1. Copyright © 2006 by Elsevier, Inc. 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)

2. Copyright © 2006 by Elsevier, Inc. Removing the amino group; deamination Basically, a-ketoglutarate takes the NH4+ from an amino acid  -ketoglutarate glutamate alaninepyruvate C C C C C O OH O O O-O- C C C C C O OH NH 2 O O-O- NH 4 + Transaminase (aminotransferase)

3. Copyright © 2006 by Elsevier, Inc. 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 + + H 2 O NADH + H + + NH 3 +  -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.

4. Copyright © 2006 by Elsevier, Inc. 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 NH 4 + is toxic in part because it depletes  -ketoglutarate, thus halting the TCA cycle.

5. Copyright © 2006 by Elsevier, Inc. Main Urea Cycle Steps The ammonia from deaminiation This ammonia comes from “step 2”, i.e. the conversion of glutamate back to  -ketoglutarate, which is tied directly to the running of the TCA cycle.

6. Copyright © 2006 by Elsevier, Inc. 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

7. Copyright © 2006 by Elsevier, Inc. What would be the ATP output of the breakdown of isoleucine? (Isoleucine is converted into succinyl-CoA after deamination)

8. Copyright © 2006 by Elsevier, Inc. Figure 25.4b