Catalytic Power And Specificity Of Enzymes Biology Essay

Catalytic Power And Specificity Of Enzymes Biology Essay Enzymes are mainly proteins, that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Catalytic power and specificity are the two characteristics of enzymes which require explanation. The structure of the enzymes active site will provide us with the beginnings of an explanation. Since a catalyst must come in contact with the substrate to initiate any reaction, there must be a fit between the substrate and the active site. Right away, some substrate molecules will fit and others will not, so some substrates will react and others will not. The fit can come about either because the molecule fits easily into the enzymes active site (lock-and-key model) or because the enzymes structure adjusts to the substrates entry (induced fit model). Inhibition of enzymes results in a decrease in or elimination of the effect an enzyme has on the rate of a reaction. There are two main types of inhibitors reversible inhibitors and irreversible inhibitors. Reversible inhibitors do not completely stop the enzyme from catalyzing a reaction, and if the concentration of the inhibitor is lowered the enzymatic activity returns to its normal level. The reaction can still proceed but at a much slower rate, depending on the amount of inhibitor and substrate present. If concentrations of the inhibitor are lowered they tend to dissociate from the enzyme. There are three mechanisms for reversible inhibition: Competitive inhibition where the inhibitor resembles the substrate and binds to the same point on the enzyme that the substrate would, Non-competitive inhibition where the inhibitor does not bind to the same point as the substrate but slows down the reaction regardless. Uncompetitive inhibition where the inhibitor binds to the enzyme when the substrate is already bound. Irreversible inhibitors bind strongly to the enzyme usually via covalent bonds and do not dissociate when concentrations are lowered: thus their name. Bonding can occur at the active site or elsewhere on the enzyme, but the overall effect is to inactivate the enzyme. Myocardial infarction Acute myocardial infarction (MI) is defined as death or necrosis of myocardial cells. It is a diagnosis at the end of the spectrum of myocardial ischemia or acute coronary syndromes. Myocardial infarction occurs when myocardial ischemia exceeds a critical threshold and overwhelms myocardial cellular repair mechanisms designed to maintain normal operating function and hemostasis. This is most commonly due to occlusion (blockage) of a coronary artery following the rupture of a vulnerable atherosclerotic plaque, which is an unstable collection of lipids (fatty acids) and white blood cells (especially macrophages) in the wall of an artery. symptoms of acute myocardial infarction include sudden chest pain (typically radiating to the left arm or left side of the neck), shortness of breath, nausea, vomiting, palpitations, sweating, and anxiety (often described as a sense of impending doom). Women may experience fewer typical symptoms than men, most commonly shortness of breath, weakness, a feeling of indigestion, and fatigue. Approximately one quarter of all myocardial infarctions is silent, without chest pain or other symptoms. Treatment of myocardial infarction  · Thrombolytic therapy has been shown to improve survival rates in patients with acute myocardial infarction if administered in a timely fashion in the appropriate group of patients. If percutaneous coronary intervention (PCI) capability is not available or will cause a delay greater than 90 minutes, then the optimal approach is to administer thrombolytics within 12 hours of onset of symptoms in patients with ST-segment elevation greater than 0.1 mV in 2 or more contiguous ECG leads, new left bundle-branch block (LBBB), or anterior ST depression consistent with posterior infarction. Tissue plasminogen activator (t-PA) is superior to streptokinase in achieving a higher rate of coronary artery patency; however, the key to efficacy lies in the speed of the delivery of therapy.  · Aspirin and/or antiplatelet therapy o Aspirin has been shown to decrease mortality and re-infarction rates after myocardial infarction. Administer aspirin immediately, which the patient should chew if possible upon presentation. Continue aspirin indefinitely unless an obvious contraindication, such as a bleeding tendency or an allergy, is present. Clopidogrel may be used as an alternative in cases of a resistance or allergy to aspirin. Recent data from the CLARITY trial (CLopidogrel as Adjunctive ReperfusIon Therapy Thrombolysis in Myocardial Infarction [TIMI] 28) suggest that adding clopidogrel to this regimen is safe and effective. The clopidogrel dose used was 300 mg. Further studies suggest that a higher dose of clopidogrel may have added benefit. o Administer a platelet glycoprotein (GP) IIb/IIIa-receptor antagonist, in addition to acetylsalicylic acid and unfractionated heparin (UFH), to patients with continuing ischemia or with other high-risk features and to patients in whom a percutaneous coronary intervention (PCI) is planned. Eptifibatide and tirofiban are approved for this use. Abciximab also can be used for 12-24 hours in patients with unstable angina or NSTEMI in whom a PCI is planned within the next 24 hours.  · Heparin (and other anticoagulant agents) has an established role as an adjunctive agent in patients receiving t-PA, but not in patients receiving streptokinase. Heparin is also indicated in patients undergoing primary angioplasty. Few data exist with regard to efficacy in patients not receiving thrombolytic therapy in the setting of acute myocardial infarction. Low molecular-weight heparins (LMWHs) have been shown to be superior to UFHs in patients with unstable angina or NSTEMI. Bivalirudin (a direct thrombin inhibitor)  has shown some promise in the setting of STEMI if combined with high-dose clopidogrel load and may be an appropriate alternative strategy.  · Nitrates have no apparent impact on mortality rate in patients with ischemic syndromes. Their utility is in symptomatic relief and preload reduction. Administer to all patients with acute myocardial infarction within the first 48 hours of presentation, unless contraindicated (ie, in RV infarction).  · ACE inhibitors reduce mortality rates after myocardial infarction. Administer ACE inhibitors as soon as possible as long as the patient has no contraindications and remains in stable condition. ACE inhibitors have the greatest benefit in patients with ventricular dysfunction. Continue ACE inhibitors indefinitely after myocardial infarction. Angiotensin-receptor blockers may be used as an alternative in patients who develop adverse effects, such as a persistent cough, although initial trials need to be confirmed.  · Beta-blockers may reduce the rates of reinfarction and recurrent ischemia. Administer to patients with myocardial infarction unless a contraindication is present. However,  a  large chinese trial  showed no benefit to beta-blockade. This has created some doubt as to the benefit  and may lead to a change in the guidelines. Enzyme pattern in myocardial infarction 1. Troponin Normal: Values and units vary from lab to lab Abnormal: Blood levels of troponin I typically rise within 4 to 6 hours after a heart attack reach peak concentrations within 10 to 24 hours, and fall to normal levels within 10 to 15 days. Elevated troponin levels may indicate heart muscle injury Troponin Values 12 hrs after onset of pain: Test Lower limit Upper limit Unit Comments Troponin-T 0.02 ng/mL or ÃŽÂ ¼g/L Upper limit of normal Troponin-I 0.2 ng/mL or ÃŽÂ ¼g/L Upper limit of normal Troponin-T 0.02 0.10 ng/mL or ÃŽÂ ¼g/L Acute Coronary Syndrome Troponin-I 0.2 1.00 ng/mL or ÃŽÂ ¼g/L Acute Coronary Syndrome Troponin-T 0.10 n/a ng/mL or ÃŽÂ ¼g/L Myocardial Infarction likely Troponin-I 1.00 n/a ng/mL or ÃŽÂ ¼g/L Myocardial Infarction likely 2. Creatine kinase  · Myocardial muscle creatine kinase (CK-MB) is found mainly in the heart.  · CK-MB levels increase within 3-12 hours of onset of chest pain, reach peak values within 24 hours, and return to baseline after 48-72 hours.  · Sensitivity and specificity are not as high as for troponin levels.  · Function of Creatine Kinase: A chemical reaction where creatine is converted into phosphocreatine is catalyzed by creatine kinase. This conversion takes place when it applies itself to the utilization of ATP or adenosine triphosphate. Adenosine diphosphate is a basic energy source for brain, skeletal muscle and smooth muscle. Phoshocreatine is an energy reservoir for adenosine diphosphates regeneration. In clinical terms, this enzyme is used as a marker for myocardial infarction which is heart attack and in muscle breakdown by assaying it in blood tests.  · Normal Values for CK, CPK Men 5-100 IU/L Women 10-70 IU/L Pregnancy 5-40 IU/L 3. Lactate dehydrogenase  · Lactate dehydrogenase: (LDH) An enzyme that catalyzes the conversion of lactate to pyruvate. This is an important step in energy production in cells. Many different types of cells in the body contain this enzyme. Some of the organs relatively rich in LDH are the heart, kidney, liver, and muscle.  · Serum lactate dehydrogenase (LAD) level rises above the reference range within 24 hours of a myocardial infarction, reaches a peak within 3-6 days, and returns to the baseline within 8-12 days.  · Normal ranges Test Lower limit Upper limit Unit Comments Lactate dehydrogenase (LDH) 50 150 U/L 0.4 1.7 ÃŽÂ ¼mol/L LDH (enzyme activity) 1.8 3.4  µkat/L 4. Myoglobin  · Myoglobin is found in cardiac and skeletal muscle.  · Myoglobin is a protein in heart and skeletal muscles. When you exercise, your muscles use up any available oxygen. Myoglobin has oxygen attached to it, which provides extra oxygen for the muscle to maintain a high level of activity for a longer period of time.  · When muscle is damaged, myoglobin is released into the bloodstream. Ultimately, it is removed in the urine.  · It is released more rapidly from infarcted myocardium than troponin and CK-MB and may be detected as early as 2 hours after an acute myocardial infarction.  · Myoglobin has high sensitivity but poor specificity. It may be useful for the early detection of myocardial infarction.  · The normal (negative) range is 0 to 85 nanograms per milliliter (ng/mL). Greater-than-normal levels (a positive result) may indicate:  · Skeletal muscle ischemia (blood deficiency)  · Skeletal muscle trauma  · Skeletal muscle inflammation (myositis)  · Heart attack  · Muscular dystrophy  · Rhabdomyolysis  · Malignant hyperthermia (very rare) 5. Natriuretic peptides Studies in several types of acute coronary syndromes have shown that elevated levels of natriuretic peptides. One of the peptides that causes natriuresis, the excretion of an excessively large amount of sodium in the urine. The natriuretic peptides are produced by the heart and vasculature:  · A-type natriuretic peptide is secreted largely by the atrial myocardium in response to dilatation.  · B-type natriuretic peptide is manufactured mainly by the ventricular myocardium.  · C-type natriuretic peptide is produced by endothelial cells that line the blood vessels. B-type natriuretic peptide is useful in the diagnosis of heart failure. The finding of a low level of B-type natriuretic peptide tends to exclude heart failure. 5.a B-type natriuretic peptide (BNP) A 32-amino-acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of myocytes (heart muscles cells) in the ventricles. The levels of B-type natriuretic peptide (BNP) are elevated in patients with left ventricular dysfunction. BNP levels correlate with both the severity of symptoms and the prognosis in congestive heart failure. BNP levels are higher in patients with dyspnea (shortness of breath) due to heart failure than in patients with dyspnea from other causes. Rapid measurement of BNP in the emergency department therefore helps in the evaluation and treatment of patients with acute dyspnea and reduces the time to discharge and the cost of their treatment. BNP appears to be a useful marker of cardiovascular risk, even in people with no clinical evidence of cardiovascular disease. The levels of BNP predict the risk of heart failure, first cardiovascular events, atrial fibrillation, and stroke or transient ischemic attack.