Digestion abnormalities: In individuals with a deficiency in pancreatic secretion (for example, because of chronic pancreatitis, cystic fibrosis, or surgical removal of the pancreas), the digestion and absorption of fat and protein are incomplete. This results in the abnormal appearance of lipids in the feces (a condition called steatorrhea; see p. 177) as well as undigested protein.
Celiac disease (celiac sprue) is a disease of malabsorption resulting from immune-mediated damage to the small intestine in response to ingestion of gluten (or gliadin produced from gluten), a protein found in wheat, barley, and rye.
C. Digestion of oligopeptides by small intestine enzymes
The luminal surface of the enterocytes contains aminopeptidase, an exopeptidase that repeatedly cleaves the N-terminal residue from oligopeptides to produce even smaller peptides and free amino acids.
D. Amino acid and small peptide intestinal absorption
Most free amino acids are taken into enterocytes via sodium-dependent secondary active transport by solute carrier (SLC) proteins of the apical membrane. At least seven different transport systems with overlapping amino acid specificities are known. Di-and tripeptides, however, are taken up by a proton-linked peptide transporter (PepT1). The peptides are then hydrolyzed to free amino acids. Regardless of their source, free amino acids are released from enterocytes into the portal system by sodium-independent transporters of the basolateral membrane. Therefore, only free amino acids are found in the portal vein after a meal containing protein. These amino acids are either metabolized by the liver or released into the general circulation. [Note: Branched-chain amino acids (BCAA) are not metabolized by the liver but, instead, are sent from the liver to muscle via the blood.]
E. Absorption abnormalities
The small intestine and the proximal tubules of the kidneys have common transport systems for amino acid uptake. Consequently, a defect in any one of these systems results in an inability to absorb particular amino acids into the intestine and into the kidney tubules. For example, one system is responsible for the uptake of cystine and the dibasic amino acids ornithine, arginine, and lysine (represented as COAL). In the inherited disorder cystinuria, this carrier system is defective, and all four amino acids appear in the urine (Fig. 19.6). Cystinuria occurs at a frequency of 1 in 7,000 individuals, making it one of the most common inherited diseases and the most common genetic error of amino acid transport. The disease expresses itself clinically by the precipitation of cystine to form kidney stones (calculi), which can block the urinary tract. Oral hydration is an important part of treatment for this disorder. [Note: Defects in the uptake of tryptophan by a neutral amino acid transporter can result in Hartnup disorder and pellagra-like (see p. 384) dermatologic and neurologic symptoms.]
IV. NITROGEN REMOVAL FROM AMINO ACIDS
The presence of the α-amino group keeps amino acids safely locked away from oxidative breakdown. Removing the α-amino group is essential for producing energy from any amino acid and is an obligatory step in the catabolism of all amino acids. Once removed, this nitrogen can be incorporated into other compounds or excreted as urea, with the carbon skeletons being metabolized. This section describes transamination and oxidative deamination, reactions that ultimately provide ammonia and aspartate, the two sources of urea nitrogen (see p. 253).
A. Transamination: Funneling amino groups to glutamate