Protein Digestion, Absorption, and Ammonia Disposal

Important Topics Covered:
- Protein digestion and absorption
- Protein quality
- Turnover
- Recommended intake
- Deficiency objectives

Protein Digestion:
- Begins in the stomach with the secretion of a proenzyme called pepsinogen.
- Pepsinogen is autocatalytically converted to Pepsin, initiating proteolysis.
- Most proteolysis occurs in the duodenum due to pancreatic enzyme activities.
Enzymes:
- Pancreatic secretions contain serine proteases and zinc peptidases, produced in proenzyme forms.
- These proteases act as both endopeptidases and exopeptidases.
- Resulting products: amino acids, dipeptides, and tripeptides are absorbed by enterocytes of the mucosal wall.

Secretion Triggers:
- Presence of food in the intestinal lumen triggers proenzyme secretion.
Hormones Released:
- Cholecystokinin (CCK) and secretin secreted by mucosal endocrine cells into circulation.
- CCK and secretin:
- Cause contraction of gallbladder.
- Stimulate exocrine pancreatic secretion of bicarbonate-rich alkaline fluid containing protease proenzymes.
Activation by CCK:
- CCK stimulates secretion of enteropeptidase, which activates trypsinogen to trypsin.
- Trypsin activates all other proenzymes, generating active proteases and peptidases for dietary polypeptide hydrolysis.

Gastric cells release gastrin, leading to gastric juice release.
Partially digested proteins enter the small intestine, causing releases of secretin and CCK.
Pancreatic proenzymes transform to active enzymes in the small intestine to digest polypeptides into smaller units.
Hydrochloric acid in gastric juice denatures proteins, activating pepsin.
Intestinal lumen enzymes complete protein digestion.

Zymogen Enzyme Activity:
- Pepsinogen → Pepsin: Active in stomach, cleaves peptide bonds, yielding peptides.
- Trypsinogen → Trypsin
- Cleaves basic amino acids to yield smaller peptides and free amino acids.
- Chymotrypsinogen → Chymotrypsin: cleaves aromatic amino acids.
- Procarboxypeptidases: Produce free amino acids from C-terminal residues.
- Aminopeptidases: Produce free amino acids from N-terminal residues.

Transport Mechanism:
- End products of digestion enter the body from the lumen of the GI tract through:
- Brush border membrane
- Basolateral membrane
Amino Acid Transport:
- Small peptides and amino acids move via diffusion, facilitated diffusion, or active transport through enterocytes to the portal circulation.

Post absorption:
- Amino acids enter portal blood and travel to various tissues.
- Uptake occurs via carrier systems similar to those in intestinal membranes.

Sodium binds to the amino acid transporter, which increases the carrier's affinity for the amino acid.
Transport Process:
- Sodium is pumped out by Na⁺, K⁺-ATPase, forming a sodium-amino acid-cotransporter that delivers both into the cytosol.

Hartnup Disorder:
- Autosomal recessive impairment of neutral amino acid transport, particularly for tryptophan.
- Characterized by hyperaminoaciduria, and reduced tryptophan affects niacin synthesis; leads to pellagra-like symptoms.

Protein Types:
- Complete Protein: Contains all essential amino acids.
- Incomplete Protein: Lacks one or more essential amino acids.
- Mutual Supplementation: Combining different protein sources to achieve complete amino acid profiles.
Protein Synthesis and Degradation:
- Controlled independently; rates vary during growth or illness/injury.
- Body protein turnover is about 1–2% per day, totaling over 300 g.
- Proteins are primarily degraded by proteases in lysosomes and proteasomes.

Function:
- Lysosomes degrade proteins, nucleic acids, lipids, carbohydrates, etc.
- No energy required; amino acids released can be reused for protein synthesis or degraded.
Autophagy:
- Involves degradation of cytosolic constituents through lysosomal mechanisms.

Proteasomes Structure:
- Oligomeric structures with central cavities for degradation.
- Ubiquitination is an ATP-dependent process marking proteins for degradation.
- Proteins typically degraded include damaged, mis-located, or regulatory proteins.
- Increased action during starvation and in conditions such as sepsis and cancer.

Kwashiorkor:
- Insufficient protein with adequate energy; leads to edema due to loss of blood proteins.
Marasmus:
- Resulting from chronic energy and protein insufficiency, causing emaciation.

Transamination: Transfer of amino group from one amino acid to an α-keto acid.
Deamination: Removal of amino group resulting in free ammonia.

Free ammonia, due to its toxicity, is transported to the liver mostly in the form of alanine and glutamine through transamination.

Neurotoxicity: Elevated blood ammonia leads to severe brain damage; affects neurotransmitter balance and may cause cerebral edema.
Ureotelic Organisms: Convert excess NH₄⁺ to urea for excretion via the urea cycle.

First cyclic metabolic pathway discovered, proposed by Hans Krebs and Kurt Henseleit in 1932.
Reactions: Involves multiple steps in mitochondrial and cytosolic environments, starting with ammonia and CO₂.
Enzymes involved include carbamoyl phosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, and arginase.

Hyperammonemia Type I: Due to carbamoyl phosphate synthetase deficiency, leading to ammonia accumulation.
Hyperammonemia Type II: Results from ornithine transcarbamoylase deficiency, characterized by elevated glutamine levels.
Citrullinemia: Deficiency in argininosuccinate synthetase; high citrulline excretion.
Argininosuccinic Aciduria: Elevated argininosuccinate due to argininosuccinase deficiency.
Hyperargininemia: Arginase deficiency leading to elevated arginine levels in blood and cerebrospinal fluid. Key treatment involves dietary protein restriction.