Clinical Enzymology

Rate of entry into blood Serum enzyme activity Rate of removal Inhibition Rate of synthesis Mass of enzyme Producing tissue Tissue damage Clearance Inactivation Factors affecting serum enzyme activity

I- Rate of entry of enzymes into blood is affected by: a – Rate of synthesis of enzyme : - Biliary obstruction   hepatobiliary tree enzymes - Drugs :Anticonvulsant drugs ( Phenobarbital & phenytoin)   synthesis of enzymes by the hepatocytes b- Mass of enzyme producing cells as in: -  alkaline phosphatase: ( in active growth and in 3 rd trimester pregnancy). -  acid phosphatase ( in cancer prostate). c- Necrosis or Cell damage as in: - Hepatitis   transaminases - Myocardial infarction   CK Factors affecting Serum enzyme activities-1

II- Enzyme inhibitors: - Organophosphorus poisoning  irreversible inhibition of cholinesterase. III- Clearance of enzymes: - Breakdown by Proteases and removal by the reticuloendothelial system. - Renal excretion of small molecular enzymes e.g. Amylase Factors affecting Serum enzyme activities-2

Creatine kinase(CK or CPK) گلبول قرمز و کبد فعالیت ندارد

M,B BB(CPK1), MB(CPK2) and MM(CPK3) سالم بیمار

Clinical Significance 1- دیستروفی عضلانی 2- سکته قلبی (3-6 ساعت ) 3- ورزش و ترومای عضلانی 4- رابدومیولیز نرمال در بیماریهای عصبی – عضلانی : میاستنی گراویس و مالتیپل اسکلروزیس

Alanine aminotransferase (ALT) Widely distributed, although the largest amounts found in the liver. Smaller amounts occur in the heart but usually remains normal after MI. More specific for liver disease than AST.

This enzyme is widely distributed in the body. Main sources : Heart, liver, skeletal muscle, and kidney. Useful in the diagnosis of MI, liver disorders and muscle damage. Causes of  serum AST levels: Liver diseases: Hepatitis, hepatic necrosis, cholestasis Cardiac disease: Myocardial Infarction. Diseases of skeletal muscle: Crush injury From Erythrocytes: Hemolysis Aspartate aminotransferase (AST)

Transaminase activities in human tissues, relative to serum as unity ASTALT Heart Liver Skeletal Muscle Kidney Pancreas Spleen Lung Erythrocytes 157 Serum 11

Clinical Significance آلانین ترانسفراز کبدی و اسپارتات ترانسفراز ماهیچه ای – قلبی (6-12 ساعت ) نسبت میتوکندریایی به کل در هپاتیت الکلی آسپارتات میتوکندریایی بالاتر است

میتوکندریایی کبد و عضله قلبی و اسکلتی و گلبول سفید

Hepatocellular damage, chronic hepatitis and less cirrhosis Very large in halothane toxicity other hepato toxic agents

Alkaline Phosphatase(ALP)

+ کبدی - استخوانی - جفتی - روده ای -

Elevations in serum originate from the liver and bone. Hepatobiliary disease and bone disease associated with increased osteoblastic activity Intestinal ALP isoenzyme, an asialoglycoprotein normally cleared by the hepatic asialoglycoprotein receptors, is often elevated in patients with liver cirrhosis.

GGT plays a key role in the gamma-glutamyl cycle a pathway for the synthesis and degradation of glutathione and drug detoxification (L-glutamyl)-peptide + an amino acid peptide + L-glutamyl amino acid

A microsomal enzyme its synthesis induced by ethanol and anticonvulsant drugs. Used primarily for diagnosis of hepatobiliary problems. Marked elevation of serum GGT level is seen in alcoholic liver disease.  serum GGT activity sometimes following MI Gamma-glutamyltransferase (GGT)

GST is an emerging marker for assessing hepatocellular damage. Unlike aminotransferases, GST is released in all types of hepatocyte injury. In liver transplant recipients, GST was found more valuable than AST in detecting early rejection

Converts pyruvate to lactate (and vice versa) during and after anaerobic metabolism. LDH occurs as a tetramer of 2 different subunits: LD-1 (HHHH) from the heart: Elevated after MI. LD-2 (HHHM) from the kidney: Elevated after renal infarction. LD-3 (HHMM) from the lung, spleen and pancreas: Elevated in pulmonary embolism. LD-4 (HMMM) and LD-5 (MMMM), both from the liver and skeletal muscle: Elevated in injury to liver or skeletal muscle. Lactate dehydrogenase (LDH or LD)

Despite its ubiquitous distribution, serum activities to reflect hepatobiliary disease (a stone or tumor occluding the bile duct) When parenchymal cell damage is predominant, as in infectious hepatitis, serum activity is only moderately elevated.

کولین استراز واقعی در گلبول قرمز، ریه، طحال و انتهای اعصاب کولین استراز کاذب در کبد ، سرم ، قلب و پانکراس

Similar to cholinesterase in nervous system, degrades acetylcholine (neurotransmitter and hormone). decrease in hepatitis and cirrhosis. Also decrease in organophosphate (pesticide) poisoning. Degrades succinylcholine, a muscle relaxant given during general anesthesia in surgery. Some people are deficient in plasma cholinesterase, so the normal dose of succinylcholine would kill them Therefore, a determination of plasma cholinesterase is made prior to major surgery. Plasma cholinesterase

Found in prostate, bone, liver, spleen, kidney, RBCs and platelets Primarily used to diagnose prostate cancer .  In other prostatic conditions e.g. prostatitis, benign prostatic hypertrophy. In other non prostatic conditions e.g. hemolysis, metastatic of the breast & Gaucher’s disease. Prostate- Specific Antigen(PSA): an enzyme occurs in prostatic tissue and   in cases of metastatic carcinoma Tartarate inhibits the prostatic ACP enzyme while Formaldehyde inhibits ACP from other sources Acid phosphatase (ACP)