Chapter 17: Citric Acid Cycle Flashcards
is a central pathway for recovering energy from several metabolic fuels, including
carbohydrates, fatty acids, and amino acids, that are broken down to acetyl-CoA for oxidation.
citric acid cycle
what does the citric acid cycle oxidize
acetyl-CoA to two molecules of CO2
what does the citric acid cycle oxidizes in a manner that conserves what
liberated free energy in
the reduced compounds NADH and FADH2
The cycle is named after the
product of its first reaction
citrate
One complete round of the citric acid cycle yields
two molecules of CO2
three NADH
one FADH2
GTP or ATP
is consumed in the first step of the citric acid cycle is regenerated in the last step of the cycle.
oxaloacetate
the citric acid cycle acts as a multistep catalyst that can what
oxidize an unlimited number of acetyl groups
In eukaryotes, all the enzymes of the citric acid cycle are located in the
mitochondria
all substrates, including what must be generated in the mitochondria or be
transported into mitochondria from the cytosol.
NAD+ and GDP
all the products of the citric acid cycle must be consumed where and transported where
mitochondria
cytosol.
however, the net effect of each round of the cycle is
the oxidation of
one acetyl group to 2 CO2.
Acetyl-CoAis formed from pyruvate through oxidative decarboxylation by a
multienzyme complex named
pyruvate dehydrogenase
This complex contains multiple
copies of three enzymes
pyruvate dehydrogenase (E1)
dihydrolipoyl transacetylase
(E2)
dihydrolipoyl dehydrogenase (E3)
Decarboxylates pyruvate yielding a hydroxyethyl-tpp carbanion
Thiamine pyrophosphate (tpp)
What are advantages of multienzymes:
- The distance that substrates must diffuse between active sites is minimized, thereby
enhancing the reaction rate. - The channeling of metabolic intermediates between successive enzymes in a
metabolic pathway reduces the opportunity for these intermediates to react with other molecules, thereby minimizing side reactions. - The reactions catalyzed by a multienzyme complex can be coordinately controlled.
Accepts the hydroxyethyl carbanion from TPP as an acetyl group
Lipoic acid
Accepts the acetyl group from lipoamide
Coenzyme A (CoA)
Reduced by lipoamide
Flavin adenine
Reduced by FADH2
Nicotinamide adenine dinucleotide (NAD+)
acts as a swinging arm
lipoamide
what does lipoamide do
swings disulfide group from E1 (where it picks up a hydroxyethyl group)
to the E2 active site (where the
hydroxyethyl group is transferred to form acetyl-CoA)
to E3 (where the reduced disulfide is reoxidized)
are toxic because they bind to sulfhydryl compounds (including lipoamide) that can form bidentate adducts.
arsenite and organic arsenicals
The inactivation of lipoamide-containing enzymes by what
arsenite
brings respiration to a halt
pyruvate dehydrogenase
This differential toxicity is the basis for the early twentieth century use of organic arsenicals in the treatment of
syphilis
Aconitase contains a
[4Fe–4S] iron–sulfur cluster
that presumably coordinates the OH group of citrate to facilitate its elimination
[4Fe–4S] iron–sulfur cluster
normally participate in redox
processes
Iron–sulfur clusters
The α-ketoglutarate dehydrogenase reaction chemically resembles the reaction catalyzed by
pyruvate dehydrogenase multienzyme complex
is the only membrane-bound enzyme of the citric acid
cycle
Succinate dehydrogenase
catalyzes the stereospecific dehydrogenation of succinate to fumarate
Succinate dehydrogenase
In eukaryotes, the products of the pyruvate dehydrogenase reaction, NADH and acetyl-CoA, also activate the
pyruvate dehydrogenase kinase
the hormone that signals
fuel abundance
Insulin
reverses the inactivation by activating pyruvate dehydrogenase phosphatase,
which removes the phosphate groups from pyruvate dehydrogenase.
Insulin
The citric acid cycle’s flux is controlled primarily by three simple mechanisms:
(1) substrate
availability
(2) product inhibition
(3) competitive feedback inhibition by intermediates further along the cycle.
Perhaps the most crucial regulators of the citric acid cycle are
its substrates acetyl-CoA
and oxaloacetate,
and NADH
Since the citric acid cycle is a cyclical pathway, any of its
intermediates can be converted to oxaloacetate and used for gluconeogenesis.
Gluconeogenesis
is a cytosolic process that requires acetyl-CoA. Acetyl-CoA is generated in the mitochondrion but transported across the mitochondrial membrane as
citrate
Fatty acid biosynthesis
An increase in the concentrations of citric
acid cycle intermediates supports increased
flux of
acetyl groups through the cycle
Pyruvate carboxylase― senses the need for more citric acid cycle intermediates through
its activator
acetyl-CoA
subsists largely on lipids, using the citric acid cycle to produce precursors for amino acid synthesis and using the glyoxylate cycle to produce
carbohydrate precursors.
glyoxylate cycle
also stimulates cell growth and differentiation by increasing the synthesis of glycogen,
proteins, and triacylglycerols.
Insulin
Muscle cells and adipocytes express an insulin-sensitive glucose transporter known as
GLUT4.
inhibits transcription of the
genes encoding the gluconeogenic enzymes PEP
carboxykinase, fructose-1,6-bisphosphatase, and
glucose-6-phosphatase and stimulates transcription
of the genes for the glycolytic enzymes glucokinase
and pyruvate kinase.
Insulin
Most of the brain’s energy
production powers the
plasma membrane
which maintains the membrane potential
required for nerve impulse transmission.
plasma membrane
is the brain’s primary fuel.
glucose
blood glucose concentration of less than half the normal
value of what results in brain dysfunction.
~5 mM
