19 Biochemistry

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Biochemistry

• 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  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)
• 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.

Drugs that induce liver microsomal enzymes Drugs that inhibit liver microsomal enzymes

Barbiturates Phenytoin Sulfa Erythromycin


Ethanol Nicotine Quinolones Chloramphenicol
Carbamazepine Rifampicine Miconazole Cimetidine
Allopurinol
• A substance that exists naturally in the body is called endogenous / endogenic.
• Enkephalins: these are thought to be opiate-like peptides, localized in nerve endings.
• Endorphins:  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 1 st 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 CH 3(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.
1. Any compound present normally in the body is called:
a. Metabolite c. Substrate
b. Exogenous substance d. Endogenous (endogenic) substance
2. Aromatic amines are metabolized through:
a. Hydroxylation c. Acetylation N.B. aliphatic amines by
b. Methylation oxidative deamination
3. Drugs that induce liver microsomal enzymes & increase its own metabolism are known to be
associated with:
a. Carcinogenicity c. Tolerance
b. Dependence
4. The type of sugar in DNA is:
a. Ribose c. Desoxyribose
b. Arabinose
5. Gastric acid secretions are stimulated by:
a. Proteins. c. Fats  (duodenum)
b. Carbohydrates  (Small intestine)
6. All enzymes are:
1. Proteins. c. Fats. N.B. coenzymes are vitamins
a. Carbohydrates.
a. What is DNA lygase used for:
1. For DNA replication
a. For DNA hydrolysis.
b. What enzyme or cofactor is involved in glycine conjugation:
1. Co-enzyme A or aryl transferase. (N-acetyl transferase / transacetylase)
c. Which is not related to lymphocytes (which is not part of the lymphatic system:
a. Spleen.
b. Thoracic duct. (The largest lymphatic vessel in the body.)
c. Thyroid e. Tonsils
1. Pancreas. f. Cisterna chyli
d. What type of metabolism does this compound undergo:
a. Oxidation. (OH gp) OH
b. Reduction. (NO2 gp)
NO2 N
c. Glucoronidation. ( –N – )
d. Deamination. (Only 1ry amines undergo deamination) O
11. Aldosterone is secreted from:
a. Adrenal medulla b. Pituitary c. Adrenal
cortex
12. When a pro-drug is converted inside the body to the active form, the phenomenon is called:
a. Bio-activation. b. Metabolism c. Bio-transformation.
13. Which of the following agents protect the integrity of the cell (protects the cell from damage):
a. Glutathione c. Cytochrome oxidase e. Methionine
b. Vitamin E d. Cytochrome P 450
14. The compound shown [ (-) 3- (3,4 dihydroxyphenyl) – L – alanine)] is:
a. Epinephrine
b. A dextrorotatory compound HO CH2–CH – COOH
c. A precursor of dopamine (L-dopa)
HO NH2
d. Used to treat hypertension
e. An essential amino-acid
15. Which is found normally in DNA:
a. Cytosine. d. Ribose.
b. Uracil. e. Adenine.
16. Which is not found in DNA:
a. Uracil. b. Ribose
17. Which may give a false +ve test with 5 hydroxy indole acetic acid (5 HIAA) test:
11. NaCl d. Mephenesine
12. Glyceryl guaiacolate e. Ampicillin
a. Tetracycline
18. Which of the following enhances the activity of azathioprine (Imuran) by enzymatic oxidation
inhibition:
a. Allopurinol d. Trimethoprim
b. Elase e. Tronyl cypromine
11. Dipyridamol
a. Prophyrin is involved in the building of:
a. Bone d. Blood Fe2+ prophyrin is the haem portion
of HB
b. Muscle e. Scar tissue
c. Teeth
11. Which is the degradation process of desipramine:
a. Demethylation. b. Alkylation c. Hydrolysis
21. Sincalide (Kinevac) is used as a diagnostic aid to obtain a sample of:
a. Albumin d. Ketones
