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Alkaline Phosphate/ Alkaline Ortosphoric Monoester Phosphohydrolase

A nonspecific enzyme capable of reacting with many different substrates Functions: to liberate inorganic phosphate from an organic phosphate ester with the concomitant production of an alcohol. In healthy sera, alkaline phosphate (ALP) levels derive from liver and bone (osteoblasts) Bone isoenzyme increases due to osteoblastic activity and is normally elevated in children during periods of growth and in adults older than age 50 years (geriatric) In normal pregnancy, increased ALP activity can be detected between 16-20

The presence of intestinal ALP isoenzyme in serum depends on the blood group and secretor status of the individual B or O blood group increases intestinal ALP after consumption of a fatty meal. Major tissue sources: liver, bone, placenta, intestinal, renal Reference values: 30-90 U/L Diagnostic Significance: When total ALP levels are increased, it is the major liver fraction that is most frequently elevatedobstructed jaundice. ALP increase in obstructive jaundice due to greater rate of secretion. For bone disorders, highest elevations occur in Pagets disease (osteitis deformans).

Isoenzymes Liver ALP- most anodal Bone ALP Placental ALP Intestinal ALP- least anodal

Carcino-placental ALP Regan ALP- lung, breast, ovarian, and gynecological cancers, bone ALP comigrator; most heat stable ALP (65C for 30 minutes); inhibited by phenylalanine reagent. Nagao ALP- adenocarcinoma of the pancreas and bile duct, pleural cancer, variant of Regan: inhibited by L-Leucine and phenylalanine.

Notes to Remember: Placental, intestinal, liver and bone- decreasing order of ALP heat stability Heat stability test is performed at 56 C for 10-15 minutesplacental ALP most eat stable; bone ALP most heat labile Placental and intestinal ALP are inhibited by Phenylalanine reagent; 3M urea inhibits bone ALP Levamisole reagent inhibits liver and bone ALP Bowers and McComb (Szaz modification)- IFCC recommended method Hemolysis and diet (fat meals)-sources of analytical errors; elevated serum ALP Sensitive if stored at low temperature (4 C)- leads to increase value ALP is inhibited by phosphorus addition of 2-amino-2methyl-1-propanol (AMP) buffer binds phosphorus under Bowers-McComb method.

Increased ALP Osteitis deformans Obstructive jaundice Osteomalacia Rickets Osteoblastic bone tumors Sprue Hyperparathyroidism Hepatitis and cirrhosis (slight increased) Bone cancer

Acid Phosphatase/ Acid Orthophosphoric Monoester Phosphohydrolase


it catalyzes the same reaction made by ALP, except that it is active at pH 5.0. useful in forensic clinical chemistry, in investigation of rape cases- vaginal washings are examined for seminal-fluid-acid phosphatase (ACP) activity, which can persist for up to 4 days. Diagnostic significance: detection of prostatic carcinoma Tissue Sources: prostate (major source), RBC, platelets and bone Reference values: 2.5-11.7 U/L

Aminotransferas es

an enzyme normally present in body serum and in certain body tissues, especially those of the heart and liver. This enzyme affects the intermolecular transfer of an amino group from aspartic acid to alphaketoglutaric acid, forming glutamic acid and oxaloacetic acid. The reaction is reversible. Aspartate aminotransferase The enzyme is released into from Escherichia coli bound with the serum because of tissue [1] cofactor pyridoxal 5-phosphate. injury and thus may increase as a result of myocardial infarction and it is commonly measured clinically as a Enzymatic reaction: marker for liver + health. Aspartate (Asp) + -ketoglutarate oxaloacetate glutamate (Glu)

AST is similar to alanine transaminase (ALT) in that both enzymes are associated with liver parenchymal cells. Diagnostic Significance: In the evaluation of myocardial infarction, hepatocellular disorders and skeletal muscle involvement In acute myocardial infarction, AST levels begin to rise 68 hours, peak at 24 hours and normalize within 5 days It is released to a greater degree in chronic disorders of the liver with progressive damage.

It has enzymatic activity similar to AST. It catalyses the transfer of an amino group from alanine to -ketoglutarate with the formation of glutamate and pyruvate. The highest concentration is in the liver. More liver specific than AST. Other sources: kidney, pancreas, RBC, heart, skeletal muscle, and lungs.

Diagnostic significance Significant in the evaluation of hepatic disorder. Monitors the course of hepatitis treatment and the effect of drug therapy. ALT measurement is a more sensitive and specific screening test for postt ransfusion hepatitis or occupational toxic exposure. ALT levels are also used to screen blood donors.

Notes to remember:

Aminotransferases require pyrixodal phosphate (vitamin B6) as coenzyme (prosthetic group). Aminotransferases are present in human plasma, bile, CSF and saliva In acute hepatitis, the De Ritis ratio (ALT:AST) is >1.0.

Several viral or toxic hepatitis may produce elevations of transaminases up to 20x the normal limits.
The highest elevations of transaminases in chronic hepatitis, hepatic cancer and infectious mononucleosis.

Slighlty increased in hepatic cirrhosis, alcohol hepatitis and obstructive jaundice.


ALT is slightly increased in obstructive jaundice but markedly increased in necrotic jaundice.

