Biochemistry

1. Biochemistry

2. Drug biotransformation: takes place in almost any tissue in the body, the most important being the liver. The most important site within the liver cells is the smooth endoplasmic reticulum. This is a thin tubular network inside the cell that participates in biotransformation. (When the liver is homogenized, the endoplasmic reticulum is broken up into microsomes). • In a competitive enzymatic reaction, the rate of the reaction is not affected by the addition of more substrate (E + S D ES – P). • Enzymes (apoproteins): these are protein in nature, used to catalyze biological reactions. • Ligase enzyme: rebuilds DNA which has been destroyed. • Amylase: is a pancreatic enzyme involved in the breakdown of starch. It is elevated in acute pancreatitis. • Chymopapin: is a proteolytic enzyme used to treat herniated lower back disks. • Pancrease: is most commonly used in patients suffering from: • Cystic fibrosis of pancreas. • Chronic pancreatitis. • Ligases: are one of the 6 main classes of enzymes. These enzymes catalyze the formation of bonds between 2 substrate molecules coupled with the hydrolysis of pyrophosphate bond in ATP or similar energy donor. • Protein Kinase: is activated by cyclic AMP (cAMP) & has regulatory subunits; its function is limited by some enzymes. • Phases of metabolism: there are 2 phases of metabolism • Phase I: Involves microsomal enzymes, catalyzed by cytochromes which may activate, inactivate or leave activity of drug unchanged. It includes metabolism by: aliphatic oxidation, sulfo-oxidation, N-oxidation, oxidative dealkylation, oxidative deamination, aromatic hydroxylation, N-dealkylation, S-demethylation, N-dehydroxylation, (Oxidation, reduction, hydroxylation, hydrolysis, deamination or demethylation). • Phase II: involves cytoplasmic & microsomal enzymes (separately or in combination) - deactivation of drugs by conjugation (with glucouronic acid, glycine or glutamine), acetylation, methylation or sulfation. • Mechanism of acetylation of the amino gp: is through Acetyl-Co-A + acetyl transferase • The typical cell contains the endoplasmic reticulum, responsible for the degradation of HB. • Cytochrome P 450: is associated with the extra-mitochondrial electron transfer in the liver, involved in “Mixed Function Oxidation” reaction in the liver & drug detoxication. It is an iron-protoprophyrin cellular pigment. • Cytoplasmic enzymes involved in biotransformation are oxidases (alcohol dehydrogenase), sulfatase, acyl transferase + mitochondrial enzymes (MAO & aldehyde dehydrogenase). • R–CH2–NH2 R–CO–NH2  R–CHO + NH3 (the reaction is oxidative deamination)

3. Plasma protein binding: If drug B has greater affinity (#er association constant) for a specific protein binding site than drug A. It will displace it. The larger the dose of drug B the greater the displacement (competitive reaction). • 50% of normal plasma protein is albumin. • Examples of pro-drugs include: Enalapril, L-dopa, Acetaminophen, Prednisone. • Hemoglobin: is made of 4 protein chain subunits (globulins), each chain containing one haem moiety. Haem consists of a tetra-pyrrole prophyrin ring containing Fe. Each haem can carry an oxygen molecule. • Sucrose (a disaccharide): upon hydrolysis  glucose + fructose. • Glucose & carbohydrate metabolism: • Under aerobic conditions (via Kreb’s cycle)  CO2 + H2O (end products) • Under anaerobic conditions (anaerobic glycolysis)  Lactic acid (end products) • Fat metabolism: the end products are CO2 & H2O. • Protein metabolism: proteins are polymers of amino acids • Metabolism of the nitrogen portion  Urea (end • Metabolism of the hydrocarbon portion  CO2 + H2O products) • In diabetic patients (insulin deficiency) protein is converted to glucose (gluconeogenesis)  weight loss. [Insulin inhibits gluconeogenesis] • Barbiturates ( & their analogues e.g. glutathemide) induce liver microsomal enzyme system & increase liver biotransformation. • When used chronically the dose of barbiturates should be increased (tolerance). • Phenobarbitone is used in the treatment of drug induced jaundice because it enhances glucoronide conjugation through induction of the microsomal enzyme system in the liver which enhances the production of bilirubin-binding Y protein. • Phenytoin induces the liver microsomal enzyme system  disturbs folic acid metabolism. • Disulfuram & Metronidazole: inhibit the metabolism of alcohol by inhibiting the alcohol dehydrogenase enzyme. Such drugs should not be given with alcohol because of the possibility of inducing disulfuram like reactions by inhibiting oxidation of acetaldehyde. • A substance that exists naturally in the body is called endogenous / endogenic. Drugs that induce liver microsomal enzymes Barbiturates Phenytoin Ethanol Nicotine Carbamazepine Rifampicine Drugs that inhibit liver microsomal enzymes Sulfa Erythromycin Quinolones Chloramphenicol Miconazole Cimetidine Allopurinol

