Enzymes and Clinical Enzymology Flashcards
A 52 year old man is brought to the emergency room by his wife because of 4 hour history of chest pain. He had a myocardial infarction (MI) two years ago. His ECG does not indicate an acute MI and blood samples are obtained. The serum troponins, total creatine kinase (CK) and CK-MB are estimated in the blood samples. Which of the following best describes the role of these markers?
A. Total serum CK is an injury marker specific for MI
B. Increase of serum CK-MB but not of total CK indicates rhabdomyolysis
C. Serum CK-MB larger than 3% of total serum CK can indicate an acute MI
D. A low ratio of CK-MB to total CK indicates a severe MI
E. Serum levels of CK-MB but not total serum CK are increased after an acute MI
C. Serum CK-MB larger than 3% of total serum CK can indicate an acute MI
A 28 year old woman is brought to the emergency department with a 5 hour history of chest pain. A provisional diagnosis of myocardial infarction is made. An ECG is performed and blood is drawn for the measurement of various injury markers. Which of the following biomarkers would be most useful at this time to confirm the diagnosis?
Troponin-I
A 25 year old man comes to the physician because of a 2 week history of weakness while climbing stairs. Physical examination shows bilateral atrophy of the quadriceps and calves and diagnosis of skeletal muscle dystrophy is made. Laboratory studies show high levels of serum creatine kinase (CK). Which of the following best describes this enzyme?
Uses creatine phosphate as a substrate during muscle contraction.
A 25 year old woman comes to the physician because of a 3 day history of abdominal pain, loss of appetite and fever. Physical examination shows right upper abdominal tenderness and jaundice. A provisional diagnosis of acute liver disease is made. Blood samples are obtained for marker analysis. Elevation of which of the following enzyme levels would most likely confirm the diagnosis in this patient?
Alanine aminotransferase (ALT)
A 50 year old man is prescribed a low-dose of aspirin (81 mg/day) to prevent cardiovascular disease. Aspirin (acetyl salicyclic acid) is an irreversible enzyme inhibitor. Which of the following enzymes is most likely inhibited by this drug?
A. Acetylcholinesterase
B. Thromboxane synthase
C. HMG CoA reductase
D. Xanthine oxidase
E. Cyclooxygenase
Cyclooxygenase
A 65 year old woman has mild cardiovascular disease and is prescribed low-dose aspirin daily to reduce her blood clotting. Which of the following best describes the rationale for this treatment?
Reduces synthesis of thromboxane
A research group investigates an allosteric enzyme which does not follow Michaelis-Menten kinetics. Kinetics of the enzyme is plotted with the velocity on the Y-axis and the substrate concentration on the X-axis. Which of the following best describes the kinetics of this enzyme?
Sigmoidal due to a cooperative effect of the substrate.
A research group investigates the isozymes of creatine kinase and lactate dehydrogenase as possible serum markers in patients with myocardial infarction. Which of the following best describes the use of LDH in these patients?
LDH1/LDH2 ratio increases following an infarction
With a provisional diagnosis of acute pancreatitis, which of the following laboratory findings would most likely confirm this diagnosis?
High lipase: amylase ratio.
A research group investigates the regulation of a specific enzyme of intermediary metabolism. It is observed that the enzyme is regulated by phosphorylation by protein kinase A. Which of the following amino acid residues in the enzyme is most likely modified in this type of regulation?
A. Tyrosine
B. Glutamate
C. Serine
D. Methionine
E. Asparagine
Serine
A research group investigates the regulation of an enzyme of the glycolysis pathway. It is observed that the enzyme activity is regulated by the presence of allosteric modulators. It is observed that addition of a modulator results in feedback inhibition of the enzyme. Which of the following best describes this modulator?
Decreases enzyme affinity for its substrate
A research group investigates the role of creatine phosphate in skeletal muscle tissue. Which of the following best describes this intermediate?
Formed by creatine kinase when [ATP] levels are high.
A research group studies the reaction catalyzed by trypsin for general study of enzymology. Which of the following best describes this enzyme?