b. Gastric juice e. Bile (contracts gall bladder & evacuates it)
c. Blood sugar
22. The main carbohydrate of blood is:
a. D-fructose. c. D-glucose e. Sorbitol.
b. Mannitol d. L-glucose
23. Between particulate & miceller constituents in cells exists an aqueous phase which contains:
a. Soluble protein c. Cellular active products e.
Electrolytes
b. Organic substance e.g. glucose d. All of the above
24. In the typical cell the mitochondria contains:
a. Cytochrome oxidase c. Cytochrome C e. All of the above
b. Succinic acid oxidase d. None of the above
25. The presence of mitochondria in the living cell can be detected by:
a. Neutral red. c. Phenolphthalein. e. Janvs green.
b. Methylene blue. d. None of the above.
26. The only disaccharide synthesized in human metabolism is:
21. Maltose c. Cellulose e. Fructose ????
a. Lactose d. Erythrose
a. Conversion of -carotene to vitamin A is carried out in:
21. Liver c. Thymus e. Spleen
a. Pancreas d. Adrenal cortex
b. The heat labile (thermolabile) factor in vitamin B complex is:
21. Riboflavin c. Folic acid e. Thiamine
a. Biotin d. Niacin
c. An enzyme acts a:
21. Catalyst b. Media
d. Which is not a microsomal (metabolic enzyme):
a. Cytochrome P 450 c. Cytochrome A
21. Cytochrome G d. Cytochrome 27
e. What is the difference between extra-cellular & intra-cellular fluids:
a. Extra-cellular fluid contains more protein & Na +, intracellular fluid contains more
K+
32. Which of the following is present in all connective tissue:
a. Mucoid d. All of the above
b. Lipids e. None of the above
c. Albuminoid (e.g. keratin present in hair & nails)
33. In the electrophoretic process, at a pH below the iso-electric point (7) a protein will:
a. Migrate to the +ve pole d. Form a zwitterion
b. Migrate to the -ve pole e. None of the above
c. Exhibit no migration
34. Colchicine can give a false +ve result for test of:
a. Glucose d. Ketones
b. Uric acid e. RBCs
c. Ureates
35. Keratin is a(n):
a. Protein d. Peptin
b. Albuminoid e. Ketone
c. Glutetin
36. Oxidation n humans is mediated by:
a. Ozones d. Glucoronidase
b. Amylases e. Co-enzyme A
c. Tryptophan
37. Butazol is used for clinical testing of:
32. Thyroid function d. Liver function
33. Gastric secretion e. Kidney function
a. Glucose tolerance
a. The average life of an RBC is about:
32. 7 days d. 1-2 months
33. 6 – 14 days e. 4 months (120 days)
a. 3 weeks
b. The metabolic degradation of Hb takes place in:
32. The reticulo-endothelial system d. Kidney tubules
33. RBCs e. All of the above
34. Liver cells
c. A reaction between an activated moiety & a transferase enzyme is:
a. Biotransformation (metabolism, degradation) b. Hydrolysis
41. The metabolic degradation of Hb leads to:
a. Formation of bile pigments d. Formation of biliuredine
b. Formation of urobilinogen e. All of the above
c. No oxidative cleavage of prophyrin ring
42. Lyophilization process is:
a. More effective than dialysis in protein solution purification.
b. Is generally not advisable for protein solutions.
c. Used for sterilization of some drugs by dehydration.
43. The non-protein portion of Hb consists of:
a. 3 haem units surrounding an iron atom.
b. 4 haem units surrounding a ferric ion.
c. A ferrous complex of protoprophyrin.
d. 4 pyrrole rings linked by a ferric molecule.
e. None of the above.
44. The amino-acid that is an important precursor of Hb is:
a. Alanine d. Leucine
b. Protine e. Histadine
c. Glycine
45. An important enzymatic reaction involved in muscular contraction is:
a. Glucose-6-phosphate d. Enolase
b. Glycogenolysis e. All of the above.
c. ATP-creatinine trans-phosphorylase reaction
46. Death due to cyanide poisoning results from:
41. Cyanide-Hb complex formation d. Coronary occlusion
42. Cyanide combining with RBCs e. None of the above
a. Cyanide inhibiting cytochrome-oxidase enzyme
a. Drugs containing hydroxyl (– OH) or a carboxyl (– COOH) gps are detoxicated by :
41. Hippuric acid d. Reduction
42. Acetylation e. Hydrolysis
a. Glucoronic acid (glycine or glutamine)
b. What is the difference between intracellular / extracellular fluids & plasma:
41. Plasma contains more proteins (albumin).
42. Plasma contains less proteins.
49. Nucleic acids DNA & RNA play an important role in the biosynthesis of protein. The sugar
inherent to their structure is:
a. Glucose d. Sorbose
b. Sucrose e. None of the above
c. Fructose
50. Some tissues form lactic acid under anaerobic conditions. This phenomenon, specially
characteristic of tumor tissue, is termed:
a. Anerobic glycolysis ( lactic a)
b. Oxidative phosphorylation ( ATP).
c. Lactation
d. Oxidation ( CO2 + H2O)
e. None of the above
51. Phenytoin causes elevated blood glucose level through:
a. Enhancing insulin degradation. d. Increasing glucose absorption.
b. Increasing glycogen release. e. Decreasing insulin release.
c. B & C.
52. R – NH2 + a -- b -- > R – NH – COCH3, What is “ a ” & “ b ” :
a. “ a ” is acetyl CoA & “ b ” is acetyl transferase.
53. Monocytes (aggranulocytes) resemble:
a. Neutrophils. c. Basophiles.
b. Eosinophils. d. Lymphocytes (both have no granular cytoplasm).
54. Enzyme action is in:
a. Golgi bodies. (secretory function)
b. Mitochondria. (power house)
c. Cytochrome.
d. Endoplasmic reticulum.
55. Metabolism is enhanced by:
a. Passive reabsorption.
a. What type of reaction is it when there is acetylation of sulphonamides at the amino gp:
49. It is a phase II reaction.
b. What is another name for metabolites present in the body:
a. Endogenic substances.
49. Which of the following is more in plasma than in interstitial fluid:
a. Proteins (Albumin). b. Na+. c. K+.
59. A person with blood group AB can receive blood from a person with blood group:
a. AB c. A e. O
b. A d. B
60. A woman with hemophelia & her husband has hemophelia which cannot be her daughter:
a. A girl without hemophelia
61. What does each of the following denote:
a. XX  Ban baby.
b. XXXY  Kleinfilter’s syndrome
c. OX  Turner’s syndrome
62. Sulphonamides are metabolized by:
a. Acetylation of the p-amino gp
b. Glucoronidation with glucoronic acid
63. Which is an essential amino acid:
a. Methionine.
64. Which of the following is responsible for nitrogen in NO in vivo:
a. L - arginine
65. Metabolism of sulphonamides takes place through:
59. Acetylation of the p-amino group & glucoronidation.
a. The end product of protein metabolism is:
a. Urea.
59. The end product of anerobic glycolysis is:
a. Lactic acid.
60. Which of the following is (are) phase II reactions:
a. Acetylation c. Glucoronidation
b. Deamination d. Hydroxylation
61. More of 50% of plasma proteins are:
a. Albumin
a. Phenobarbital may inhibit the effects of other drugs by:
59. Stimulating microsomal enzymes responsible for drug metabolism
b. Which of the following is functional gp metabolism:
59. Phase I b. Phase II
c. Phase I metabolism is called:
59. Functionalization
73. The thin tubular network in the cell that participates in biotransformation is:
a. The smooth endoplasmic reticulum
74. Which does not undergo biodegradation:
a. Poly-L-lactic acid b. Poly-D-lactic acid
75. What is the similarity between Hb & cytochrome P 450:
a. Both contain heme as prosthetic gp (heme portion)
76. Which of the following is a phase I biotransformation:
a. Sulfoxidation b. Acetylation
77. Which is present in the plasma in higher conc.:
a. CO2 b. HCO3