4. Enkephalins: these are thought to be opiate-like peptides, localized in nerve endings. • Endorphins:b endorphin is the closest to morphine in action. • Histamine: stimulates gastric secretions. • Insulin: is the hormone that acts on the cell membrane. • Adjustment of the pH of body fluids: the immediate local adjustment of pH in body fluids is accomplished by buffers but the eventual disposition of acid (H+) is accomplished by lungs & kidney (i.e. the regulation of acidosis is 1st through the blood followed by lungs & kidney). • DNA contains 4 bases: (AGuThC) • Adenine & Guanine (purine bases) • Thionine & Cytosine (pyrimidine bases) • RNA contains 4 bases: (AGuUrC) (it contains uracil instead of thionine) • Adenine & Guanine (purine bases) • Uracil & Cytosine (pyrimidine bases) • The types of sugars in nucleic acids: • In RNA  Ribose • In DNA  Deoxyribose • N.B. Pyrimidine bases + Ribose  Nucleoside Nucleoside + Phosphoric acid  Nucleotides • Essential amino-acids: these are amino-acids that can not be synthesized in the body & must be taken with diet. They include: P H I L M V A L T T • Phenyl-alanine – Histadine – Isoleucine – Leucine • Methionine – Valine – Arginine – Lysine • Tryptophan – Threonine • Stearic acid: is a saturated fatty acid (18 carbons) with the formula CH3(CH2)16COOH. • Hemoglobin & cytochrome: are similar in the portion of prophyrin protein (heme protein) • The mitochondria (power house): contains all enzymes responsible for aerobic oxidation. • Transplantation rejection: is due to an immunity problem related to T cells (lymphocytes). • Mast cells can not be differentiated from basophiles. • At a pH below the iso-electric point (IEP), a protein will carry a +ve charge & will migrate to the – ve pole & vice versa. At a pH = IEP, it will ppt & will not migrate to either pole. • Creatinine phosphokinase enzyme: is responsible for ATP-creatinine trans-phosphorylase reaction. • Mast cells contain histamine & heparin.

5. OH N NO2 O • Any compound present normally in the body is called: • Metabolite c. Substrate • Exogenous substance d.Endogenous (endogenic) substance • Aromatic amines are metabolized through: • Hydroxylation c. Acetylation N.B. aliphatic amines by • Methylation oxidative deamination • Drugs that induce liver microsomal enzymes & increase its own metabolism are known to be associated with: • Carcinogenicity c. Tolerance • Dependence • The type of sugar in DNA is: • Ribose c. Desoxyribose • Arabinose • Gastric acid secretions are stimulated by: • Proteins. c.Fats (duodenum) • Carbohydrates  (Small intestine) • All enzymes are: • Proteins. c.Fats. N.B. coenzymes are vitamins • Carbohydrates. • What is DNA lygase used for: • For DNA replication • For DNA hydrolysis. • What enzyme or cofactor is involved in glycine conjugation: • Co-enzyme A or aryl transferase. (N-acetyl transferase / transacetylase) • Which is not related to lymphocytes (which is not part of the lymphatic system: • Spleen. • Thoracic duct. (The largest lymphatic vessel in the body.) • Thyroid e. Tonsils • Pancreas. f. Cisterna chyli • What type of metabolism does this compound undergo: • Oxidation. (OH gp) • Reduction. (NO2 gp) • Glucoronidation. ( –N – ) • Deamination. (Only 1ry amines undergo deamination)

