Molecular Biology

Terms	Definitions
AA Cat Plants	...
AA Concen Plant Tissue	...
Amino Acids Undergo Degradation in three different metabolic circumstances	1. During normal synthesis and degradion of cellular proteins, some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation. 2. When a diet is rich in protein and the ingested amino acid exceeds the body's needs for protein synthesis, the surplus is catabolized; amino acids cannot be stored. 3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, cellular proteins are used.
Amino Acids Undergo Degradation in three different metabolic circumstances (Loss of NH2)	1. Loose of Amino Group 2. Become Alpha Keto-Acid (Carbon Skeleton of AA) 3. The Alpha Keto-Acid undergo oxidation to CO2 and H2O, or more importantly provide 3 or 4 carbon units that can be converted by gluconeogensis > glucose. The fuel for brain, skeletal muscle, and other tissues.
Figure 18-1 Overview of AA Catabolism in mammals
Metabolic Fates of Amino Groups	1. N2 is abundant in the atmosphere, but is too inert for most biochemical processes. 2. Only a few microorganisms have the ability to convert N2 to biologically useful form such as NH3, Amino groups are carefully integrated into biological systems. 3. Dietary Protein is the main source of Amino Groups. 4. Metabolized in the Liver 5. Some of the ammonia generated created is recycled and used in several pathways (Excreted or Converted to Urea or Uric Acid for Excretion) 6. Excess ammonia created in other tissue travels to the liver as amino groups for conversion to excretory forms. ---------- 1. Glutamate and Glutamine are important in nitrogen metabolism (Collection Point for Amino Groups) 2. In Cytoplasm of Hepatocytes: Amino Group of AA are transfered to Alpha-Ketoglutarate > Glutamate 3. Glutamate enters the mitochondria and gives up the NH4 4. Excess ammonia is converted amide nitrogen of glutamine --> Passes to the liver and then to mitochondria. 5. In skeletal muscle excess amino groups are transfered to pyruvate to form alanine, important in transport of Amino groups to the liver.
Figure 18-2 Amino Group Catabolism
Dietary Protein is Enzymatically Degraded to Amino Acids	Entry of dietary protein into the stomach stimulates the gastric mucosa to secrete the hormone gastrin.
Gastrin	1. Stimulates the secretion of hydrochloric acid by the parietal cells and pepsinogen by the chief cells of the gastric gland 2. The acidic gastric juice is both na antiseptic (kills most bacteria and other foreign cells), and denaturing agent (unfolding globular proteins and rendering the internal peptide bonds more accessible to enzymatic hydrolysis).
Pepsinogen	1. Pepsinogen - active precursor (zymogen) is converted to pepsin by autocatalytic cleavage (mediated by pepsinogen) - low pH. 2. In the Stomach, Pepsin hydrolyzes ingested proteins at the peptide bonds on the Amino-Terminal side of the aromatic AA residue Phe, Trp, Tyr, cleaving long polypeptide chains into a mixture of smaller peptides.
Zymogen	An inactive precursor of an enzyme, activated by various methods (acid hydrolysis, cleavage by another enzyme, etc.)
Secretin	1. As the acidic stomach content passess into the small intestine, the low pH triggers the secretion of hormone Secretin into blood. 2. Secretin stimulates the pancreas (by way of the pancreatic duct) to secrete bicarbonate into the small intestine, neutralizes the gastic HCl, abruptly increases the pH to about 7. 3. The digestion of proteins now continues in the Small intestine. 4. Arrival of the AA in the upper part of the intestine the (duodenum) > causes a release of hormone cholescystokinin into blood.
Cholecystokinin	1. Stimulates secretion of several pancreatic enzymes with activity at pH 7 to 8. 2. Enzymes - 1. Trypsinogen - 2. Chymotrypsinogen - 3. Procarboxypeptidase A - 4. Procarboxypeptidase B - 5. Trypsin - 6. Chymotrypsin - 7. Carboxypeptidase A - 8. Carboxypeptidase B 3. These enzymes are secreted by the exocrine cells of the pancreas.
Part of the Human digestive (gastrointestinal) tract
Enteropeptidase	1. Converts Trypsinogen to active form Trypsin. 2. Enteropeptidase is a proteolytic enzyme secreted by the intestinal cells. 3. Free trypsin catalyzes the conversion of additional trypsinogen to trypsin. 4. Also activated chymotrypsinogen, procarboxypeptidases, proelastase.
Why this elaborate mechanism for getting active digestive enzymes into the gastrointestinal tract?	1. Synthesis of enzymes in their inactive precursors protects the exocrine cells from destructive proteolytic attack. 2. The pancreas further protects itself against self-digestion by making a specific inhibitor > Pancreatic Trypsin Inhibitor
Pancreatic Trypsin Inhibitor	1. Pancreas further protects itself against self-digestion. 2. Prevents immature production of active proteolytic enzymes within the pancreatic cells.
