urea cycle: averting NH3 toxicity Flashcards
excess nitrogen is constantly…
excreted from animals in a variety of metabolic forms
fish are…
ammonotelic (ie NH3-excreting)
birds are…
uricotelic(ie uric acid excreting)
mammals are…
ureotelic (ie urea-excreting); primarily make urea but some creatinine and uric acid; amount excreted varies; some of us make too much uric acid (gout)
where do the first two reactions of the urea cycle occur?
within the mitochondrial matrix
where do the last three steps of the cycle occur?
cytosol, which is the cell’s aq phase
what is transported back to the mitochondrial matrix?
ornithine
_____ is exported from the liver, entering circulation for uptake and excretion by the kidney
urea
Urea Transporters A and B
UT-A- exports urea from liver
UT-B- imports urea into kidney
what enzyme reactions in the urea cycle do you need to know? (draw them)
ornithine transcarbamoylase (mitochondria), argininosuccinate synthase (cytoplasm), argininosuccinate lyase (cytoplasm), and arginase (cytoplasm)
what do you absolutely need to know and draw out?
THE UREA CYCLE
what induces synthesis of urea cycle enzymes?
high protein diet
glucagon
pancreatic a-cell hormone that stimulates glucose synthesis as well as biosynthesis of urea cycle enzymes; certain AAs stimulate glucagon release and casein (main milk protein) is rich in those AAs; by reducing NH3, glucagon increases levels of a-keto-acids needed for glucose synthesis
indirect activation of urea cycle by glutamate and arginine
digestion of protein foodstuffs increases liver AA content, and transamination to a-KG increases liver glutamate levels; bc arginine undergoes little/no transamination, digestion of protein foodstuffs greatly increases liver arginine concentration; consequently, high levels of Gly & Arg trigger the synthesis of N-acetyl-glutamate, an essential activator of CPS-I, meaning that CPS-I is totally inactive in absence of N-acetyl-glutamate
N-acetyl-glutamate synthase
Glutamate+ Acetyl-CoA ->< N-Acetyl-Glutamate +CoA
