Urea Cycle and Protein Digestion

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Urea Cycle

• Amino acids are added or removed for nitrogen balance.
• Protein digestion involves pepsinogen, pepsin, zymogen, cholecystokinin, secretin, enteropeptidase, trypsinogen, trypsin, chymotrypsinogen, chymotrypsin, endopeptidases, and exopeptidases.
• Amino acids are associated with specific carbon skeletons (alpha-ketoglutarate, pyruvate, oxaloacetate).
• Nitrogen transfer between carbon skeletons uses aminotransferases, glutamate dehydrogenase, glutamine synthetase, and glutaminase.
• The urea cycle purpose, regulation, and physiological alterations during defects are essential to understand.
• Liver and kidney roles in urea and ammonia production and elimination are vital.

Nitrogen Metabolism

• Nitrogen metabolism includes amino acid, protein, heme, and nucleotide metabolisms.
• Humans lack nitrogen storage forms, unlike glucose (glycogen) and lipids (TAGs, cholesterol).

Nitrogen Turnover

• Most nitrogen enters the body as amino acids.
• Contributions to the amino acid pool include dietary protein, protein turnover in the body, and synthesis of nonessential amino acids.
• Amino acids are removed from the pool for protein synthesis, synthesis of other compounds (nucleotides and heme), and use of amino acid carbon skeletons for other compounds (glucose, lipids, or energy).

Protein Digestion

• Protein must be broken down into amino acids or peptides for absorption.
• Stomach acid denatures proteins and kills microorganisms.
• Pepsin, an endopeptidase, is the main enzyme for protein digestion in the stomach.
• Pepsinogen, an inactive precursor, is converted to pepsin by the low pH in the stomach.
• Pepsin activates other pepsinogen molecules.
• Small intestine enzymes for protein digestion include pancreatic enzymes (trypsin, chymotrypsin, elastase, carboxypeptidase) and intestinal enzymes.
• Cholecystokinin and secretin stimulate pancreatic secretion.

Removal of Nitrogen and Transport

• Nitrogen transfer primarily involves the alpha-ketoglutarate skeleton.
• Aminotransferases catalyze transfer between amino acids and alpha-keto groups.
• Examples of aminotransferases like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are important in medicine as indicators of tissue damage.
• Glutamate dehydrogenase removes ammonia from glutamate, forming alpha-ketoglutarate.
• Glutamine synthetase adds ammonia to glutamate, forming glutamine.
• Glutaminase releases ammonia from glutamine.
• Removal of nitrogen from various tissues occurs through glutamine and alanine transport.

Urea Cycle

• Urea is the primary nitrogen excretion form.
• Urea cycle steps:
  • Carbamoyl phosphate synthetase I (CPS-I) is the rate-limiting step, using CO2 and ammonia to create the required component.
  • Ornithine transcarbamylase forms citrulline.
  • Citrulline is then transported to the cytoplasm where its reactions continue in the urea cycle
  • Enzymes involved in the urea cycle include aspartate transcarbamoylase, argininosuccinate synthetase, argininosuccinase, arginase.
• Regulation (activation) of CPS-I occurs via N-acetylglutamate for increased urea cycle function, usually with high levels of protein.
• Urea synthesized is released into the bloodstream and filtered by kidneys, excreted in urine.
• Defects in enzymes of the urea cycle (such as Orinithine transcarbamylase deficiency) lead to hyperammonemia.

Hyperammonemia

• Defects in urea cycle enzymes lead to hyperammonemia.
• Hyperammonemia is a severe condition related to inborn errors of metabolism.
• Understanding the impact of these genetic defects on metabolic pathways is vital for treatment approaches.

This quiz focuses on the urea cycle and the biochemical processes involved in protein digestion. It covers the roles of various enzymes and amino acids in the context of nitrogen balance and metabolic pathways. Test your understanding of these crucial biochemical concepts and their implications in physiology.