6. CH2–CH– COOH HO NH2 HO • Aldosterone is secreted from: • Adrenal medulla b. Pituitary c. Adrenal cortex • When a pro-drug is converted inside the body to the active form, the phenomenon is called: • Bio-activation. b. Metabolism c. Bio-transformation. • Which of the following agents protect the integrity of the cell (protects the cell from damage): • Glutathione c. Cytochrome oxidase e. Methionine • Vitamin E d. Cytochrome P 450 • The compound shown [ (-) 3- (3,4 dihydroxyphenyl) – L – alanine)] is: • Epinephrine • A dextrorotatory compound • A precursor of dopamine (L-dopa) • Used to treat hypertension • An essential amino-acid • Which is found normally in DNA: • Cytosine. d. Ribose. • Uracil. e. Adenine. • Which is not found in DNA: • Uracil. b. Ribose • Which may give a false +ve test with 5 hydroxy indole acetic acid (5 HIAA) test: • NaCl d. Mephenesine • Glyceryl guaiacolate e. Ampicillin • Tetracycline • Which of the following enhances the activity of azathioprine (Imuran) by enzymatic oxidation inhibition: • Allopurinol d. Trimethoprim • Elase e. Tronyl cypromine • Dipyridamol • Prophyrin is involved in the building of: • Bone d. Blood Fe2+ prophyrin is the haem portion of HB • Muscle e. Scar tissue • Teeth • Which is the degradation process of desipramine: • Demethylation. b. Alkylation c. Hydrolysis

7. Sincalide (Kinevac) is used as a diagnostic aid to obtain a sample of: • Albumin d. Ketones • Gastric juice e.Bile (contracts gall bladder & evacuates it) • Blood sugar • The main carbohydrate of blood is: • D-fructose. c.D-glucose e. Sorbitol. • Mannitol d. L-glucose • Between particulate & miceller constituents in cells exists an aqueous phase which contains: • Soluble protein c. Cellular active products e. Electrolytes • Organic substance e.g. glucose d. All of the above • In the typical cell the mitochondria contains: • Cytochrome oxidase c. Cytochrome C e. All of the above • Succinic acid oxidase d. None of the above • The presence of mitochondria in the living cell can be detected by: • Neutral red. c. Phenolphthalein. e.Janvs green. • Methylene blue. d. None of the above. • The only disaccharide synthesized in human metabolism is: • Maltose c. Cellulose e.Fructose ???? • Lactose d. Erythrose • Conversion of b-carotene to vitamin A is carried out in: • Liver c. Thymus e. Spleen • Pancreas d. Adrenal cortex • The heat labile (thermolabile) factor in vitamin B complex is: • Riboflavin c. Folic acid e.Thiamine • Biotin d. Niacin • An enzyme acts a: • Catalyst b. Media • Which is not a microsomal (metabolic enzyme): • Cytochrome P 450 c. Cytochrome A • Cytochrome G d. Cytochrome 27 • What is the difference between extra-cellular & intra-cellular fluids: • Extra-cellular fluid contains more protein & Na+, intracellular fluid contains more K+

8. Which of the following is present in all connective tissue: • Mucoid d. All of the above • Lipids e. None of the above • Albuminoid (e.g. keratin present in hair & nails) • In the electrophoretic process, at a pH below the iso-electric point (7) a protein will: • Migrate to the +ve pole d. Form a zwitterion • Migrate to the -ve pole e. None of the above • Exhibit no migration • Colchicine can give a false +ve result for test of: • Glucose d. Ketones • Uric acid e. RBCs • Ureates • Keratin is a(n): • Protein d. Peptin • Albuminoid e. Ketone • Glutetin • Oxidation n humans is mediated by: • Ozones d. Glucoronidase • Amylases e. Co-enzyme A • Tryptophan • Butazol is used for clinical testing of: • Thyroid function d. Liver function • Gastric secretion e. Kidney function • Glucose tolerance • The average life of an RBC is about: • 7 days d. 1-2 months • 6 – 14 days e. 4 months (120 days) • 3 weeks • The metabolic degradation of Hb takes place in: • The reticulo-endothelial system d. Kidney tubules • RBCs e. All of the above • Liver cells • A reaction between an activated moiety & a transferase enzyme is: • Biotransformation (metabolism, degradation) b. Hydrolysis

