack, peaks in two to three days, and
returns to normal in appro4imately fie to ten
days. This pattern is a useful tool for a delayed
diagnosis of heart attack. The LDH$% isoenzyme
leel, howeer, is more sensitie and specific than
the total LDH. *ormally, the leel of LDH$& is
higher than the leel of LDH$%. 6n LDH$% leel
higher than that of LDH$&, a phenomenon known
as "flipped LDH" is strongly indicatie of a heart
attack. The flipped LDH usually appears within
%&$&( hours after a heart attack. 0n about .8-
of cases, flipped LDH is present within (. hours
of the incident. 6 normal LDH$%9LDH$& ratio is
considered reliable eidence that a heart attack
has not occurred.
0t should be noted that two conditions might
cause eleated LDH isoenzymes at the same time
and that one may confuse the other. 3or
e4ample, a patient with pneumonia may also be
haing an acute heart attack. 0n this instance,
the LDH$% leel would rise with the LDH$& and
LDH$'. :ecause of this complication, some
laboratories measure only the LDH$% and
consider an eleated LDH leel with LDH$% higher
than (8- to be diagnostic of heart damage.
%ther Factors that can affect LDH Levels
;trenuous e4ercise may raise leels of total LDH,
specifically the isoenzymes LDH$%, LDH$&, and
LDH$). 6lcohol, anesthetics, aspirin, narcotics,
procainamide, fluorides, and mithramycin may
also raise leels of LDH. 6scorbic acid (itamin 2)
can lower leels of LDH.
OTHER SERUM MARKERS AND
DEVELOPMENT:
Myoglobin:
<yoglobin is a protein found in skeletal and
cardiac muscle which binds o4ygen. 0t is a ery
sensitie indicator of muscle in"ury. Howeer, it is
not specific for cardiac muscle, and can be
eleated with any form of in"ury to skeletal
muscle. The rise in myoglobin can help to
determine the size of an infarction. 6 negatie
myoglobin can help to rule out myocardial
infarction. 0t is eleated een before 2=$<:.
(=umar and 2annon, >art 0, &88?)
BNP:
:$type natriuretic peptide (:*>) is released from
entricular myocardium. :*> release can be
stimulated by systolic and diastolic left
entricular dysfunction, acute coronary
syndromes, stable coronary heart disease,
alular heart disease, acute and chronic right
entricular failure, and left and right entricular
hypertrophy secondary to arterial or pulmonary
hypertension. :*> is a marker for heart failure.
(;aenger and @affe, &88,)
CRP:
2$reactie protein (2+>) is an acute phase
protein eleated when inflammation is present.
;ince inflammation is part of atheroma
formation, then 2+> may reflect the e4tent of
atheromatous plaAue formation and predict risk
for acute coronary eents. Howeer, 2+> lacks
specificity for ascular eents. (;aenger and
@affe, &88,)
!i"in: a potentially candidate marker for
myocardial infarction. (&8%()
RE#ERENCES:
3lores, @anis. BLactate Dehydrogenase Test.B Cale
1ncyclopedia of <edicine, 'rd ed.. (&88/).
+etrieed @une %?, &8%( from 1ncyclopedia.com#
http#99www.encyclopedia.com9doc9%C&$
'()%/88?('.html
Harey, +. 6., Harey, +. 6., D 3errier, D. +.
(&8%'). LippincottEs illustrated +eiews#
:iochemistry. >hiladelphia# !olters =luwer
Health9Lippincott !illiams D !ilkins.
Lincoln T6, @oyce C3, (&88?). ;elf$sustained
replication of an +*6 enzyme.
<.<.<. +a"a, 6. +a"a, <.<. 0mran, 6.<.0. ;antha
and =. Deasena, (&8%%). 1nzymes 6pplication in
Diagnostic >rospects. &iotechnology$ 1'( )1*)+.
>orcelli, 6.<., 6. Chelli, 2. 2eccarelli, <. Lang and
C. 2enacchi et al., (&8%8). The genetic and
metabolic signature of oncocytic transformation
implicates H03% destabilization. Human <ol.
Cenet., %?# %8%?$%8'&.
!orthington :iochemical 2orporation. (&8%()
0ntroduction to 1nzymes. <anual of 2linical
1nzyme <easurements %?,&.