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portal vein and leaves by way of the central vein. Glutaminase and urea cycle enzymes are concentrated in the periportal hepatocytes, while glutamine synthetase is found exclusively in perivenous hepatocytes (see p. 450). During alkalosis, glutamine enters the periportal cells and is hydrolyzed to contribute ammonium ion for urea synthesis. The bulk of glutamine and ammonium nitrogen entering the liver leaves the liver as urea. The perivenous cellular location of glutamine synthetase is important because some ammonium ions escape conversion to urea. This enzyme traps much of this toxic compound in the form of glutamine. Thus glutamine is released from the liver and circulates back to the liver where it reenters the glutamine cycle in the periportal hepatocytes. Thus, in liver, both donation of ammonium ion by glutamine for urea synthesis and the synthesis of glutamine are important in maintaining low blood ammonium levels. In acidosis, glutaminase of the periportal hepatocytes (unlike the renal glutaminase isozyme) is less active and much of the blood glutamine escapes hydrolysis in the liver. Likewise, carbamoyl phosphate synthetase of periportal hepatocytes is less active in acidosis, permitting perivenous cells to convert more ammonium ion to glutamine, which is then available for metabolism by the kidney to yield hydrogen ions that need to be eliminated in the urine.
The Colon Salvages Energy from the Diet
Unlike the small intestine, which uses glutamine for its major energy source, the colon utilizes short­chain fatty acids: butyrate, propionate, isobutyrate, and acetate (Figure 13.19). It obtains most of these fatty acids from the lumen of the colon, where bacteria produce them by fermentation of unabsorbed dietary components. These short­chain fatty acids would otherwise be lost in stool, so their use by cells of the colon (colonocytes) represents a way of gaining as much energy from dietary sources as possible. If produced in excess of the needs of the colon, short­chain fatty acids pass into the portal blood for use by the liver. Interestingly, colonocytes can produce ketone bodies from butyrate, presumably releasing them into the portal blood for use as fuel by extrahepatic tissues. When surgery is performed that bypasses the colon (e.g., an ileostomy), some patients develop a form of colitis called diversion colitis. In some cases, providing enemas containing the short­chain fatty acids has healed the colitis.
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