9. The metabolic degradation of Hb leads to: • Formation of bile pigments d. Formation of biliuredine • Formation of urobilinogen e. All of the above • No oxidative cleavage of prophyrin ring • Lyophilization process is: • More effective than dialysis in protein solution purification. • Is generally not advisable for protein solutions. • Used for sterilization of some drugs by dehydration. • The non-protein portion of Hb consists of: • 3 haem units surrounding an iron atom. • 4 haem units surrounding a ferric ion. • A ferrous complex of protoprophyrin. • 4 pyrrole rings linked by a ferric molecule. • None of the above. • The amino-acid that is an important precursor of Hb is: • Alanine d. Leucine • Protine e. Histadine • Glycine • An important enzymatic reaction involved in muscular contraction is: • Glucose-6-phosphate d. Enolase • Glycogenolysis e. All of the above. • ATP-creatinine trans-phosphorylase reaction • Death due to cyanide poisoning results from: • Cyanide-Hb complex formation d. Coronary occlusion • Cyanide combining with RBCs e. None of the above • Cyanide inhibiting cytochrome-oxidase enzyme • Drugs containing hydroxyl (– OH) or a carboxyl (– COOH) gps are detoxicated by : • Hippuric acid d. Reduction • Acetylation e. Hydrolysis • Glucoronic acid (glycine or glutamine) • What is the difference between intracellular / extracellular fluids & plasma: • Plasma contains more proteins (albumin). • Plasma contains less proteins.

10. Nucleic acids DNA & RNA play an important role in the biosynthesis of protein. The sugar inherent to their structure is: • Glucose d. Sorbose • Sucrose e. None of the above • Fructose • Some tissues form lactic acid under anaerobic conditions. This phenomenon, specially characteristic of tumor tissue, is termed: • Anerobic glycolysis ( lactic a) • Oxidative phosphorylation ( ATP). • Lactation • Oxidation ( CO2 + H2O) • None of the above • Phenytoin causes elevated blood glucose level through: • Enhancing insulin degradation. d. Increasing glucose absorption. • Increasing glycogen release. e.Decreasing insulin release. • B & C. • R – NH2 + a -- b -- > R – NH – COCH3, What is “ a ” & “ b ” : • “ a ” is acetyl CoA & “ b ” is acetyl transferase. • Monocytes (aggranulocytes) resemble: • Neutrophils. c. Basophiles. • Eosinophils. d.Lymphocytes (both have no granular cytoplasm). • Enzyme action is in: • Golgi bodies. (secretory function) • Mitochondria. (power house) • Cytochrome. • Endoplasmic reticulum. • Metabolism is enhanced by: • Passive reabsorption. • What type of reaction is it when there is acetylation of sulphonamides at the amino gp: • It is a phase II reaction. • What is another name for metabolites present in the body: • Endogenic substances. • Which of the following is more in plasma than in interstitial fluid: • Proteins (Albumin). b. Na+. c. K+.

11. A person with blood group AB can receive blood from a person with blood group: • AB c. A e. O • A d. B • A woman with hemophelia & her husband has hemophelia which cannot be her daughter: • A girl without hemophelia • What does each of the following denote: • XX  Ban baby. • XXXY  Kleinfilter’s syndrome • OX  Turner’s syndrome • Sulphonamides are metabolized by: • Acetylation of the p-amino gp • Glucoronidation with glucoronic acid • Which is an essential amino acid: • Methionine. • Which of the following is responsible for nitrogen in NO in vivo: • L - arginine • Metabolism of sulphonamides takes place through: • Acetylation of the p-amino group & glucoronidation. • The end product of protein metabolism is: • Urea. • The end product of anerobic glycolysis is: • Lactic acid. • Which of the following is (are) phase II reactions: • Acetylation c. Glucoronidation • Deamination d. Hydroxylation • More of 50% of plasma proteins are: • Albumin • Phenobarbital may inhibit the effects of other drugs by: • Stimulating microsomal enzymes responsible for drug metabolism • Which of the following is functional gp metabolism: • Phase I b. Phase II • Phase I metabolism is called: • Functionalization

