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 degradationo 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 glucose18.1 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 liverDietary Protein Is Enzymatically Degraded to Amino Acids- In humans, the degradation of ingested proteins to their constituent amino acids occurs in the gastrointestinal tracto 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 agento Pepsinogen – an inactive precursor that is converted to active pepsin by an autocatalytic cleavage that occurs at low pH Pepsin hydrolyzes ingested proteins at peptide bonds on the amino-terminal side of the aromatic amino acidso 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 pHo Arrival of amino acids in the upper part of the intestine causes releaseof cholecystokinin into the bloodo Trypsinogen , 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 stomacho Very efficient because of specificityo Degradation of the short peptides in the small intestine is then completed by other intestinal peptidases Carboxypeptidases A and B – remove successive carboxyl-terminal residues from peptides Aminopeptidase – hydrolyzes successive amino-terminal residues from short peptideso 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 – a disease caused by obstruction of the normal pathway by which pancreatic secretions enter the intestineo The zymogens of the proteolytic enzymes are converted to their catalytically active forms prematurely and attack the pancreatic tissueitselfPyridoxal 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 groupso Promoted by aminotransferases or transaminaseso Transamination – the -amino group is transferred to the -carbon atom of -ketoglutarate, leaving an -keto acid analogo 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 aminotransferaseso The coenzyme form of pyridoxine, or vitamin B6o Functions as an intermediate carrier of amino groups at the active siteof aminotransferaseso Reacts at the carbon of amino acids through racemization, decarboxylations, and transaminationsGlutamate 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 – the combined action of an aminotransferase and glutamate dehydrogenase- Glutamate dehydrogenase is an allosteric enzyme with six identical subunitso Positively regulated by ADPo 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 dehydrogenaseGlutamine Transports Ammonia in the Bloodstream- Nucleotide degradation generates free ammoniao 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 intermediateo -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 processingo The amide nitrogen is released as ammonium ion in the mitochondria,where glutaminase converts glutamine to glutamate and NH4+- Most glutamate enters the transamination reactionsAlanine Transports Ammonia from Skeletal Muscles to the Liver- Glucose-alanine cycle – a pathway that transports amino groups to the liver in a nontoxic form using alanine- Alanine aminotransferase – transfers the -amino group on glutamine to pyruvate, forming alanine, which travels to the livero Alanine
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