Woff-Parkinson White syndrome

Trichinosis

DermatomyositisAST

Increase Transferases Chronic alcoholism


Toxic hepatitis Acute myocardial infacrtionAST Hepatic Cancer Reyes syndrome Viral Hepatitis

Acute Pancreatitis Muscular dystrophy-AST

An enzyme that hydrolyzes the ester linkages of fats to produce alcohol and fatty acid. It catalyzes partial hydrolysis of dietary TAG in the intestine to the 2-monoglyceride intermediate, with the production of long chain fatty acid Most specific pancreatic marker- secreted exclusively in the pancreas; not affected by renal disorders. Concentrations are normal in conditions of salivary gland involvement. Major tissue source; Pancreas Reference value; 0-1.0U/mL

Diagnostic Significance Diagnosis of acute pancreatitis. It is similar in this respect to AMS measurements but is considered more specific for pancreatic disorders than AMS measurement. Both AMS and LPS levels rise quickly, but LPS elevations persist for approximately 5 days in acute pancreatitis, whereas AMS elevations persist for only 2-3 days. Elevated LPS levels also may be found in other intra-abdominal conditions but with less frequency than elevations of serum AMS. Elevations have been reported in cases of penetrating duodenal ulcers and perforated peptic ulcers, intestinal obstruction, and acute cholecystitis. In contrast to AMS levels, LPS levels are normal in conditions of salivary gland involvement. Therefore, LPS levels are useful in differentiating serum AMS elevation as a result of pancreatic versus salivary involvement.

CREATINE KINASE
ATP- CREATINE-NPHOSPHOTRANSFERASE (CK)

CREATINE KINASE

It catalyzes the transfer of phosphate group between creatine phosphate and adenosine di phosphate Involved in the storage of high-energy creatine PO4 in the muscles. CK-MM is the major isoenzyme (94100%) Bedridden patients may decrease CK activity. Intramuscular injections are known to increase CK (<5x URL ) Ref. Value : Male 15- 160 U/L Female- 15-130 U/L

ISOENZYMES
3 TYPES CK-BB (BRAIN TYPE)

CK-MB ( HYBRID TYPE)

CK-MM (MUSCLE TYPE)

Serum of adults which can be found in the neonatal sera, which contains CK-BB of brain origin due to its high molecular size. Myocardium is the only tissue from which CK-MB enters the serum in significant quantities ( 20% ) CK-MM is both present in the cardiac and skeletal muscles.

DIAGNOSTIC SIGNIFICANCE

It is a very sensitive indicator of acute myocardial infection (AMI) and Duchenne disorder. Total CK is markedly elevated after trauma to skeletal muscle from crush injury, convulsion, tetany, surgical incision or intramuscular injection. Injury in both cardiac and skeletal muscles accounts for the majority of CKMM elevations Demonstration of elevated levels of CKMB, >6% of the total CK, is considered the most specific indicator of myocardial damage.

HISTOPATHOLOGY
Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, affecting around 1 in 3,600 boys, which results in muscle degeneration and eventual death.[1] The disorder is caused by a mutation in the dystrophin gene, located on the human X chromosome, which codes for the protein dystrophin, an important structural component within muscle tissue that provides structural stability to the dystroglycan complex (DGC) of the cell membrane.

DIAGNOSTIC SIGNIFICANCE

Following AMI, the CK-MB levels begins to rise within 4-8 hours, peak at 12-24 hours and normalize within 48-72 hours. CK is not elevated in angina.

PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

INCREASED CREATINE KINASE

Duchennes muscular dystrophy Myocardial Infraction Hypothyroidism Pulmonary infraction Reyes syndrome Strenous exercise and intramuscular injection Cerebral vascular accident (occasional) Rocky mountain spotted fever- CK-MB Carbon Monoxide poisoning

Is a glycolytic enzyme that splits fructose-1,6diphosphate into two triose phosphate molecules in the metabolism of glucose Increased levels: skeletal muscle disease, leukemia, hemolytic anemia, and hepatic cancer

Isoenzymes: Aldolase A-Skeletal Muscles Aldolase B-WBC, liver, kidney Aldolase C-Brain Tissue

a phosponic monoester hydrolase: predominantly secreted from the liver. a marker for hepatobiliary disease and infiltratiy lesions of the liver. methods used: Dixon and Purgon, Campell, Belfield & Goldberg.

it catalyzes the transfer of glutamyl groups between peptides useful in monitoring the effects of abstention from alcohol. or amino acids through linkage at a gammy carboxyl group. it affects the cell membrane and microsomal fractions elevated located among in the canaliculi of undergoing the hepatic warfarin, cells and particularly individuals in the epithelial cells lining the biliary ductules; also in the Phenobarbital and phenytoin therapies. kidney, prostate and pancreas. also increased in pancreatitis and prostatic disorders. useful in differentiating the source of an elevated ALP levels. substrate: y-glutamyl-p-nitroanilide elevated in all hepatobiliary disorders- biliary tract methods used: Szass, Rosalki & Tarrow, Orlowski obstructions. reference values: 5-30 U/L (F)/ 6-45 U/L (M) sensitive indicator of alcoholism (occult alcoholism) most

Index of parachymal function; secreted by the liver.

It is used to monitor the effect of muscle relaxants (succinylcholin e) after surgery.

Also known as peptidyldipeptidase A or Kininase II. It converts angiotensin I to angiotensin II within the lungs. Possible indicator of neuronal dysfunction (Alzheimers disease- CSF) Increased: sarcoidosis, acute and chronic bronchitis and leprosy Main source: macrophages and epitheloid cells

Copper-carrying protein and also enzyme. A marker for Wilsons disease (hepato

For hepatobiliary diseases Reference value: 8-20 mU/mL

It functions to maintain NADPH in the reduced form in the erythrocytes. It is an newborn screening marker. It is found in the adrenal cortex, spleen ,RBC and lymp nodes. Deficiency of this enzyme can lead to drug-induced hemolytic anemia (primaquine,antimalarial drug). Increased levels: myocardial infarction, megaloblastic anemia. Specimen: red cell hemolysate, serum

Reference values: 10-15 U/g