mod 11 Flashcards
dietary protein per day needed to maintain amino acid pool
70-100g dietary protein
proteolysis
process whereby peptide bonds within proteins are cleaved - hydrolytic rxn - proteolysis begins in the stomach and continues on in the small intestine
stomach secretes ____
gastric juice: pH of 2 (equivalent to 100mM HCl) - includes gastrin and pepsin
2 purposes of low pH of gastric juice
- denaturation/unfolding of proteins - makes the peptide bonds accessible to proteases
- serves as an antiseptic - destroys bacteria and viruses
gastrin
peptide hormone - primary role is to stimulate acid secretion into stomach
pepsin
protease - cleaves peptide bonds following a hydrophobic amino acids
pancreatic juice
secreted by pancreas into small intestine - neutralizes digestive slurry coming in from stomach to pH 7 with HCO3-
Also contains proteases that degrade proteins into free amino acids that are then absorbed by endothelial cells and then into the portal vein where they are transported throughout the body for utilization.:
- trypsin
- chymotrypsin
- elastase
- carboxypeptidases and aminopeptidases
trypsin cleaves ____
trypsin cleaves bonds following arginine or lysine
chymotrypsin cleaves _____
chymotrypsin cleaves bonds following aromatic amino acids
elastase cleaves ____
elastase cleaves bonds after amino acids that have smaller, hydrophobic side chains
carboxypeptidases and aminopeptidases cleave ____
carboxypeptidases and aminopeptidases cleave bonds working from either end of peptides with little specificity
pepsinogen to pepsin
cleave 44 amino acid masking sequence to transform to active form - sel-activated process called autocatalysis - triggered by low pH of gastric juice
can also self-inactivate
GERD
heartburn - over-active proton pump (K+/H+ pump) - gastrin and histamine bind to receptors on parietal cell –> activation of protein kinase A –> phosphorylates pump leading to more acid in the stomach and low pH)
GERD treatments
- anatacids absorb protons (TUMS - calcium carbonate)
- inhibit histamine H2 receptor
- PPIs (proton pump inhibitors): bind directly to pump
amino groups eventually secreted in the form of _____ ; carbon skeletons converted into _____
amino groups eventually secreted in the form of urea; carbon skeletons converted into alpha-keto acids (can be oxidized for energy production or converted to glucose via gluconeogenesis)
transamination
amino groups from 17 amino acids (except glutamate, lysine, threonine) funnelled into glutamate - catalyzed by aminotransferase (pyridoxal phosphate)
- in cytosol
- amino acid + alpha ketoglutarate = alpha ketoacid + glutamate
- reverse rxn possible (depending on relative concentrations of substrates and products)
aminotransferases require ____ as a coenzyme
pyridoxal phosphate (derived from vitamin B6)
alanine aminotransferase
alanine + alpha ketoglutarate = pyruvate + glutamate
aspartate aminotransferase
aspartate + alpha ketoglutarate = oxaloacetate + glutamate
oxidative deamination
amino group from glutamate released as ammonium and alpha-ketoglutarate - catalyzed by glutamate dehydrogenase (in the mitochondria of the liver) - reversible
- removal of amino group + oxidation of glutamate (produce NADH or NADPH)
- in mitochondria
ammonium will be used to synthesize urea in the liver
ammonium vs ammonia
ammonium: odorless; most common form of free amino groups at physiological pH
- produced in the mitochondria from oxidative deamination; toxic if levels are too high so rapidly converted into urea within mitochondria to prevent spread and accumulation
ammonia: strong smell; used as cleaning agent
ammonium conversion to urea in tissues other than liver (urea synthesis only in liver)
two ways:
- most tissues: free ammonium incorporated into GLUTAMINE by GLUTAMINE SYNTHESTASE - glutamine can get out of cells, enters bloodstream, transported to liver - GLUTAMINASE in mitochondria of liver uses water to cleave ammonium off of glutamine – ammonium released converted to urea; glutamate can be can be acted upon by glutamate dehydrogenase to release a second amino group - keeps free ammonium levels in peripheral tissues low
- glucose-alanine cycle
glucose-alanine cycle
in muscle:
excess amino groups collected in teh form of glutamate –> transfers them to pyruvate, which then becomes alanine (transamination reaction by alanine aminotransferase) –> alanine takes amino groups to liver through blood, where alanine transferase converts it back to pyruvate and gives amino groups back to alpha-ketoglutarate to form glutamate –> glutamate is acted upon by glutamate dehydrogenase to rpoduce ammonium, which will become urea
- pyruvate released from this reaction enters gluconeogenesis to produce glucose which goes back to muscle and gets metabolized to pyruvate and enters this cycle again
carrier of ammonium from peripheral tissues to liver
glutamine
- free ammonium incorporated into glutamine by glutamine synthetase
- glutaminase in liver mitochondria cleaves ammonium off using water - glutamine gets converted back to glutamate and is acted upon by glutamate dehydrogenase to release another amino group
- glutamate + ammonium = glutamine
precursors for urea
NH4+, CO2, aspartate
carbamoyl phosphate synthetase 1 obligate allosteric activator
N-Acetylglutamate (synthesized from glutamate and acetyl CoA by N-acetylglutamate synthase)
- stimulated by arginine and glutamate
glutamate provides amino groups used in urea synthesis in two ways
- free ammonium is cleaved off of glutamate by glutamate dehydrogenase to form free ammonium which is used to form carbamoyl phosphate
- glutamate transfers its amino groups to oxaloacetate to form aspartate, which is used later to add the second amino group onto urea
three cytosolic enzymes of part two of urea synthesis
argininosuccinate synthetase, argininosuccinase, and arginase (clustered together in a complex)
urea cycle’s links to citric acid cycle
fumarate and aspartate
energy cost of urea cycle
3 ATP (4 high energy bonds) per urea molecule
overall rxn urea cycle
Aspartate + NH4+ + CO2 + 3 ATP → urea + fumarate + 2 ADP + AMP + 2Pi + PPi
Ammoniotelic
Organisms that eliminate excess nitrogen as ammonium rather than urea (ureotelic)
