Download 26,6 Synthesis of omino ocids

26.6 Synthesisof Amino Acids
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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.
Certainemergenciessuch as diabetesor starvationresult in a reduction
in the amount of acetyl 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
energyproduction.
S5mthesis of glycogen
and triglycerldes
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 ocids
AIM: Toshow the relotionship betweenthe citric ocid cycleond
the synthesisof nonessentialomino ocids.
Slmthesis of 7 of the 12
nonessential amino acids is
simple.
Most animal proteins have a
higher nutritional value than
vegetableproteins 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 qmthesis are pyruvate and two intermediates of the citric acid cycle: a-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 qmthesized directly from cr-ketoacidsbecausethe reactions catalyzed by the transaminases are reversible. Reversalsof transamination
reactions form alanine from pyruvic acid and aspartic acid from
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CHAPTER
26 Metabolismof NitrogenCompounds
oxaloacetic acid.
oo
iltl
o
II
+ Glutamic acid ;---- CH3CH-C-OH
CH3-C-C-OH
* a-Ketoglutarate
I
NHz
Pyruvic acid
o
il
oo
illl
Alanine
+ Glutamic acid ;-
HO-C-CH2-C-C-OH
oo
il
+ d-Ketoglutarate
HO-C-CH2CH-C-OH
I
NH,
Asparticacid
Oxaloacetic
acid
Glutamineand asparagineareformed from glutamic acid and aspartic acid
by reaction of the side-chain carboxyl groups with ammonia.
oooo
ilililil
HO-C-CH2CH-C-OH
rl
+ NH3 -------HzN-C-CH2CH-C-OH
NHz
NHz
Aspartic acid
o
Asparagine
o
HO-C-CH2CH2CH-C-OH
+ HzO
o
+ NH3 +
o
II
+ H2O
HrN-C-CH2CH2CH-C-OH
I
NHz
NHz
Glutamicacid
Glutamine
Tyrosine,the only nonessential amino acid with an aromatic side chain, is
produced from the essential amino acid phenylalanine. The conversion
requires a single oxidation step catalyzed by the enzyme phenylalanine
hydroxylase.
Phenylalanine
(
}.crt
\\//t-"\\//l
-cu-co2H -!try:
to{
fcu,-ctt-co2H
NH,
Phenylalanine
NH,
Tyrosine
So far we have seen how 7 of the 12 nonessential amino acids are synthesized. The syntheses of the remaining S-cysteine, histidine, glycine,
proline, and serine-are more complex. Their synthesiswill not be considered here.The qmtheses of 4 of the nonessential amino acids from oxaloacetate and a-ketoglutarate, two intermediates in the citric acid cycle,
demonstrate an important metabolic principle: Besidesbeing a pathway of
catabolism, the citric acid rycle is a pathway of anabolism-a metabolic
switch-hitter.