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Lesson 19. DETOXIFICATION OF AMMONIA. AMINO ACID CATABOLISM. METABOLISM OF HEMOPROTEINS AND NUCLEOPROTEINS

Questions to study.

1. Toxicity of ammonia. Pathways of ammonia detoxification. Urea cycle.

2. Genetic anomalies of enzymes of the urea cycle.

3. Creatine and creatine phosphate biosynthesis. Significance of creatine phosphate. Metabolism of creatine.

4. Heme synthesis. Genetic defects enzymes of heme synthesis.

5. Heme catabolism. Disorders of heme catabolism. Jaundice.

6. Biosynthesis of purine nucleotides: origin of purine rings atoms, initial stages of biosynthesis (from rybose-5-phosphate to 5-phosphorybosilamine). Salvage pathways of purine nucleotide synthesis. Regulation of biosynthesis. Purine nucleotide decomposition. Hyperuricemia and gout.

7. Biosynthesis and decomposition of pyrimidine nucleotides. Salvage pathways of pyrimidine nucleotide synthesis. Regulation of pyrimidine nucleotide biosynthesis. Orotate and methyluracil as non-specific anabolics.

Assignment for self-instruction

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Task

Guidelines for performing the task

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3

1

Study the ways of detoxification of ammonia in the body

1. Write down reactions of glutamine synthesis and degradation.

2. Describe modern views on toxicitity of ammonia. Write down the scheme of ammonia excretion with urine.

3. Make a schematic drawing of relationship between ornithine cycle and citric acid cycle.

Continued of the table

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4. Explain which compounds are donors of the first and second nitrogen atoms in urea molecule. Write down reactions of ornithine cycle where these compounds are utilized

2

Study metabolism of certain amino acids (arginine, glycine, metionine)

1. Write down reacions of synthesis of creatine, creatine phosphate and creatinine.

2. Indicate the role of creatine phosphate.

3. Describe metabolism of creatine and its significance

3

Consider metabolism of iron in human body

1. Write down the daily requirement values for iron, depending on age and sex.

2. Make a schematic drawing of iron transport starting from absorption in the intestine until its utilization using in tissues for metabolic needs.

3. Explain the biological function of ferritin, transferrin, haptoglobin, hemosiderin

4

Study metabolism of hemoglobin

1. Write down the reactions of hemoglobin synthesis. Indicate the rate-limiting enzymes.

2. Pay attention to the feature of iron incorporation in the protopor-phyrin ring.

3. Explain why deficiency of vitamins B2, folic acid, B12, microelements (Fe, Co) leads to development of anemia.

4. Write down a scheme of of hemoglobin breakdown and formation of bile acids.

5. Write down the reaction of enzymatic conversion of indirect biliru-bin to direct one in hepatocytes.

6. List the main types of jaundice. Explain the difference in the metabolism of bile pigments at various types of jaundice.

7. Explain the causes and mechanism of development of jaundice in newborns.

8. Explain the diagnostic significance of bilirubin and other bile pigments assay in the blood and urine

5

Study tissue synthesis of mononucleo-tides

1. Indicate the origin of purine ring atoms.

2. Describe the role of folic acid and vitamin B12 in the synthesis of purine nucleotides and deoxyribonucleotides.

3. Write down salvage pathways of mononucleotide synthesis.

4. Write down reactions of orotic acid synthesis.

5. Describe the mechanism of mononucleotide biosynthesis

6

Consider the mechanism of tissue breakdown of pyrimidine mononucleotides

1. Name the main end products of pyrimidine mononucleotide catabolism

Ending of the table

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7

Study catabolism of purine nucleotides

1. Write down chemical reactions of adenylic acid catabolism to uric acid.

2. make a schematic representation of the sequence of guanylic acid degradation.

3. Consider the causes of hyperuricemia in gout

Library-research paper 1. Porphyria.

LABORATORY WORK

1. Quantification of creatinine in the blood serum

Creatinine is one of the end products of amino acid metabolism:

Quantitative determination of creatinine is based on its property to react with picric acid in alkaline medium with formation of a colored product. Intensity of the emerging color is proportional to the concentration of creatinine in the sample.

Procedure

► Mark six centrifuge tubes as 1-6.

► Pipette 0.5 ml of blood serum, 1.0 ml of distilled water and 0.5 ml of 10% thrichloroacetic acid (TCA) solution into tube 1. Stir intensively with a glass rod (experimental sample).

► Pipette 1.0 ml of distilled water, 0.5 ml of standard solution of creatinine and 0.5 ml of TCA solution into tube 2. Stir intensively with a glass rod (standard sample).

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