Activity is dependent on the pH of the medium
Glycogen Synthase
Glycogen synthesis
Phosphorylase b kinase
Glycogen breakdown
Pyruvate kinase
Glycolysis
Pyruvate dehydrogenase complex (type L)
Pyruvate to acetyl-CoA
Hormone-sensitive lipase
Triacylglycerol mobilization and fatty acid
Phosphofructokinase-2/fructose 2,6-bisphosphatase
Glycolysis/gluconeogenesis
Tyrosine hydroxylase
Synthesis of L-DOPA, dopamine, norepinephrine, and epinephrine
Histone H1
DNA condensation
Histone H2B
DNA condensation
Cardiac phospholamban (a cardiac pump regulator)
Regulation of intracellular (Ca2+)
Protein Phosphatase-1 inhibitor-1
Regulation of protein dephosphorylation
CREB
cAMP regulation of gene expression
ADP-ribosylation
Addition of ADP-ribose: inactivation of proteins
Cholera toxin
ADP-ribosylates G-alpha-s: Continuously active G-alpha-s
-Increased cAMP in intestinal mucosal cells
-Opening of CFTR: loss of electrolytes and water: severe watery diarrhea
Pertussis toxin ADP-ribosylates G-alpha-i
Continously inactive G-alpha-i:
-Increased cAMP in respiratory-tract cells
-Respiratory distress, and whooping cough
Phosphoinositide system
-Second Messengers are IP3, DAG, Ca2+
1. Epinephrine binds to alpha1-adrenergic receptor
2. Activates Gq-alpha which binds to GTP (in exchange for GDP)
3. Gq-alpha-GTP activates phospholipase C (PLC)
4. PLC cleaves PIP2 to IP3 and DAG
5. IP3 causes Ca2+ release from endoplasmic reticulum
6. DAG and Ca2+ activate Protein Kinase C for cellular responses
-PKC requires DAG, Ca2+ and phospholipids (membrane)
Cholinergic muscarinic receptors activate:
Phospholipase C isoform to form IP3, DAG, and Ca2+
cGMP
Second messenger in smooth muscle relaxation, platelet aggregation and in visual system
Nitric Oxide
Gaseous form: synthesized from Arginine
-Synthesized in endothelial cells where it diffuses to vascular smooth muscle where it activates cytosolic guanylate cyclase
-Activation of cholinergic (muscarinic) receptors in the endothelium by acetylcholine
-Increases cGMP
-Activation of PKG and subsequent muscle relaxation
Creatine Kinase (CK) isozymes
In serum are used as injury markers: CK contains the 2 subunits B and M which leads to 3 isozymes:
-CK-BB (CK-1)
-CK-MB (CK-2)
-CK-MM (CK-3)
What is the creatine kinase found in the brain?
CK-BB: sCK-BB is elevated after CNS damage.
Heart Muscle creatine kinase
Has the highest % of CK-MB: 30% CK-MB and 70% CK-MM
-These injury markers are elevated after myocardial infarction.
Skeletal muscle creatine kinase
Has 98% CK-MM and 2% CK-MB
-sCK-MM is elevated in rhabdomyolysis or muscular dystrophy
Timeframe for serum MI markers
CK-MB level peaks after 24 hours. LDH level peaks later after 48 hours.
Criteria for indication of an MI
1) The CK-MB/total CK ratio is >6%
2) The CK-MB/total CK ratio is >3% and troponins are increased
Troponins
Proteins involved with muscle contraction with specific isoforms:
1) Cardiac Troponin I (cTnI: Inhibition of actomyosin ATPase)
2) Cardiac Troponin T (cTnT: Tropomyosin binding)
A patient is admitted to hospital because of an acute myocardial infarction. His serum injury markers are measured at admission and then at 4-hour intervals The data for myoglobin, CK-MB and cTn are combined in one graph showing the time-line following the infarction. How is the curve for serum CK-MB best described and compared to myoglobin and cardiac troponins?
CK-MB shows a sharp peak following myoglobin
A 60 year old male patient is admitted to the ER Department with substernal chest pain, tachycardia, diaphoresis and irritability. Upon examination of the patient, ECG and further laboratory evaluation; it was found that he has a STEMI. Which one of the cardiac biomarkers will return to baseline with 7-10 days?
Troponins.
