89. The blood clotting cascade in humans is represented in the picture below. Using this scheme answer the following questions:

a. Put correct coagulation factors and their active forms instead of the question marks in the picture;

b. Antithrombin is a glycoprotein produced by the liver and is responsible for inactivation of several enzymes of the coagulation system. Show the main targets of anthitrombin;

c. Blood clotting or coagulation is the body's major defense mechanism against blood loss. Such abnormalities as haemophilia A, B, C are the defects in the following clotting factors (show your answer in the picture using arrows);

d. Explain the role of protein C in blood coagulation.

Answer:

d. Several substances, known as anticoagulants, are in use to inhibit the blood clotting. The blood contains a potent anticoagulant namely protein C which is activated by thrombin. Active protein C hydrolyses and inactivates clotting factors V and VIII.

Section XIV Functional and clinical biochemistry of liver tissue. Biotransformation of xenobiotics and endogenous toxic compounds

1. Protoporphyrine cycle of heme is broken by the enzyme heme oxygenase with oxidation of one methene bridge, which is released as the next product:

1. Carbone monoxide

2. Formaldehyde

3. Carbone dioxide

4. Formic acid

5. Methane

2. Biliverdin is transformed into bilirubin by the next chemical process:

1. Reduction with involvement of NADPH

2. Oxidation with biliverdine oxidase

3. Hydroxylation by monooxygenase

4. Oxidative deamination

5. Decarboxylation of propionic acid residues

3. Daily urinary urobilinogen excretion in adult men is:

1. 0–4 mg

2. 5–8 mg

3. 9–12 mg

4. 13–20 mg

5. 25-45 mg

4. Bile pigments are not present in urine in:

1. Hepatic jaundice

2. Haemolytic jaundice

3. Obstructive jaundice

4. Rotor’s syndrome

5. Neonatal jaundice

5. Bilirubin UDP-glucuronyl transferase is absent from liver in:

1. Crigler-Najjar syndrome, type I

2. Gilbert’s disease

3. Crigler-Najjar syndrome, type II

4. Rotor’s syndrome

5. Dubin-Johnson syndrome

6. Lipoproteins of the next class are synthesized and released to blood as primary product by liver cells:

1. LDL

2. VLDL

3. IDL

4. HDL

5. Chylomicrons

7. In liver cholesterol is metabolized in all processes EXEPT:

1. Release to blood and thereafter excretion by kidneys

2. Biosynthesis of bile acids

3. Incorporation into plasma membranes of liver cells

4. Excretion as bile component

5. Incorporation into lipoprteins and trasport to peripheral tissues

8. An experimantal animal that was kept on protein-free diet developed fatty liver infiltration, in particular as a result of deficiency of methylating agents. This is caused by disturbed generation of the following metabolite:

A. Choline

B. DOPA

C. Cholesterol

D. Acetoacetate

E. Linoleic acid

9. Breakdown of 1gm hemoglobin produces:

1. 35 mg of bilirubin

2. 20 mg of bilirubin

3. 50 mg of bilirubin

4. 70 mg of bilirubin

5. 100 mg of bilirubin

10. Each hemoglobin molecule contains:

1. Four iron atoms

2. One iron atom

3. Two iron atoms

4. Three iron atoms

5. Six iron atoms

11. Fatty of phospholipids is disordered due to fat infiltration of the liver. Indicate which of the presented substances can enhance the process of methylation during phospholipids synthesis?

A. Methionine

B. Ascorbic acid

C. Glucose

D. Glycerin

E. Citrate

12. Free bilirubin (indirect bilirubin) is transformed in liver cells into conjugated (direct) bilirubin by conjugation with glucuronic acid with the aid of enzyme glucuronyl transferase. As substrate this enzyme uses the following compound:

1. UDP-glucuronate

2. Free glucuronate

3. CDP-glucose

4. CDP- glucuronate

5. UMP-glucuronate

13. In the normal resting state of human most of the blood glucose burnt as fuel is consumed by:

1. Liver

2. Brain

3. Adipose tissue

4. Muscles

5. Kidneys

14. What digestive process is altered in case of obstruction of bile duct and arrest of bile excretion to intestines?

1. Hydrolysis of triglycerides

2. Absorption of carbohydrates

3. Hydrolysis of proteins

4. Hydrolysis of complex sugars and polysaccharides

5. Absorption of amino acids.

15. During breakdown of hem, the methenyl bridge between the following two pyrrole rings is broken:

1. I and II

2. II and III

3. III and IV

4. IV and I

5. III and I

16. Pre- hepatic jaundice occurs because of:

1. Increased hemolysis

2. Liver damage

3. Biliary obstruction

4. Resus conflict

5. None of these

17. In dietary deficiency or insufficient production of endogeneous lipotropic factors in humans is developing fat degeneration of liver. What substances from listed below can be considered as lipotropic factor?

1. Choline

2. Fatty acids

3. Pyridoxine

4. Triacylglycerols

5. Cholesterol

18. Excretion of conjugated bilirubin from liver cells into biliary canaliculi is defective in:

1. Dubin-Johnson syndrome

2. Gilbert’s disease

3. Crigler-Najjar syndrome

4. Lucey-Driscoll syndrome

5. Rotor’s syndrome

19. To obese patient with risk of liver fat degeneration is recommended diet enriched with lipotropic factors. What nutritional component is the most important in diet?

