The Krebs cycle itself actually begins when
acetyl-CoA combines with a four-carbon molecule
called OAA (oxaloacetate) (see Figure above). This produces citric acid, which has six carbonatoms. This is why the Krebs cycle is also called the citric acid cycle.
How is oxaloacetate produced?
The beginning of this process takes place in the mitochondrial matrix, where pyruvate molecules are found.
A pyruvate molecule is carboxylated by a pyruvate carboxylase enzyme, activated by a molecule each of ATP and water
. This reaction results in the formation of oxaloacetate.
Is oxaloacetate regenerated in the Krebs cycle?
Oxaloacetate is regenerated in the last step of the TCA cycle
. Malate is dehydrogenated to produce oxaloacetate. Enzyme malate dehydrogenase catalyses this reaction.
What happens to oxaloacetate in the Krebs cycle?
The citric acid cycle (also called the Krebs cycle and the tricarboxylic acid cycle). In the citric acid cycle, initially
each acetyl CoA molecule is condensed with oxaloacetic acid to form the 6-C citric acid
. For every acetyl CoA entering entering the cycle: 3 molecules of NADH are generated.
How does oxaloacetate enter gluconeogenesis?
Gluconeogenesis begins in the mitochondria with the formation of oxaloacetate
by the carboxylation of pyruvate
. This reaction also requires one molecule of ATP, and is catalyzed by pyruvate carboxylase.
How is pyruvate converted to oxaloacetate?
Pyruvate carboxylase
is found on the mitochondria and converts pyruvate into oxaloacetate. Because oxaloacetate cannot pass through the mitochondria membranes it must be first converted into malate by malate dehydrogenase.
What metabolites can be used to produce oxaloacetate?
The most important anaplerotic pathways are carbon dioxide fixation by either pyruvate carboxylase or PEP carboxylase, leading to the formation of oxaloacetate (Fig. 2.10). Pyruvate carboxylase is activated at a high ATP/ADP ratio and by
acetyl-CoA
and is inhibited by L-aspartate.
How is oxaloacetate replenished?
One important way by which human cells and other mammalian cells replenish the intermediates is by replenishing oxaloacetate; this is done by
carboxylating pyruvate into oxaloacetate via a process that is catalyzed by an enzyme called pyruvate carboxylase
.
Why is oxaloacetate important in the citric acid cycle?
How is oxaloacetate converted to aspartate?
To complete the shuttle, oxaloacetate must be transported from the matrix to the cytoplasm but there is no such transport system. Instead, oxaloacetate is
first converted to aspartate by aspartate aminotransferase (Chapter 17) and then transported out of the mitochondria via the glutamate-aspartate translocase
.
How is oxaloacetate regulated?
The regulation of the supply of oxaloacetate (OAA) for mitochondrial metabolism
via phosphoenolpyruvate carboxylase (PEPC) by metabolites
is studied in barley (Hordeum vulgare L.) leaf protoplasts in light or darkness as well as under photorespiratory or non-photorespiratory conditions.
How can the cycle continue to function if insufficient oxaloacetate is present?
TRICARBOXYLIC ACID CYCLE
If oxaloacetate is removed from the cycle for glucose synthesis, it must be replaced, since
if there is not enough oxaloacetate available to form citrate, the rate of acetyl CoA metabolism, and hence the rate of formation of ATP, will slow down
.
Which mineral helps convert pyruvate to oxaloacetate in the TCA cycle?
Pyruvate carboxylase (PC) is a biotin-containing enzyme that catalyses the
HCO
3
−
– and MgATP
-dependent carboxylation of pyruvate to form oxaloacetate.
Which enzyme converts pyruvate to oxaloacetate?
Pyruvate carboxylase (PC)
is a biotin-bound mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate when abundant acetyl CoA is available, replenishing Krebs cycle intermediates in the mitochondrial matrix.
What reaction is catalyzed by pyruvate decarboxylase?
Pyruvate decarboxylase is an enzyme (EC 4.1. 1.1) that catalyses the
decarboxylation of pyruvic acid to acetaldehyde
.
What is mitochondrial oxaloacetate?
Oxaloacetate,
an intermediate in the tricarboxylic acid cycle
, plays important roles in regulating mitochondrial function, gluconeogenesis, the urea cycle, and amino acid syntheses.
What amino acids are made from oxaloacetate?
The oxaloacetate/aspartate family of amino acids is composed of
lysine, asparagine, methionine, threonine, and isoleucine
. Aspartate can be converted into lysine, asparagine, methionine and threonine. Threonine also gives rise to isoleucine.
Where is oxaloacetate found in the cell?
Oxalacetic acid can be found primarily in
cellular cytoplasm
, cerebrospinal fluid (CSF), and urine, as well as in human liver tissue. Oxaloacetate forms in several ways in nature. A principal route is upon oxidation of malate, catalyzed by malate dehydrogenase, in the citric acid cycle (see Figure 1 above).
How is oxaloacetate depleted?
Depletion of glucose and oxaloacetate can be triggered by
fasting, vigorous exercise, high-fat diets or other medical conditions
, all of which enhance ketone production. Deaminated amino acids that are ketogenic, such as leucine, also feed TCA cycle, forming acetoacetate & ACoA and thereby produce ketones.
