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Amino Acid Transport and Storage. ionized AA’s circulate in the plasma, ~ 35-65 mg/dl control is not known, but even after a meal, plasma levels return to normal very rapidly also, when plasma [AA] decreases, cell protein catabolism compensates transport of AA’s into cells is carrier-mediated
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Amino Acid Transport and Storage • ionized AA’s circulate in the plasma, ~ 35-65 mg/dl • control is not known, but even after a meal, plasma levels return to normal very rapidly • also, when plasma [AA] decreases, cell protein catabolism compensates • transport of AA’s into cells is carrier-mediated • very little free AA’s in cells, rapidly used for proteins • proteins in different tissue cells are linked via reversible exchange with plasma amino acids • plasma proteins (e.g. albumin) are another important AA source (degraded by tissue macrophages and AA’s released)
NH2 O O O O O C C C C C C C C C C OH O- OH O- Removing the amino group; deamination Basically, a-ketoglutarate takes the NH4+ from an amino acid -ketoglutarate glutamate NH4+ Transaminase (aminotransferase) alanine pyruvate
Continuing the amino acid breakdown • The first step in this example was turning the AA alanine into pyruvate • This involved production of glutamate (i.e. glutamic acid) • The second step is breakdown of glutamate glutamate + NAD+ + H2O NADH + H+ + NH3 + -ketoglutarate • NOTE: This rxn needs NAD+, which is high in a low-energy state.So, energy is low and we catabolize proteins for energy. Glutamate breakdown yields NADH; plus, the pyruvate from step one also can be used for energy. We also generated -ketoglutarate.
Fate of the ammonia, role of urea • The ammonia generated from the breakdown of glutamate can go towards generating other AA’s, or • The ammonia can be excreted • excretion occurs mainly as urea (2 ammonia molecules plus a carbon dioxide) • urea formation occurs essentially only in the liver • Excess free NH4+ is toxic in part because it depletes -ketoglutarate, thus halting the TCA cycle.
Main Urea Cycle Steps The ammonia from deaminiation This ammonia comes from “step 2”, i.e. the conversion of glutamate back to a-ketoglutarate, which is tied directly to the running of the TCA cycle.
Strategy of Amino Acid Degradation • AA degradation occurs in the liver, mainly with protein excess. • note, this is not protein breakdown per se • Goal is to form major metabolic intermediates that can be converted into glucose or be oxidized by the TCA cycle • AA’s that are degraded to Acetyl CoA or acetoacetyl CoA are ketogenic because they give rise to ketone bodies • AA’s that form glucose or progress through the TCA cycle are termed glucogenic
What would be the ATP output of the breakdown of isoleucine? (Isoleucine is converted into succinyl-CoA after deamination)