1. Methionine

2. Cholesterol

3. Vitamin C

4. Glycine

5. Glucose

20. The greater amount of nitrogen is excreted from the organism in form of urea. Inhibition of urea synthesis and accumulation of ammonia in blood and tissues are induced by the decreased activity of the following liver enzyme:

A. Carbamoyl phosphate synthetase

B. Aspartate aminotransferase

C. Urease

D. Amylase

E. Pepsin

21. Reactions of methylation take place in biosynthesis of catecholamins, creatine, lecithin, as well as in detoxification of some xenobiotics. As donor of methyl groups serves the next substance:

A. Methionine

B. Leucine

C.Glutathion

D.Choline

E. Adenosine

22. Reduced NADP H₂ is necessary for biosynthesis of fatty acids, cholesterol, for detoxification of ammonia and xenobiotics. In what metabolic pathway is generated NADPH₂?

A. Hexosomonophosphate shunt

B.Oxidation of fatty acids

C. Gluconeogenesis

D. Glycolysis

E. Tricarboxylic acid (TCA) cycle

23. The process of microsomal oxidation has the next physiological significance:

A. Degradation of bile acids

B. Oxidative deamination of amino acids

C. Biosynthesis of steroid hormones

D. Utilization of unusual carbohydrates

E. Oxidation of fatty acids

24. Utilization and detoxification of ethanol in liver is performed by the next pathway:

1. Oxidation by dehydrogenases

2. Conjugation with glucuronic acid

3. Conjugation with sulfuric acid

4. Acetylation

5. Reduction with participance of glutathione

25. In oxidation of ethanol by microsomal oxidizing system besides acetaldehyde is generated the next additional harmful product:

1. Hydrogen peroxide

2. Superoxide anion

3. Hypochlorite anion

4. Malone dialdehyde

5. Carbone monoxide

26. Development of resistance toward drugs and medicinals (drug tolerance) appears due to the following process:

1. Increase in activity of microsomal oxidation

2. Decrease in activity of mitochomdrial oxidation

3. Increase in activity of mitochondrial oxidation

4. Decrease in activity of microsomal oxidation

5. Activation of peroxide oxidation

27. Monooxygenase systems of liver cell endoplasmic reticulum contain cytochrome P 450, NADPH₂ cytochrome P 450 reductase, FAD and FMN dependent enzymes. All these enzymes catalyze the following type of chemical reaction:

1. Hydroxylation

2. Acylation

3. Dehydrogenation

4. Methylation

5. Conjugation

28. What substance serves as donor of hydrogen in reactions of microsomal oxidation?

1. NADP H₂

2. Ascorbic acid

3. NAD H₂

4. FAD

5. FMN

29. Glucuronic acid which is used for conjugation reaction in detoxification of xenobiotics exists in the next active form:

1. UDP-glucuronate

2. Glucuronyl pyrophosphate

3. AMP-glucuronate

4. CDP-glucuronate

5. Glucuronyl-CoA

30. The aim of conjugation stage in detoxification of xenobiotics is as follows:

1. To make substance more soluble in water mrdium

2. To make substance fat soluble

3. To transform substance to insoluble form and deposit it in vesicles

4. To induce ingestion of substance by macrophages

31. Introduction of one oxygen atom into organic compounds is catalyzed by enzymes, which are defined as:

1. Peroxidases

2. Catalases

3. Dioxygenases

4. Monooxygenases

5. Oxidases

32. Harmful effect of alkaloid cocaine on liver cells is caused by its bioactivation and formation of nitroxide derivative, which is a strong oxidant. The transformation is initiated by the following chemical reaction:

A. N-dealkylation

B. Deacylation

C. O-dealkylation

D. Hydrolysis

E. N-hydroxylation

33. Besides cytochrome P-450 microsomal oxidation system in liver cell exists the second monooxygenase system, which is provided by the next enzyme:

1. Glutathion peroxidase

2. Catalase

3. FAD containing oxygenase

4. Monoamine oxidase

5. Xanthine oxidase

34. Sulfate is used in conjugation step of detoxification as the following active form:

A. Phosphoadenosyl phosphosulfate

B. UDP-sulfate

C. Sulfuryl-CoA

D. Guanosine sulfate

5. Thionyl chloride

35. Detoxification function of liver in patients is evaluated with the following test:

1. Quick test (hippuric acid synthesis)

2. Glucose tolerance test

3. Bilirubin concentration in blood

4. LDL content in blood serum

36. During the investigation of detoxification function of liver a patient was given 4 g of sodium benzoate per os. From urine, collected during four subsequent hours, it was obtained 1 g of hippuric acid. What indicates this result?

A.Normal value of detoxification function of liver

В. Insufficient detoxification function of liver

C. Enhanced detoxification function of liver

37. What coenzyme is necessary for NADPH-cytochrome P450 reductase activity?

1. NADP

2. ATP

3. FAD

4. FMN

5. FAD and FMN both

38.Cytochrome P450 belongs to the next class of enzymes:

A.Oxidoreductases

B. Transferases

C. Hydrolases

D. Lyases

E. Isomerases

39. Flavin containing monooxygenase belongs to the next class of enzymes:

A. Oxidoreductases

B. Transferases

C. Hydrolases

D. Lyases

E. Isomerases

40. Chose the correct statement about characteristic properties of flavin containing monooxygenase of liver tissue.

A. This enzyme exhibits a narrow stereochemical substrate specificity

B. Its activity is modulated by calmodulin

C. It is constitutive enzyme, activity not dependent from presence of inducers.

D. It forms a hydroperoxide derivative of FAD (peroxyflavin) which oxidizes substrate

E. It generates hydrogen peroxide, which oxidizes substrate