Chapter 18 Amino Acid Oxidation and the Production of Urea Carnivores can obtain up to 90 of their energy requirements from amino acid oxidation whereas herbivores may fill only a small fraction of their energy needs by this route In animals amino acids undergo degradation in three different metabolic circumstances o During the normal synthesis and degradation of cellular proteins some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation o When a diet is rich in protein and the ingested amino acids exceed the body s needs for protein synthesis the surplus is catabolized amino acids cannot be stored o During starvation or in uncontrolled diabetes mellitus when carbohydrates are either unavailable or not properly utilized cellular proteins are used as fuel Amino acids lose their amino groups to form keto acids which undergo oxidation to CO2 and H2O or provide three and four carbon units that can be converted by gluconeogenesis into glucose 18 1 Metabolic Fates of Amino Groups Amino acids derived from dietary protein are the source of most amino groups Most amino acids are metabolized in the liver Dietary Protein Is Enzymatically Degraded to Amino Acids In humans the degradation of ingested proteins to their constituent amino acids occurs in the gastrointestinal tract o Entry of dietary protein into the stomach stimulates the secretion of gastrin a hormone that stimulates the secretion of hydrochloric acid by parietal cells and pepsinogen by the gastric glands Acidic gastric juice is an antiseptic and a denaturing agent o Pepsinogen by an autocatalytic cleavage that occurs at low pH an inactive precursor that is converted to active pepsin Pepsin hydrolyzes ingested proteins at peptide bonds on the amino terminal side of the aromatic amino acids o As the acidic stomach contents pass into the small intestine the low pH triggers secretion of secretin into the blood Stimulates the pancreas to secrete bicarbonate into the small intestine to neutralize the gastric HCl increasing the pH o Arrival of amino acids in the upper part of the intestine causes release o Trypsinogen of cholecystokinin into the blood chemotrypsinogen and procarboxypeptidases A and B are the zymogens of trypsin chymotrypsin and carboxypeptidases A and B Synthesized and secreted by the exocrine cells of the pancreas Trypsinogen is converted to trypsin the active form by enteropeptidase a proteolytic enzyme secreted by intestinal cells Free trypsin catalyzes the conversion of additional trypsinogen to trypsin Trypsin also activates chymotrypsinogen the procarboxypeptidases and proelastase Synthesis of the enzymes as inactive precursors protects the exocrine cells from destructive proteolytic attack Pancreatic trypsin inhibitor a specific inhibitor that effectively prevents premature production of active proteolytic enzymes within the pancreatic cells Trypsin and chymotrypsin hydrolyze the peptides that were produced by pepsin in the stomach o Very efficient because of specificity o Degradation of the short peptides in the small intestine is then completed by other intestinal peptidases Carboxypeptidases A and B remove successive carboxyl Aminopeptidase terminal residues from peptides residues from short peptides hydrolyzes successive amino terminal o The resulting mixture of free amino acids is transported to the epithelial cells lining the small intestine through which they enter the blood capillaries in the villi and travel to the liver Acute pancreatitis by which pancreatic secretions enter the intestine a disease caused by obstruction of the normal pathway o The zymogens of the proteolytic enzymes are converted to their catalytically active forms prematurely and attack the pancreatic tissue itself Pyridoxal Phosphate Participates in the Transfer of Amino Groups to Ketoglutarate The first step in the catabolism of most L amino acids once they have reached the liver is the removal of the amino groups o Promoted by aminotransferases or transaminases o Transamination atom of ketoglutarate leaving an keto acid analog the amino group is transferred to the carbon o The effect is to collect the amino groups in the form of L glutamate which then functions as an amino group donor Pyridoxal phosphate PLP the prosthetic group of aminotransferases o The coenzyme form of pyridoxine or vitamin B6 o Functions as an intermediate carrier of amino groups at the active site of aminotransferases o Reacts at the carbon of amino acids through racemization decarboxylations and transaminations Glutamate Releases Its Amino Group As Ammonia in the Liver In hepatocytes glutamate is transported from the cytosol to the mitochondria where it undergoes oxidative deamination o Catalyzed by L glutamate dehydrogenase The only enzyme that can use NAD OR NADP Transdeamination glutamate dehydrogenase the combined action of an aminotransferase and Glutamate dehydrogenase is an allosteric enzyme with six identical subunits o Positively regulated by ADP o Negatively regulated by GTP Hyperinsulinism hyperammonemia syndrome when there are elevated levels of ammonia in the blood and hypoglycemia caused by permanent activation of glutamate dehydrogenase Glutamine Transports Ammonia in the Bloodstream Nucleotide degradation generates free ammonia o In most animals this free ammonia is converted to a nontoxic compound before being transported to the liver or kidney The free ammonia is combined with glutamate by glutamine synthetase Requires ATP Two steps o Glutamate and ATP react to form ADP and a glutamylphosphate intermediate o Glutamylphosphate reacts with ammonia to produce glutamine and inorganic phosphate In most terrestrial animals glutamine in excess is transported to the intestine liver and kidneys for processing o The amide nitrogen is released as ammonium ion in the mitochondria where glutaminase converts glutamine to glutamate and NH4 Most glutamate enters the transamination reactions Alanine Transports Ammonia from Skeletal Muscles to the Liver Glucose alanine cycle in a nontoxic form using alanine pyruvate forming alanine which travels to the liver Alanine aminotransferase transfers the amino group on glutamine to a pathway that transports amino groups to the liver o Alanine aminotransferase then transfers the amino group from alanine to ketoglutarate forming pyruvate and glutamate o Glutamate can then enter the mitochondria where the glutamate dehydrogenase reaction
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