CLINICAL CHEMISTRY

CLINICAL ENZYMOLOGY | LIVER ENZYMES

Enzyme Description & Function Clinical Significance Analysis
 Acute Myocardial Infarction
 2 Oxaloglutarate + L-aspartate (in the presence of AST) 
 Begins to Rise 6-8 hrs
L-glutamate + oxaloacetate
 Peak at 24 hrs
Oxaloacetate + NADH + H+(in the presence of Malate
 Normalize within 5 days
dehydrogenase)  L-Malate + NAD.
 3x Increase : Pulmonary Emboli
 Karmen Method- coupled enzyme assay; kinetic assay;
 Slight to Moderate AST ↑
Aspartate rate reaction principle; measures the decrease in
 AST: Transfers amino group from  Acute Pancreatitis
Aminotransferase absorbance; Optimum pH of 7.3-7.8; MDH serves as an
Aspartate to an α-ketoacid  Crushed Muscle Injury
indicator
 Pyridoxal-5’-Phosphate and its amino  Hemolytic Disease
(SERUM GLUTAMIC  Reitman –Frankel- colorimetric method (observation of a
analog pyridoxamine-5’-phosphate  8x AST: Progressive Muscular Dystrophy and Dermatomyositis
OXALOACETIC brown solution| @ 505 nm); reaction with DNPH (ketoacids
serves as coenzymes (Prosthetic  AST ↑ > ALT ↑
TRANSAMINASE) is reacted to 2,4-dinitrophenyl-hydrazine to form ketoacid
Group)  Alcoholic Hepatitis
hydrazines in the presence of NaOH)
 AST/ALT Ratio – reflect grade of  Cirrhosis (4-5x both)
AST | SGOT  Coupling with Diazonium Salts
fibrosis in cirrhotic patients o ratio > (reduced ALT production and reduced AST
5-30 U/L clearance)
Sources of Error:
Elevated
 Liver Neoplasia
Hemolysis, bilirubin, aceto-acetate and n-acetyl compounds, p-
 Primary/Metastatic Carcinoma of Liver (2-5x Both)
aminophenol, sulfthiazole, isoniazid, ascorbic acid, and lipemia
 Mitochondrial-AST in extensive liver cell degeneration and necrosis
Decrease
 Macro-AST no significance
mercury, cyanide and fluoride
 Reduced in UREMIA

 ALT: Transfers amino group from

Alanine  7x ↑ ALT : most efficient for Liver Injury
Alanine to an α-ketoglutarate
Aminotransferase  Reduced in Cirrhosis


 Zinc-Containing  ↑ due to hepatocellular damage

 Six polypeptide chains  2x ↑ : Cirrhosis  NAD+ - preferred coenzyme
 Catalyzes removal of Hydrogen from  4-5x ↑ : Chronic Hepatitis  NADP+ - Hydrogen Acceptor
Glutamate
L-Glutamate to form the  Large ↑: Halothane Toxicity (cause ischemia  centrilobular  Inhibited by Metal Ions (Ag+ and Hg+) Chelating Agents,
Dehydrogenase
corresponding ketimino-acid which necrosis) and L-Thyroxine
undergoes spontaneous hydrolysis to  Together with m-AST, it is used in estimating severity og liver cell  More concentrated on lobules
2-oxoglutarate damage.
  10-12x Elev
 Extrahepatic
Biliary
Obstruction
 Complete
 Catalyzes alkaline hydrolysis of a
Obstrictions
large variery of naturally occurring
 Advnced
and synthetic substances
 ALP Activity in the sera originates mainly Primary Liver
 Liberates inorganic phosphate from
from the Liver ALP with most of the rest Cancer
an organic phosphate ester
from skeleton.  Widespread
 Isoenzymes (Chrom 1)
 Normal to Moderate Elevation Secondary
 Liver
 Infectious hepatitis Hepatic
Alkaline Phosphatase  Bone  Measured in fasting state
 Liver diseases affecting parenchymal Metastases
 Placental
cells  Transient, Benign
 Intestinal
 Reaction to drug therapy Elev in Children
 Renal
 2-3X Elev and infants
 Carcinoplacental ALP (Chrom 2)
 Third Trimester of Pregnancy  ↑ Intestinal ALP
 Regan (Placental)
seen in Liver
 Nagao (Germ Cell)
Cirrhosis
 Kasahara (Fetal Intestinal)
 Bone ALP elev
due to
osteoblastic
activity and bone
diseases
 Acts on Nucleoside-5’-Phosphates  Serum NTP activities reflect hepatobiliary disease with considerable
such as AMP and Adenylic Acid, specificity.
releasing inorganic phosphates  3-6x Elev : Biliary Obstruction
5’-Nucleotidase  Glycoprotein widely distributed  Moderate : Parenchymal Cell Damage as in infectious Hepatitis
principally localized in cytoplasmic  Elevation is very often associated with liver disease even if ALT is
membrane of cells normal.
 Optimum pH is between 6.6 and 7.0  Normal Level of NTP with High ALT indicates Bone Disease
  Small Increase:
Non-Alcoholic
Fatty Liver
Disease
 Transient
Increase: Drug
 Sensitive indicator of hepatobiliary disease
Intoxication  Glycyglycine 5x more effective as an acceptor than glycine
altough not specific of the cause.
 Elevated in or the tripeptide gly-gly-gly
 5-30x Elevation : Hepatobiliary
Alcoholic Hepatitis  Critical for maintainance of intracellular levels of reduced
Obstruction
and those glutathione
 Catalyze transfer of gamma-glutamyl  5-15x: Acute and Chronic Pancreatitis and
receiving  Serum Activity primarily from the liver
γ – Glutamyltransferase group from peptides and compounds malignancies especially if associated with
anticonvulsants  Abundance (Decreasing)
to an acceptor. hepatobiliary obstruction
such as phenytoin 1. Proximal Renal Tubule
 High Elevations:
and phenobarbital 2. Liver
Primary/Secondary(Metastatic) Liver
 Elevated in 3. Pancreas
Neoplasm
Heavy/Chronic 4. Intestine
 Moderate (2-5x) : Infectious Hepatitis
Drinkers
 Acute Myocardial
Infarction Elev on
4th Day, max after
another 4 days

 Dimeric
 Catalyzes nucleophilic addition of
glutathione to the electrophilic  α – GST is released quickly and in large quantities from damaged
centers of a wide variety of chemical hepatocytes into bloodstream.
structures, accomplishing  Evenly distributed across the liver and is released in all types of
Glutathione S-
detoxification reactions hepatocellular damage
Transferase
 Four Main Classes  Valueable than AST in detecting early rejectiion episodes
 α – high conc in liver postoperatively in liver transplants
 µ  Less susceptible to the confounding effects of infections
 π
 ϴ