Further Hydrolysis & Digestion	1. Trypsin and Chymotrypsin further hydrolyze the peptides that where produced by pepsin in the stomach. 2. This stage is very efficient because Pepsin, Trypsin, Chymotrypsin have AA specificity. 3. The degradtion of the short pepetides in the small intestine is completed by other intestinal peptidases - Carboxypeptidases A B (Zinc-Containing) * Remove successive carboxyl-terminal residues from peptides. - Aminopeptidase
Aminopeptidase	1. Hydrolyzes successive amino-terminal residues from short peptides. 2. The resulting mixture of free AA are transported into the epithelial cells lining the small intestine. 3. AA enter the blood capillaries in the villi and travel to the liver. 4. Most globular proteins from animal sources are almost completely hydrolyzed to AA in the GIT, but some fibrous proteins, such as keratin, are only partly digested. 5. Some plant AA are protected against breakdown by cellulose (indigestible)
Acute Pancreatitis	1. Disease caused by the obstruction of the normal pathway by which pancreatic secretions enter the intestine. 2. The zymogens of proteolytic enzymes are converted to their active forms prematurely inside the pancreas cells and attack the pancreatic tissue. 3. Causes excruciating pain and damage to organ that can be fatal.
Pyridoxal Phosphate Participates in the Transfer of Alpha-Amino Groups to Alpha-Ketoglutarate	...
Aminotransferases and Transaminases	1. After AA have reached the liver. 2. The Amino group is removed by this enzyme.
Transamination	1. The alpha-amino group is transfered to the alpha-carbon of alpha-ketoglutarate. 2. Leaves behind the alpha-keto acid. 3. There is no net deamination in this reaction. BC alpha-ketoglutarate becomes aminated as the AA is deaminated. 4. Forms Glutamate.
Enzyme-Catalyzed Transaminations
Glutamate	1. Acts as amino group donor for biosynthetic pathways or for excretion pathways that lead to the elimination of nitrogenous waste products. 2. Cells contain different types of aminotransferases. Many are specific for Alpha-Ketoglutarate as the Amino Group acceptor but differ in their specificity for the AA. The enzymes are named for the Amino group donor. (Alanine Transferase) (Reversible, Equilibrium Constant 1.0, dG 0 kj/mol)
Pyridoxal Phosphate (PLP)	1. Prosthetic Group 2. The coenzyme form of pyridoxine, or Vit B6. 3. The Primary Role in cells is in metabolism of molecules with amino groups. ----------- 4. Functions as an intermediate carrier of Amino groups at their active site of aminotransferases. 5. Undergoes reversible transformations between its aldehyde form, (Pyridoxal Phosphate) > Accepts Amino Group, and its aminated form (Pyridoxamine Phosphate) 6. Pyridoxal Phosphate is covalently bound to enzymes active site through an aldimine (Schiff base) linkage to the amino group of Lys residue.
Pyridoxal Phosphate, the prosthetic group of aminotransferases
Box 18-1 (Assays of Tissue Damage)	...
Glutamate Releases Its Amino Group as Ammonia in the Liver	1. The amino group of the glutamate molecules must be removed to prepare them for excretion. 2. In the hepatocytes, glutamate is transported into the mitochondria where it undergoes oxidative deamination (catalyzed by glutamate dehydrogenase). 3. This enzyme is found in the mitochondrial matrix & can use either NAD or NADP+ as the acceptor of reducing equivalents.
Transdeamination	1. The combined actions of the aminotransferase and the glutamate dehydrogenase. 2. A few AA bypass the transdeamination pathway and undergo direct oxidation deamination (Section 18.2) . 3. Glutamate dehydrogenase operates at an important intersection of carbon and nitrogen metabolism. (Allosteric Enzyme)
Allosteric Enzyme	1. Contains 6 identical subunits. 2. Influenced by a complex array of allosteric modulators. 3. Positive Modulator ADP and the Negative Modulator GTP. 4. Mutations that alter either the allosteric binding site for GTP or other wise cause permanent activation of glutamate dehydrogenase lead to hyperinsulinism-hyperammoneia syndrome - Elevated levels of ammonia in the blood and hypoglycemia
Some amino acid transformations at the alpha carbon that are facilitated by pyridoxal phosphate
Reactions Catalyzed by Glutamate Dehydrogenase
Glutamine Transports Ammonia in the Bloodstream	...
Glutamine Synthetase	...
Glutaminase	...
Acidosis	...
Ammonia transport in the form of glutamine