Transcript Introduction to Physiology: The Cell and General Physiology

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)
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Removing the amino group; deamination
Basically, a-ketoglutarate takes the NH4+ from an
amino acid
O
O
O
O
OH
O-
C C C C C
O-
-ketoglutarate
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O
C C C C C
OH
glutamate
NH4+
alanine
NH2
Transaminase (aminotransferase)
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.
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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.
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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.
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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
Copyright © 2006 by Elsevier, Inc.
• What would be the ATP output of the
breakdown of isoleucine? (Isoleucine is
converted into succinyl-CoA after
deamination)
Copyright © 2006 by Elsevier, Inc.
Copyright © 2006 by Elsevier, Inc.
Figure 25.4b