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Protein catabolism is the breakdown of proteins into absorbable monomers for further degradation or reassembly. Protein catabolism in the intestinal lumen is important for several reasons, 1 of which is mobilizing essential amino acids for absorption. Essential amino acids can’t be synthesized in the human body but are needed for the biosynthesis of vital proteins, so their only source is polypeptide breakdown through digestive enzymes. This process begins in the stomach and continues in the small intestine. Large protein chains are disassembled to eventually leave free amino acids that can be taken into the blood and transported to various cells around the body for further breakdown. The stomach mucosa and the exocrine pancreas release endopeptidases in zymogen form to cleave the polypeptide chain between particular amino acid residues. Once in a smaller form, exopeptidases remove the last amino acids from the C or N terminus of a di-peptide or tri-peptide 1 by 1, aiding absorption at the microvilli. Cells can use those amino acids to construct vital proteins or as substrates for energy creation. Proteins created intracellularly can also be catabolized for the same reasons. Intracellular proteins that were either misfolded or are no longer functioning in the cell also undergo intracellular protein catabolism in the lysosome, with the help of ubiquitin and proteasome formation. Suppose a cell is in a low-energy state. In that case, the free amino acids in the cytosol are further degraded to produce citric acid cycle intermediates and are funneled there to produce ATP. While the carbon backbone enters energy-generating pathways, the nitrogen backbone is modified and excreted mainly through the kidneys.

Cystic Fibrosis is an autosomal recessive mutation in the CFTR gene, which codes the proteins that compose the chloride channel pore.[23] The severity of the disease varies, but some features are common to all forms, for example, the formation of thick mucus plugs in the pancreatic duct, the lungs, and the male genitourinary system. Because proteins must break down to be absorbed, a mucus plug blocking the zymogen release from the exocrine pancreas would lead to the absence of vital protein catabolism in the intestinal lumen.[23] Patients with cystic fibrosis have severe protein deficiency. They must receive exogenous pancreatic enzyme supplementation, though it bears mention that the side effects of long-term pancreatic enzyme supplementation are unknown at this time.[24] Kwashiorkor is another severe protein deficiency; however, it is due to a lack of protein intake rather than a genetic disorder. The digestive enzymes are present in kwashiorkor; however, because there is little protein ingested, symptoms of protein deficiency are present. In malnourished individuals with kwashiorkor, the vital reactions in the body are sustained through intracellular protein catabolism. The need for essential amino acids leads to an extensive reduction in peripheral muscle mass from muscle breakdown.[10] Protein deficiency also leads to decreased serum levels of albumin, thus decreasing intravascular colloid pressure, which leads to edema and abdominal distention. Severe kwashiorkor quickly deteriorates because digestive enzymes are no longer produced, and the small intestinal epithelium is not regenerated.

Kwashiorkor is another severe protein deficiency; however, it is due to a lack of protein intake rather than a genetic disorder. The digestive enzymes are present in kwashiorkor; however, because there is little protein ingested, symptoms of protein deficiency are present. In malnourished individuals with kwashiorkor, the vital reactions in the body are sustained through intracellular protein catabolism. The need for essential amino acids leads to an extensive reduction in peripheral muscle mass from muscle breakdown.[10] Protein deficiency also leads to decreased serum levels of albumin, thus decreasing intravascular colloid pressure, which leads to edema and abdominal distention. Severe kwashiorkor quickly deteriorates because digestive enzymes are no longer produced, and the small intestinal epithelium is not regenerated. A defect in facilitated and active transport mechanisms can lead to pathological malabsorptive states. Cystinuria and Hartnup disease are genetic disorders involving the membrane amino acid transporters but differ in the groups of amino acids transported and present differently clinically.[9] Cystinuria is a defect in transporting basic amino acids through the membranes of the renal and gastrointestinal systems. The hallmark presentation of this disorder is the formation of renal calculi due to the inability to resorb the basic amino acid cystine from the glomerular filtrate. Because the transporter also exists in the small intestine epithelium, cystine and other basic amino acids are not well absorbed from the intestinal lumen. A mechanistically similar disorder, Hartnup disease is a defect in transporting neutral amino acids across the renal and intestinal systems. Because tryptophan is 1 of the neutral amino acids poorly absorbed, a pellagra-like presentation of rash, diarrhea, and psychiatric disturbances is present on physical exam. Unlike pellagra, supplementation with niacin has little resolution of symptoms and should reveal the need for genetic testing.