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Transcript
26,5 Catabolismof Amino Acids
Nitrogen
795
balance
Normal adults generally maintain a nitrogen balance-the quantity of
nitrogen excreteddaily equals the intake. About B0% of the nitrogen
excretedin the urine is in the form of urea, and almost all the body'swaste
nitrogen of metabolism is excretedin the urine; the nitrogen compounds
in the feces come mainly from indigestible materials. Children have a
positive nitrogen balance-rhe excretion of lessnitrogen than is consumed.The nitrogen balance is positive becausechildren are growing and
their cells are making new proteins and other nitrogen compounds. Several conditions result in a negative nitrogen balance-the excretion of
more nitrogen than is consumed.During starvation and certain diseases,
the carbon skeleton of amino acids derived from the breakdor,rmof muscle proteins must be catabolized as an energy source. Since no new protein is available to eat, starving people excretemore nitrogen than they
consume.The lack of even one essentialamino acid in the diet resultsin a
negative nitrogen balance. With an essential amino acid missing, the
other amino acids cannot be used to make complete proteins.Theseother
amino acids are deaminated, and the nitrogen is excretedas urea.
26.5Cotobolismof smino ocids
AIMS: To distinguish betweenglucogenicond ketogenicomino
scids. To discusshow omino ocids con be usedfor energy
production,gluconeogenesis,
and the synthesisof fots.
Focus
The carbon skeletons of amino
acids are converted to intermediates of glucose metabolism
and fatty acid metabolism.
Once u-ketoacidshave been formed from amino acid by transamination
reactions, their carbon skeletons are subjected to further chemical
changes.One set of amino acids is converted to pyruvate, oxaloacetate,or
cr-ketoglutarate(Fig. 26.4).Amino acids that are conuertedto theseintermediates are called glucogenic, since thesecompounds are also important to
glucosemetabolism. Pyruvate,formed at the end of glycolysis,and oxaloacetate are intermediates of the citric acid cycle.The remainder of the amino
acids are converted to acetyl CoA, which is also a product of fatty acid
metabolism. The amino acids that are conuerted to acetyl CoA are called
ketogenic.
The conversion of all the amino acids to intermediates of glucose or
fatty acid metabolism demonstrates the highly organized character of
metabolism and the economy of nature. By using a single, central pathway
for the metabolism of sugars, fats, and amino acids, the cell greatly
decreasesthe number of enzymes and chemical steps that otherwise might
be required to accomplishthe sametask.
Cells have priorities for the utilization of amino acids present in the
amino acid pool. In a normal individual, well nourished with carbohydrates, fats, and proteins, the s1'nthesisof nonessential amino acids, proteins, and other nitrogen-containing compounds is at the top of the prior-
796
CHAPTER
26 Metabolismof NitrogenCompounds
Gliie
'
I
Y
oo
iltl
cH3-c- c\
oPyruvate
I
v
o
tl
CHr-C-S-eoA
Acetyl CoA
,ffi*ur"u
oo
iltl
-cu"- C - C H 2 - C - S - C o A
Acetoacetyl CoA
Ketone
bodies
Fatty
acids
oo
illt
c-c..
,c-cHr_eJJlc-Ketoglutarate
Figure26.4
Amino acidsare degraded
to pyruvate,acetyl CoA,or
intermediatesof the citric
acid cycle.
q"
tt----:----.*"*,o"1---.--------------@
ity list. Energy production comes second. The body does not store amino
acids as such. Any amino acids that remain after synthetic and energy
needs are met are converted to glucose and fatty acids.
:.r,, PRACTTCE
EXERCTSE
26.5
=
Explain how transamination provides the link between amino acid
metabolism and glucose metabolism or fat metabolism.
Energyproducdon
The carbons of amino acids are used for energy production when needed.
Upon demand, pyruvate and acetyl CoA derivgd from amino acids are oxi-
26.6 Synthesisof Amino Acids
797
dized to carbon dioxide in the citric acid cycle. Moreover, by forming
oxaloacetate and a-ketoglutarate from glucogenic amino acids, cells can
replenish or increase the concentrations of intermediates of the citric acid
cycle. An increase in these intermediates enables cells to step up energy
production. You may recall that oxaloacetate for the citric acid cycle can
come from severalplaces in metabolism. We have seen that the carboxylation of pyruvatein gluconeogenesisis one of those places.Nowwe seethat
amino acid metabolism is another.
Certain emergenciessuch as diabetes or starvation result in a reduction
in the amount of aceryl CoA in the liver. Liver cells respond by using acetyl
CoA produced in amino acid metabolism to make ketone bodies. The
ketone bodies are transported to other tissues,where they are oxidized for
energy production.
Slmthesis
of glycogen
and triglycerides
From our study of glucose metabolism, we know that glucose is formed
from pyruvate by gluconeogenesis,in which oxaloacetateis an intermediate (seeSec.24.8).The cell does not recognizewhether the pyruvate has
come from glucose or from amino acid metabolism. Once glucose has
been synthesized,it can be assembledinto glycogenand stored in muscle
or liver cells. Oxaloacetatefrom amino acid metabolism also can be converted to glucosein gluconeogenesis.
Fatty acids, as we have seen, are synthesized from acetyl CoA.
The acetyl CoA can come from glucose metabolism, from fatty acid
metabolism, or from amino acid metabolism. Newly synthesized fatty
acids are either used immediately for energy production or converted to
triglycerides or membrane lipids. The triglycerides are stored in adipose
tissue as an energy reserve. Humans cannot synthesize glucose from
acetyl CoA, since people lack the enzyme that converts acetyl CoA to
pyruvate.
26.6 Synthesis
of omino acids
AIM: Toshow the relotionship betweenthe citric ocid cycleond
the synthesisof nonessentiol
omino ocids.
Synthesis of 7 of the 12
nonessential amino acids is
simple.
Most animal proteins have a
higher nutritional value than
vegetable proteins becausethey
have more essentialamino acids.
Our bodies need to synthesizenonessential amino acids (see Sec.21.6)
becausetheir proportions in our diet seldom match our bodies' needs.The
main starting materials for this synthesis are pyruvate and two intermediates of the citric acid cycle: o-ketoglutarate and oxaloacetate.As we have
seen, cr-ketoglutarateaccepts amino groups from other amino acids in
transamination to give glutamic acid, and arginine is formed in the urea
cycle. TWo other nonessential amino acids-aspartic acid and alaninemay be synthesized directly from cr-ketoacidsbecause the reactions catalyzed by the transaminases are reversible. Reversalsof transamination
reactions form alanine from pyruvic acid and aspartic acid from