12. The thin tubular network in the cell that participates in biotransformation is: • The smooth endoplasmic reticulum • Which does not undergo biodegradation: • Poly-L-lactic acid b. Poly-D-lactic acid • What is the similarity between Hb & cytochrome P 450: • Both contain heme as prosthetic gp (heme portion) • Which of the following is a phase I biotransformation: • Sulfoxidation b. Acetylation • Which is present in the plasma in higher conc.: • CO2 b. HCO3 • Which is not secreted by the anteior pituitary: • ADH • ACTH is secreted by: • Pituitary gland. • Decreased ADH secretion leads to: • Increases Na reabsorption b. Thirst c. Polyuria • Which is present in RNA: • m-RNA (messanger) b. t-RNA (transfer) c. r-RNA (replicant) • Protein denaturation results from: • Agitation (shaking) b. Heating • Many hormones are sterilized by: • Radiation • To protect proteins, they are dried by: • Liophylization • Phosphorylation of phenytoin is by: ??? • Phosphorylase b. Esterase c. Amidase • Embolized cell enzymes are used to: • Prepare biological assay kits b. Preparation of drug metabolites • The 1ry structure of proteins is: • Special arrangement of sequenced amino acids • Aromatase enzyme is involved in the synthesis of: • Estrogens (e.g. estradiol) b. Histamine

13. What is Hb A 1c: • Glucosated Hb • Hydroxyl containing drugs are metabolized by: • Conjugation with glutathione • Which is not secreted from the anterior hypophesis: • ADH c. Prolactin e. ACTH • GH d. Adrenocortecoids f. Thyroxin • Which conjugate has a mercapto-purine linkage: • Glutathione b. Glycine c. Glutamine • Which accelerates the rate of metabolism of phenytoin: • Folic acid • The osmotic pressure of blood is: • 280 m osmole • Agranulocytosis is: • Type I hypersensitivity b. Type II hypersensitivity • Agranulocytosis is caused by all except: • Thiazides b. Sulpha c. Cimetidine • Which of the following stimulates the liver microsomal enzymes: • Alcohol d. Barbiturates f. Rifampicine • Nicotine e. Glutathemide g. Phenytoin • Cholestyramine ??? • In the shown reaction what type of metabolism is this: • Hydroxylation followed by glucoronidation • Organic acids are metabolized by: • Sulfation b. Conjugation c. Beta oxidation • Immunity is naturally present in the body because of: • T cells & B cells • DNA ligase is used for • Rebuild destroyed DNA b. DNA replication • Which is more accurate in measuring renal function: • CrCl b. SrCr

14. Which of the following enzymes is a metabolic enzyme: • Cytochrome P 450 b. Cytochrome G • Which is not involved in muscle contraction: • Inhibin c. Myotropin • Myosin d. Tropsonin • Which is not secreted from the anterior hypophesis: • ADH c. Prolactin e. ACTH • GH d. Adrenocortecoids f. Thyroxin • Which conjugate has a mercapto-purine linkage: • Glutathione b. Glycine c. Glutamine • Which accelerates the rate of metabolism of phenytoin: • Folic acid • The osmotic pressure of blood is: • 280 m osmole • Agranulocytosis is: • Type I hypersensitivity b. Type II hypersensitivity • Agranulocytosis is caused by all except: • Thiazides b. Sulpha c. Cimetidine • Which of the following stimulates the liver microsomal enzymes: • Alcohol d. Barbiturates f. Rifampicine • Nicotine e. Glutathemide g. Phenytoin • Cholestyramine ??? • In the shown reaction what type of metabolism is this: • Hydroxylation followed by glucoronidation • Organic acids are metabolized by: • Sulfation b. Conjugation c. Beta oxidation • Immunity is naturally present in the body because of: • T cells & B cells • DNA ligase is used for • Rebuild destroyed DNA b. DNA replication • Which is more accurate in measuring renal function: • CrCl b. SrCr