Untitled Quiz

Biochemistry II: Protein Digestion

• Dietary proteins are the primary source of nitrogen metabolized by the body. All nitrogen-containing compounds are synthesized from amino acids.
• Proteins are continuously synthesized and degraded, influencing cellular amino acid pools.
• Compounds derived from amino acids include cellular proteins, non-steroidal hormones, purines/pyrimidines, neurotransmitters, heme of hemoglobin and cytochromes, creatine phosphate, and melanin.

Nitrogen Metabolism: Protein Digestion and Amino Acid Absorption

• Enzymes that digest proteins are produced as inactive precursors (zymogens) by the stomach and pancreas.
• These zymogens are secreted into the digestive tract lumen and cleaved to smaller, active forms with proteolytic activity.
• Proteases break down dietary proteins into amino acids in the stomach and intestine.
• Endopeptidases break down proteins within the chain, while exopeptidases remove amino acids from the terminal ends of the chain.

Protein Digestion

• Pepsin, produced in the stomach, is an enzyme that begins protein digestion by hydrolyzing proteins into smaller polypeptides.
• Pancreatic proteases (trypsin, chymotrypsin, elastase, and carboxypeptidases) cleave polypeptides into oligopeptides and amino acids in the small intestine.
• Aminopeptidases on the intestinal brush border further cleave oligopeptides into individual amino acids.

Digestion in Stomach

• Chief cells secrete pepsinogen (a zymogen).
• Parietal cells secrete hydrochloric acid (HCl).
• HCl activates pepsinogen into pepsin through an autocatalytic conversion.
• Dietary proteins are denatured at the low pH of the stomach.

Digestion in Small Intestine

• Pancreatic juice (containing proteases) enters the duodenum.
• Enteropeptidase, secreted by the brush border, activates trypsinogen into trypsin.
• Trypsin activates other pancreatic enzymes (chymotrypsin, elastase, and carboxypeptidases).
• Endopeptidases (trypsin, chymotrypsin, elastase) break down peptides into smaller peptides, which are then cleaved by exopeptidases (carboxypeptidases and aminopeptidases).

Amino Acid Absorption by Intestinal Epithelial Cells

• Amino acids are absorbed from the intestinal lumen through secondary active transport aided by sodium (Na+) and facilitated diffusion.

Amino Acid Pool Replenishment

• Proteins are recycled within cells, and examples of high-turnover proteins include hemoglobin, muscle proteins, and digestive enzymes.
• Excess dietary protein is converted to glycogen and triglycerides for storage.

Protein Turnover

• Lysosomal proteases (cathepsins) degrade proteins that enter lysosomes.
• Cytoplasmic proteins targeted for breakdown are tagged with ubiquitin, which targets them to the proteasome for degradation.

Proteases Involved in Protein Turnover/Degradation

• Different protease classes and mechanisms are responsible for breaking down different proteins.
• Cathepsins are lysosomal enzymes; and Caspases are a class of enzymes involved in apoptosis, while Proteasomes degrade ubiquinitated proteins.

Mechanisms of Protein Degradation

• Autophagy: Cytoplasm is sequestered into vesicles and degraded in lysosomes by lysosomal enzymes.
• Ubiquitin−proteasome pathway: Ubiquitin-tagged proteins are degraded by proteasomes in an ATP-dependent manner.

Nitrogen Metabolism

• Nitrogen removal precedes the oxidation of amino acid carbon skeletons.
• Branched-chain amino acids can be oxidized in many tissues but must travel to the liver for nitrogen disposal.
• Ammonia, a product of amino acid nitrogen removal, is toxic and converted to urea in the liver.

Urea Cycle

• The urea cycle converts toxic ammonia to non-toxic, water-soluble urea for excretion in urine.

Dietary Protein Metabolism

• Dietary proteins are digested in the stomach and intestine into amino acids.
• These are then absorbed into the blood, to be used by cells for protein synthesis or catabolized.

Transamination

• Transamination is the primary process for removing nitrogen from amino acids.
• An amino group is transferred from one amino acid to a keto acid.
• Pyridoxal phosphate (PLP) derived from vitamin B6 is needed as a coenzyme.
• Transamination reactions are readily reversible, used in both amino acid breakdown and synthesis.

Additional notes

• Hartnup disease: An inherited disorder impacting the transport of neutral amino acids.
• Cystinuria: A genetic disorder characterized by impaired transport of cysteine, lysine, arginine, and ornithine, leading to potential kidney stones.
• Cystinosis: A rare disorder marked by cystine accumulation within lysosomes and leading to renal failure.
• Maple syrup urine disease: A genetic condition causing the accumulation of branched-chain amino acids, leading to neurologic issues.
• Clinical conditions (e.g., Kwashiorkor, Marasmus) affecting protein intake

Sources of Urea

• Urea is generated from amino acid breakdown.
• Amino acids are partially oxidized to produce energy in the body.

Degradation Pathways

• Gluconeogenesis produces glucose from amino acids.
• Ketogenesis produces ketone bodies from amino acids.
• Various pathways exist for different amino acid degradation processes.

Clinical Notes and Considerations

• Several genetic disorders affect amino acid metabolism, leading to specific health consequences.
• Clinical features of specific metabolic disorders vary with respect to the affected enzyme, resulting in different symptoms.

Additional considerations for protein turnover and degradation

• The various enzymes involved in these processes have specific roles within metabolic pathways.
• Some clinical implications of issues with these particular processes, or the resultant symptoms.