Individuals with a deficiency in pancreatic secretion, due to conditions like chronic pancreatitis, cystic fibrosis, or surgical removal of the pancreas, experience incomplete digestion and absorption of fat and protein. This leads to the abnormal presence of lipids in the feces, known as steatorrhea, and undigested protein.
Celiac disease, also known as celiac sprue, is a malabsorption disorder caused by immune-mediated damage to the small intestine triggered by the consumption of gluten, a protein found in wheat, barley, and rye.
Digestion of oligopeptides in the small intestine occurs through the action of aminopeptidase, an exopeptidase found on the luminal surface of the enterocytes. It repeatedly cleaves the N-terminal residue from oligopeptides, resulting in smaller peptides and free amino acids.
The majority of free amino acids are transported into enterocytes through sodium-dependent secondary active transport via solute carrier (SLC) proteins on the apical membrane. Several transport systems with overlapping amino acid specificities exist. Di- and tripeptides, however, are taken up through a proton-linked peptide transporter (PepT1). Subsequently, the peptides are hydrolyzed into free amino acids. Free amino acids, regardless of their source, are released from enterocytes into the portal system through sodium-independent transporters on the basolateral membrane. Thus, only free amino acids are present in the portal vein after consuming a protein-rich meal. These amino acids are either metabolized by the liver or released into the general circulation. (Note: Branched-chain amino acids, or BCAA, are not metabolized by the liver but are transported from the liver to muscle via the bloodstream.)
The small intestine and proximal tubules of the kidneys share common transport systems for amino acid uptake. Consequently, a defect in any of these systems results in an inability to absorb specific amino acids in the intestine and kidney tubules. For instance, a carrier system responsible for the uptake of cystine and the dibasic amino acids ornithine, arginine, and lysine (referred to as COAL) may be defective in the inherited disorder cystinuria. As a result, all four amino acids are excreted in the urine. Cystinuria occurs in approximately 1 in 7,000 individuals, making it one of the most common inherited diseases and the most prevalent genetic error of amino acid transport. Clinically, this condition leads to the formation of kidney stones (calculi) due to the precipitation of cystine, which can obstruct the urinary tract. Adequate oral hydration is a crucial aspect of cystinuria treatment. (Note: Defects in the uptake of tryptophan through a neutral amino acid transporter can cause Hartnup disorder, resulting in dermatologic and neurologic symptoms similar to pellagra.)
Nitrogen removal from amino acids is essential for their energy production and is a mandatory step in the catabolism of all amino acids. The α-amino group present in amino acids protects them from oxidative breakdown. Through transamination and oxidative deamination, reactions described in this section, the α-amino group is removed, ultimately providing ammonia and aspartate, which serve as sources of urea nitrogen.
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