78. Which is not secreted by the anteior pituitary:


a. ADH
79. ACTH is secreted by:
a. Pituitary gland.
80. Decreased ADH secretion leads to:
a. Increases Na reabsorption b. Thirst c. Polyuria
81. Which is present in RNA:
a. m-RNA (messanger) b. t-RNA (transfer) c. r-RNA (replicant)
82. Protein denaturation results from:
a. Agitation (shaking) b. Heating
83. Many hormones are sterilized by:
a. Radiation
84. To protect proteins, they are dried by:
a. Liophylization
85. Phosphorylation of phenytoin is by: ???
a. Phosphorylase b. Esterase c. Amidase
86. Embolized cell enzymes are used to:
a. Prepare biological assay kits b. Preparation of drug metabolites
87. The 1ry structure of proteins is:
a. Special arrangement of sequenced amino acids
88. Aromatase enzyme is involved in the synthesis of:
a. Estrogens (e.g. estradiol) b. Histamine
89. What is Hb A 1c:
a. Glucosated Hb
90. Hydroxyl containing drugs are metabolized by:
a. Conjugation with glutathione
91. Which is not secreted from the anterior hypophesis:
a. ADH c. Prolactin e. ACTH
b. GH d. Adrenocortecoids f. Thyroxin
92. Which conjugate has a mercapto-purine linkage:
a. Glutathione b. Glycine c. Glutamine
93. Which accelerates the rate of metabolism of phenytoin:
a. Folic acid
94. The osmotic pressure of blood is:
a. 280 m osmole
95. Agranulocytosis is:
a. Type I hypersensitivity b. Type II hypersensitivity
96. Agranulocytosis is caused by all except:
a. Thiazides b. Sulpha c. Cimetidine
97. Which of the following stimulates the liver microsomal enzymes:
a. Alcohol d. Barbiturates f. Rifampicine
b. Nicotine e. Glutathemide g. Phenytoin
89. Cholestyramine ???
a. In the shown reaction what type of metabolism is this:

a. Hydroxylation followed by glucoronidation


89. Organic acids are metabolized by:
a. Sulfation b. Conjugation c. Beta oxidation
90. Immunity is naturally present in the body because of:
a. T cells & B cells
91. DNA ligase is used for
a. Rebuild destroyed DNA b. DNA replication
92. Which is more accurate in measuring renal function:
a. CrCl b. SrCr
103. Which of the following enzymes is a metabolic enzyme:
a. Cytochrome P 450 b. Cytochrome G
104. Which is not involved in muscle contraction:
a. Inhibin c. Myotropin
b. Myosin d. Tropsonin

105. Which is not secreted from the anterior hypophesis:


a. ADH c. Prolactin e. ACTH
b. GH d. Adrenocortecoids f. Thyroxin
106. Which conjugate has a mercapto-purine linkage:
a. Glutathione b. Glycine c. Glutamine
107. Which accelerates the rate of metabolism of phenytoin:
a. Folic acid
108. The osmotic pressure of blood is:
a. 280 m osmole
109. Agranulocytosis is:
a. Type I hypersensitivity b. Type II hypersensitivity
110. Agranulocytosis is caused by all except:
a. Thiazides b. Sulpha c. Cimetidine
111. Which of the following stimulates the liver microsomal enzymes:
a. Alcohol d. Barbiturates f. Rifampicine
b. Nicotine e. Glutathemide g. Phenytoin
103.Cholestyramine ???
a. In the shown reaction what type of metabolism is this:

a. Hydroxylation followed by glucoronidation


103. Organic acids are metabolized by:
a. Sulfation b. Conjugation c. Beta oxidation
104. Immunity is naturally present in the body because of:
a. T cells & B cells
105. DNA ligase is used for
a. Rebuild destroyed DNA b. DNA replication
106. Which is more accurate in measuring renal function:
a. CrCl b. SrCr

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