Cardiac enzymes 1 – Types, Isoenzymes and structure Lecture NO: 2nd MBBS Dr.Muhammad Ramzan

Cardiac enzymes (CE) – the definition Cardiac enzymes are the proteins that are released into the blood stream when heart muscle is damaged The most common condition is  myocardial infarction (MI). These include CK; CKMB, LDH and AST

Cardiac enzymes - the background Cardiac enzymes are a group of intracellular enzymes that appear in the plasma during normal cell turn over Their level is fairly constant in healthy individuals as: The rate of release from damaged cells is balanced by their removal from the plasma ↑plasma levels of these enzymes may indicate tissue damage like heart, liver and skeletal muscles

Acute Coronary syndrome (ACS) – A pre MI condition Also called as unstable angina It refers to any condition produced by the sudden insuffient blood flow/O2 to the heart via coronaries/branches It may produce unexpected chest pain/pressure/squeezing during rest/sleep/minor physical activity The coronary arteries are partially/completely blocked It Is an acute medical emergency and can lead to MI (30%) There is usually no ST elevation (NSTE) and elevation of Trop./CK

Myocardial infarction/Cardiac Ischaemia major cause of Card. Injury A clinical condition produced by the death of sufficient no: of cardiac myosites due to coronary obstruction The prolonged Ischaemia leads (ACs) to Myocardial necrosis The major cause is Coronary Atherosclerosis that leads to complete obstruction of blood flow and O2 May be due to coronary spasm, embolism and thrombosis

Myocardial infarction/Ischaemia

Myocardial Ischaemia

Cardiac biomarkers- definition the nature and significance Cardiac biomarkers are the substances that are released into the blood when the heart muscle is damaged or stressed. They can detect unstable angina and a small MI 1 Patients with Positive markers are at higher risk for ACS (6:1) compared to the patients with negative ones in follow ups 2 ACS risk is higher with elevated cardiac tropes.

Cardiac markers/biomarkers - the types Cardiac markers are classified into 2 Cardiac enzymes – CK; CKMB, LDH and AST Non enzyme proteins – Troponin (cTnT and cTnI )and others

Cardiac enzymes – The Diagnosis of MI CK and LDH The current trend for the diagnosis of MI is to assess the levels of 2 enzymes including: Creatin Kinase (CK) - CK2 – CKMB and CK Total Lactic Dehydrogenase (LDH) – LDH1 Aspartate Transaminase (AST) - AST

Lactic Dehydrogenase (LDH) and Isoenzymes A group of 5 Isoenzymes LDH is a group of Isoenzymes found in almost all the body cells and helps to produce energy through Glycolysis It causes the conversion of pyruvate to lactate and vice versa during and after metabolism especially in the : Myocardium, Skeletal muscles, liver and Kidneys(renal cortex)

LDH – interconvertion B/W Lactate and Pyruvate in glycolysis

Energy production by pyruvate

LDH – the Isoenzymes. 5 in no: the basis (gene duplication) There are 5 common Isoenzymes of the LDH, from LDH1 LDH5 They are the products of 2 genes producing 2 types of subunits (polypeptide chains- H and M) These subunits combine in 5 different ways to produce intact tetrameric enzyme molecules of LDH The gene for the heart type LDH produces H subunit while the gene for Muscle type LDH produces M subunit

Isoenzymes of LDH (5) - the components Tetrameric Isoenzymes The complete isoenzyme contains 4 subunits (Tetrameric) the predominant tetramer in heart is H4 and: M4 in skeletal muscles. While molecular hybrids of H and M predominate in other tissues Thus, 5 Isoenzymes result from only 2 different genes- duplication LDH1 to LDH5 : H4 ; H3M1, H2M2, H1M3 and M4

Isoenzymes of LDH

Creatine Kinase (CK) – the definition A non protein E It is a non protein enzyme that catalyzes the reversible conversion of Creatine to Creatine phosphate by ATP and : Regeneration of ATP from ADP and Creatine phosphate Is abundantly present in Cardiac/Skeletal muscles and brain

Creatine and ATP interaction the mechanism

CK – the background CK is expressed in tissues that consume ATP rapidly like skeletal muscles; mycocardium,brain and retina It is biomarker of damage for the above tissues and Renal failure Normally; very little Ck is found circulating in the blood. ↑ levels indicate damage to the Cardiac and Skeletal muscles and brain Cr is synthesized from 3AAs Arginine, Glycine and Ornithine/Methionine

Isoenzymes of CK - CK1 to CK3 Dimeric with M and B There are 3 common Isoenzymes of CK from CK1- CK3 They are the products of only 2 genes, producing 2 types of subunits - polypeptide chains M and B These subunits combine in 3 different ways to produce the intact Dimeric enzyme molecules - CK1 to CK3 The gene for muscle type CK produces M subunit while gene for brain type CK produces B subunit Ck1- (CK BB). CK2 (CKMB) - CK3 (CKMM)

Isoenzymes of CK – CK1 to CK3

Aspartate Transaminase AST – the definition It is an enzyme that promotes the reversible transfer of amino group from Glutamic acid to Oxaloacetic acid (for Aspartate) Damage to the heart; liver and brain elevates its blood level

Aspartate Amino Transaminase – AST the background AST is important in the degradation and biosynthesis of AA Glutamate undergoes deamination to form Oxaloacetate and ammonium ions – NH2 is are excreted as urea. Reversibly, Aspartate may be synthesized from Oxaloacetate by adding amino group which is a : key intermediate in citric acid cycle Vitamin B6 (Pyridoxal phosphate) acts as cofactor

AST

Isoenzymes of AST There are 2 Isoenzymes of AST giving rise to 2 polypeptides of AST as a result of gene duplication Cytosolic AST(cAST) : mainly derived from heart and RBC Mitochondrial AST (mAST): mainly from Liver Skeletal muscles

Cardiac enzymes and diagnosis of MI There is no specific Cardiac enzyme/ marker for acute MI with in 6 hours after chest pain but : Immediate treatment has to be started Therefore, Card. enzyme studies must always be compared with symptoms, physical examination findings and : The results of ECG and cardiac imaging(Cardiac Echo/cardiac MRI) Cardiac enzyme studies are often repeated for comparison

Significance of Cardiac enzymes Cardiac enzyme tests are used to assess the present or past Myocardial infarction in an individual 1   It can be used to check the functioning of the heart  after coronary artery bypass graft surgery or angioplasty. 2 (Extent of damage is assessed by the angiography) The enzymes tests are repeated to monitor the progress of the process and management 3