Amino Acid Nitrogen And Urea Cycle Flashcards
Amino acid functions
. Protein synthesis
. Precursors for synthesis of specialized N-containing compounds
T/F there is long-term amino acid storage in body
F
Sources of amino acids
. Synthesis of nonessential amino acids
. Digestion and absorption of dietary protein
. Degradation (turnover) of body proteins
T/F most adults are in net nitrogen balance (N in = N out)
T
How do amino acids enter body pool?
. Cellular synthesis of nonessential amino acids
. Directions and absorption of dietary amino acids
. Degradation of body proteins
How are nonessential amino acids synthesized?
. Metabolism intermediates formed during glycolysis and TCA cycle
Essential amino acids
. Phe . Val . Thr . Trip . Ile . Met . His . Arg . Leu . Lys
Nonessential amino acids
. Ser . Gly . Cys . Ala . Asp . Asn . Glu . Gln . Pro . Tyr
Synthesis of Tyr from Phe
. Hydroxylation of Phe from diet via phenylalanine hydroxylase (PAH)
. Dependent on tetrahydrobiopterin (BH4)
. Rxn first step in catabolism of phe that forms fumarate and acetoacetate
What metabolic intermediate makes Ser
3-phosphoglycerate from glycolysis
. Gly and Cys made from Ser
What metabolic intermediate can form Ala
Pyruvate
What metabolic intermediate can form Aspartate?
Oxaloacetate
. Aspartate then can form asparagine
Aminotransferase enzymes
. Catalyze trans am inaction of alpha-Ketoacid intermediates to form Ala, Glu, and Asp
. Depends on vit. B6 (pyridoxal phosphate) for transfer of amino group
Amidation fo Aspartate
. Glutamine is nitrogen donor
. Done via Asparagine synthetase
. Needs ATP
. Forms asparagine
Amidation of glutamate
.done via glutamine synthetase
. Needs ATP
. Forms glutamine
. Ammonia is nitrogen donor
Synthesis of Pro and Arg from Glu
. Deamidation of Gln to Glu via glutaminase
. Glu then turns into Pro and Ornithine
. Ornithine turns into citrulline which then undergoes steps to form Arg
Synthesis of Ser, Gly, and Cys from 3-phosphoglycerate
. 3-PG turns into Ser
. Ser dependent on THF and Vit. B6 forms Gly
. Ser dependent on Vit. B6 and homocysteine form cystathionine that forms Cys dependent on vit. B6 again
Mechanism for transport of toxins ammonia w/in body
. Glu Gln conversation by glutamine synthetase/glutaminase
Formation of homocysteine
. Formed during catabolism of Met
Absorption of dietary protein in stomach
. HCL denatures proteins
. Pepsinogen is secreted, undergoes conformational change from low pH autoactivation via limited proteolytic to form active pepsin
. Pepsin further activates other pepsinogen
. Initiates breakdown of dietary protein to shorter polypeptides
Digestion of dietary protein in small intestine
. Pancreatic enzymes activated via limited proteolysis initiated by enteropeptidase
. Each activated enzyme hydrolyzes specific peptide bonds of chains making oligopeptides
. Oligopeptides degraded to free amino acids via aminopeptidases in brush border
Enteropeptidase
. Extracellular enzyme on luminal surface of intestinal epithelial cells
. Activates trypsinogen to trypsin
. Trypsin activates more trypsinogen and other zymogens
Trypsin action
. Hydrolyzes internal peptide bonds where carboxylase group is provided by Arg or Lys
Absorption of amino acids from small intestine
. Free amino acids and some di and tri-peptides absorbed
. Specific transporters on intestinal epithelial cell surface
. Di and tri-peptides absorbed and then hydrolyzed to free amino acids w/in cell
. Only free amino acids released into portal circulation
Lab evaluation of exocrine pancreatic function
. Pancreatic elastase measured through fecal elastase
. Presence of this means exocrine dysfunction
Degradation of body proteins
. Daily turnover of 300-400g protein
. Degraded via proteases in lysosome (ATP-independent) or via ubiquitin-proteasome system in cytosol (ATP-dependent)
. Amino acids enter body pool for utilization
Removal of amino acid N from Glu
. Glu undergoes oxidative deamination to make Ketoglutarate and ammonia
. Done via glutamate dehydrogenase (GDH)
. Needs NADPH
. Reaction can go both ways
Other than Glu, what are other sources of ammonia
. Bacterial breakdown of urea in intestine
Role of Ala and Glu in transporting amino acid N to liver
. N removed during aminoa acid catabolism in peripheral tissues is brought to liver for detoxification
. Ala and Glu transport N from skeletal muscle
What is major extrahepatic site for amino acid catabolism?
Skeletal muscle
Besides transporting N, what else does Ala deliver to liver?
Carbon atoms for hepatic gluconeogenesis
Detoxification of amino acid N in liver
. Done via urea cycle or Glu synthesis in perivenous hepatocytes
Percentage of N detoxified through urea synthesis?
90%
Number of reactions in urea cycle
5
Urea cycle
. Low-affinity high capacity mechanism
. Found in periportal hepatocytes
. N from ammonia or Asp and carbon from bicarbonate are incorporated into urea
. ATP-dependent
. Irreversible
. Complete cycle only completed in liver (some reactions w/in cycle can be done in other tissues)
. Net rxn: NH4 + Asp + 3ATP + H2O -> Urea + Fumarate = 2ADP + AMP + 2Pi + 2 PPi
. Overall NH4 + Asp + 3ATP -> urea
Where is glutamine transported to release ammonia?
From liver to kidney
PH regulation w/ urea cycle during acidosis
. Drop in pH inhibits periportal urea synthesis via dec. transport of Glu into hepatocytes and inhibition of glutaminase
. Inc. in perivenous synthesis of Glu to prevent hyperammonemia
. Inhibition of urea cycle preserve bicarbonate
PH regulation during alkalosis by urea cycle
. Urea synthesis inc. and Glu synthesis dec. causing inc. consumption of bicarbonate