Liver Function Tests
Ammonium (high)
Albumin (reduced)
Bilirubin (high)
Liver membrane integrity tests
Alanine Aminotransferase (ALT)
Aspartate aminotransferase (AST)
*Can indicate the source of liver damage
High ALT/AST ratio indicates:
Characteristic for hepatic viral infection
High AST/ALT ratio
Characteristic for hepatic alcohol damage
Injury markers for obstructed bile ducts
1) Alkaline phosphatase (ALP)
2) gamma-glutamyl transferase (GGT)
Alkaline phosphatase (ALP)
Found in high concentration in cells of the bile canaliculi and biliary ducts. ALP cleaves phosphates from nucleotides and proteins which leads to alkaline pH of bile
Gamma-glutamyl transferase (GGT)
Bound to the plasma membrane of hepatocytes and is part of the hepatic gamma-glutamyl cycle for glutathione (GSH) synthesis
GGT increase in serum indicates:
Injury of bile ducts and of the liver. It can result from gallstones, ethanol or medical drugs.
Acute Pancreatitis due to:
-Heavy Alcohol intake
-Gallstone blockage
Chronic Pancreatitis due to:
Cystic Fibrosis (CF)
Hyperlipidemia
Years of ethanol abuse
Acute Pancreatitis is indicated by:
Increased serum levels of alpha-amylase and pancreatic lipase
Ethanol BASED Pancreatitis:
Serum lipase/amylase ratio grater than 2
Gallstone blockage marker
Increase of serum amylase, lipase, ALP, and GGT
A 56 year old male patient was admitted to the ER department with nausea, vomiting and epigastric abdominal pain. Upon examination and laboratory evaluation a provisional diagnosis of Acute Pancreatitis is concluded. In the condition of Acute Pancreatitis is Serum Lipase elevated: T/F
True
Alkaline Phosphatase
Found in bone, bile ducts, placenta, and intestine
*In bones: creates an alkaline pH for calcium deposition onto collagen
Prostate Cancer test
Prostate specific antigen test (instead of test for acid phosphatase)
Liver Cancer
Alpha-Fetoprotein (AFP): Protein is normally synthesized in the fetal liver (instead of albumin). In adults it can indicate liver cancer.
Features of Necrosis
*Pathological Process
1) Cell Swelling
2) Damage to Plasma membrane
3) Random DNA Degradation
Features of Apoptosis
*Physiological Process
1) Cell Shrinkage
2) Plasma Membrane Blebbing
3) Aggregation of Chromatin
4) Fragmentation of Nucleus
5) Oligonucleosomal DNA Fragmentation
Pathological Processes that lead to Necrosis
-Acute Cell Injury via:
1) Ischemia
2) Toxins
3) Infections
4) Trauma
5) Hypoxia
6) Radiation
Loss of plasma membrane integrity: cells swell: cellular contents are released (lysis)
Carcinoma
Malignant tumor growing from epithelial tissue
-Many carcinomas affect glands that are involved with secretion
Sarcoma
Malignant tumor growing from connective tissues
-Cartilage, fat, muscle, tendons. and bones
Ex. Osteosarcoma (bone) and chondrosarcoma (cartilage)
Leukemia
Cancer of the blood or bone marrow
Melanoma
Malignant tumor of melanocytes
Surface epithelium tumor
Benign: Papilloma/adenoma
Malignant: Carcinoma
Squamous Epithelial tumor
Benign: Squamous cell papilloma
Malignant: Squamous cell carcinoma
Glandular (columnar) epithelial tumor
Benign: Adenoma (villous or tubular)
Malignant: Adenocarcinoma
Transitional epithelial tumor
Benign: Transitional cell papilloma
Malignant: Transitional cell carcinoma
Solid Glandular epithelium Tumor
Benign: Adenoma
Malignant: Adenocarcinoma
Thyroid Tumor
Benign: Thyroid adenoma
Malignant: Thyroid Adenocarcinoma
Kidney Tumor
Benign: Renal Adenoma
Malignant: Renal Cell Carcinoma
Liver Tumor
Benign: Hepatic adenoma
Malignant: Hepatocellular carcinoma
Fibrous Tissue Tumor
Benign: Fibroma
Malignant: Fibrosarcoma
Bone Tumor
Benign: Osteoma
Malignant: Osteosarcoma
Cartilage Tumor
Benign: Chondroma
Malignant: Chondrosarcoma
Adipose Tissue Tumor
Benign: Lipoma
Malignant: Liposarcoma
Smooth muscle Tumor
Benign: Leiomyoma
Malignant: Leiomyosarcoma
Skeletal muscle Tumor
Benign: Rhabdomyoma
Malignant: Rhabomyosarcoma
Blood Vessel Tumor
Benign: Haemangioma
Malignant: Haemagiosarcoma
