Clinical cases and Situational tasks
134. Amital is pharmaceutical, which is used in pharmacology as a hypnotic agent. What is the mechanism of its actions on the processes of tissue respiration?
Answer: Amital (aminobarbital) – a derivative of barbituric acid, which inhibits cellular respiration by blocking electron transport ,at the level provided with the-coenzyme Q-reductase.
135. A patient with overactivity of the thyroid gland. Why biological oxidation in cells is disturbed?
Answer: Thyroid hormones (thyroxine, triiodothyronine) activate Na+, K+-ATP-ase. With their action, they observed the active absorption of O2 mitochondria without a corresponding increase in the synthesis of ATP.
136. The patient, who had been using phenobarbital to treat Gilbert’s disease, developed addiction to this drug. How can you explain the mechanism of this addiction?
Answer: The addiction to phenobarbital induction explained by the synthesis of cytochrome P-450. The phenobarbital oxidized mono-oxygenase system of endoplasmic reticulum with cytochrome P-450.
137. Why do patients with cardiovascular failure and signs of acidosis to administered the cocarboxilase (thiamine pirophosphate) drug?
Answer: Cocarboxilase (thiamine pirophosphate) is coenzyme form of vitamin B1, which is a part of enzymes involved in oxidative dekabooxydation α-ketoacids (eg pyruvate dehydrogenase). Cocarboxilase prescribed for acidosis origin of diabetes, hepatic and renal failure, respiratory acidosis, chronic pulmonary heart failure and coronary insufficiency and a number of different processes that improve energy metabolism.
138. A postoperative patient on intravenous fluids develops lesions in the mouth (angular stomatitis). Urinalysis indicates an excretion of 15 μg riboflavin/mg creatinine, which is abnormally low. Which of the following TCA cycle enzymes is most likely to be affected?
Answer: The patient has demonstrated a deficiency in riboflavin (urinary excretion of less than 30 μg/mg creatinine is considered clinically deficient). Riboflavin is a component of the cofactor FAD (flavin adenine dinucleotide), which is required for the conversion of succinate to fumarate by succinate dehydrogenase.
139. After excessive drinking over an extended period of time while eating poorly, a middle-aged man is admitted to the hospital with “high output” heart failure. Which of the following enzymes is most likely inhibited?
Answer: This patient has exhibited symptoms of beri beri heart disease, which is a result of a nutritional deficiency in vitamin B1 (thiamine). The active form of the vitamin, thiamine pyrophosphate, is a required cofactor for α-ketoglutarate dehydrogenase.
140. ATP may be hydrolysed to form ADP and Pi (orthophosphate) or AMP and PPi (pyrophosphate). Pyrophosphate may be subsequently hydrolyzed to orthophosphate releasing additional free energy. Note the ΔGo values (1, 2 and 3), which are released in each reaction.
Answer: 1 - DGo=-7.3 kcal (-30.5 kJ/mol), 2 - DGo'=-7.7 kcal (-32.2 kJ/mol), 3 - DGo'=-8 kcal (-33.5 kJ/mol)
141. A 16-month-old girl was found to have ingested approimately 30 mL of an acetonitrile-based cosmetic nail remover when she vomited 15 minutes postingestion. The poison control center was contacted, but no treatment was recommended because it was confused with an acetone-based nail polish remover. The child was put to bed at her normal time, which was 2 hours postingestion. Respiratory distress developed sometime after the child was put to bed, and she was found dead the next morning. Inhibition of which of the following enzymes was the most likely cause of this child’s death?
Answer: The culprit here is cyanide produced from acetonitrile. Cyanide inhibits the electron transport chain of cytochrome oxidase.
142. Several molecules are known to specifically inhibit the electron transport process. Used in conjunction with reduction potential measurements, inhibitors have been invaluable in the determination of the correct order of electron-transport chain components. Insert the corresponding inhibitors (at the scheme) to the sites of their action.
Answer: 1- rotenone (a plant toxin used by Amazonian Indians to poison fish and is also used as an insecticide), amital (a barbiturate); 2- Antimicin A, 3- monoxide (CO), azide (N3-) and cyanide
143. Name the respiratory inhibitors, shown below:
Answer:1 – rotenone, 2 – amytal, 3 – cyanide, 4 – antymycin A.
144. Explain the role of ATP-synthase components, shown below:
Answer: The F1 headpiece includes three α and three β subunits one copy each of three other subunits (γ, δ and ε. F0 includes a cluster of 9-12 copies of a small peptide, which appears to form a transmembrane channel for protons.
145. Name enzymes of citric acid cycle:
Answer:1 – Citrate synthase, 2, 3 – aconitase, 4, 5 – isocitrate dehydrogenase, 6 – a-ketoglutarate dehydrogenase complex, 7 – succinate thiokinase, 8 – succinate dehydrogenase, 9 – fumarase, 10 - malate dehydrogenase.
146. Fill in the blanks:
a
b
c
Answer: a – acetyl CoA, citrate syntase; b – isocitrate dehydrogenase, CO2 ; c – malat dehydrogenase
147. Inhibition of oxidative phosphorylation by cyanide ion leads to increases in which of processes?
Answer: Gluconeogenesis requires ATP, which is in short supply, turning up the catabolism of glucose to lactate in the absence of an intact electron transport chain. ADP cannot be transported into the mitochondrion because ATP, its antiporter partner, isn’t made by oxidative phosphorylation as a result of cyanide inhibition of cytochrome oxidase. Metabolism of fatty acids and ketone bodies requires a functional electron transport chain for their metabolism, and these possibilities are also ruled out.
148. Name the following compounds of Krebs cycle:
Answer: 1 – oxaloacetate, 2 – malate, 3 – fumarate, 4 – citrate