L.4 Protein Digestion/Urea Cycle Diseases

Question 1

Cystic Fibrosis

Answer 1

-Dried secretions block pancreatic duct -> Loss of digestive proteins -> malabsorption -> malnutrition ->poor growth in children/ low serum protein (albumin) levels
Tx: Pancreatic enzyme supplement

Question 2

Chronic Pancreatitis

Answer 2

-Loss of enzyme secreting pancreatic cells-> Loss of digestive proteins -> malabsorption -> malnutrition ->poor growth in children/ low serum protein (albumin) levels
Tx: Pancreatic -enzyme supplement

Question 3

Cystinuria

Answer 3

• AA absorption disorder
• Don’t absorb Cystine, Ornithine, Arginine, Lysine, they accumulate in intestines/kidney and are expelled in urine
• High cystine levels can cause cystine stones

Question 4

Type I Hyperammonemia

Answer 4

• CPSI or N-acetylglutamate Synthase deficiency

- Normal Orotic acid in urine

Question 5

Type II Hyperammonemia

Answer 5

• Ornithine Transcarbomoylase deficienyc
• High Orotic Acid in urine
• Low citrulline levels

Question 6

Citrullinuria

Answer 6

• Argininosuccinate Synthetase deficiency
• High Citrulline
• Low Arginosuccinate

Question 7

Argininosuccinic Acidemia

Answer 7

• Arginosuccinate Lyase
• High Arginosuccinate
• Low Arginine

Question 8

Arginemia

Answer 8

• Arginase deficiency
• High arginine
• Low Urea/ornnithine

Question 9

Alanine Aminotrasnferase (ALT)

Answer 9

• Alanine Glutamate
• B6/PLP
• Transfers AA NH3 to Glutamate for nitrogen removal in AA degradation
• Glucose/Alanine Cycle
• High serum level = liver damage

Question 10

Aspartate Aminotransferase (AST)

Answer 10

• Aspartate Glutamate
• B6/PLP
• Transfers AA NH3 to Glutamate for nitrogen removal in AA degradation
• High serum level = liver damage

Question 11

Glutamate Dehydrogenase (GDH)

Answer 11

• Removal of NH3 from Glutamate for urea cycle (oxidative deamination, needs NAD)
• Glutamate + NAD–> a-Ketoglutarate + NH3
• Fixation of free NH3 to Glutamate for AA synthesis, controls ammonia concentration (reductive amination, need NADPH)
• a-Ketoglutarate + NH3 + NADPH –> Glutarate

Question 12

Transaminases/ Aminotransferases

Answer 12

• Transfer nitrogen from AA to a-Ketoglutarate
• Collect nitrogen to avoid release of free ammonia
• Transfer ammonia from Glutamate to Alanine and Glutamine for NH3 transport to liver for urea cycle

Question 13

Glutamine Synthase

Answer 13

• Fixes free ammonia to Glutamine
• Glutamate + ATP + NH4+ –> Glutamine
• Main detoxifaction in brain

Question 14

Carbamoyl Phosphate Synthetase I

Answer 14

• Fixes free ammonia to Carbamoyl Phosphate
• CO2 + 2 ATP + NH4+ –> Carbamoyl Phosphate
• 1st step in Urea Cycle

Question 15

Scavenger Drugs

Answer 15

• Used to treat hereditary hyperammonemias
• Benzoic acid/phenylbutarate
• Conjugate glycine/glutamine and target them for urinary excretion
• Also cause body to use NH3 to produce them

Question 16

Urea Cycle

Answer 16

Mitochondria
1. CO2 +NH3 + 2ATP –Carbamoyl Phosphate Synthetase I +N-Acetylglutamate –> Carbamoyl Phosphate –>
2. Ornithine Transcarbomyalase –> Citrulline –>
Cytosol
3. Arginosuccinate Synthetase –> Arginosuccinate –>
4. Arginosuccinate Lyase –> Arginine –>
5. Arginase –> Ornithine/ Urea