Week 11: Gluconeogenesis, Pyruvate Dehydrogenase Complex, Citric Acid Cycle Flashcards
The reduced form of _____ is an indirect source of high-energy compounds.
NADH
Lipoic acid is associated with dihydrolipoyl transacetylase. It accepts a _______ from hydroxyethyl TPP, oxidizing the group to an _____. It delivers this _____ to coenzyme A. It then is oxidized by NAD+, so it acts as a _____ agent.
hydroxyethyl group, acetyl
acetyl group
reducing
A condensation reaction is one in which a new ______ is formed. The reaction of ______ and ______ to form citrate involves the formation of such a ______.
carbon-carbon bond
acetyl-CoA, oxaloacetate
C-C bond
What type of reaction is catalyzed by isocitrate dehydrogenase and α-ketoglutarate dehydrogenase?
An oxidative decarboxylation
Both dehydrogenases are involved in redox reactions in which a CO2 is abstracted from a substrate. In both cases NAD+ is reduced while the other substrate is oxidized. Thus, both of these enzymes catalyze oxidative decarboxylations.
The reactions that act as control points in the citric acid cycle are those that have the most ______ in the cycle, i.e. these are the most ____ reactions. These control points are allosterically regulated by ATP and NADH. Other regulators also allosterically regulate each of the enzymes catalyzing these reactions.
_______ and ________ are some examples of enzymes that catalyze control point reactions in the citric acid cycle.
negative free energy changes, favorable
Isocitrate dehydrogenase, α-ketoglutarate dehydrogenase
______ and _____ inhibit all four of the enzymes that are the ________ in the citric acid cycle. Succinyl-CoA inhibits two of the control points, citrate synthase and α-ketoglutarate dehydrogenase.
Acetyl-CoA inhibits pyruvate dehydrogenase. Citrate inhibits citrate synthase. ADP and NAD+ stimulate isocitrate dehydrogenase.
ATP and NADH, control points
The reactions of glycolysis occur in the ______ of the cell. The citric acid cycle, which is found only in _____, occurs in the _______.
cytoplasm
eukaryotes, mitochondrial matrix
How can the synthesis and breakdown of fructose-2,6-bisphosphate be controlled independently?
The concentration of fructose-2,6-bisphosphate synthesis depends on the balance between its synthesis and its breakdown. Its synthesis is catalyzed by _________ , while its breakdown is catalyzed by _________. Both of these enzymes are regulated by __________ mediated by kinases and phosphatases.
phosphofructokinase, fructose-1,6-bisphosphatase
phosphorylation and dephosphorylation
Fructose-2,6-bisphosphate is an allosteric effector in glycolysis and in gluconeogenesis.
In glycolysis, it activates ______ and is a ______ allosteric effector in the glycolysis pathway.
In gluconeogenesis, it inhibits _____.
phosphofructokinase
positive
fructose bisphosphate phosphatase
Most gluconeogenesis reactions take place in the _____, but there are some reactions that occur in the ______.
cytoplasm, mitochondria
When the body ______, carbohydrates are broken down via _____. When ______, glucose can be synthesized from the intermediates of the glycolytic and citric acid pathways by ______.
needs energy, glycolysis
energy is not needed, gluconeogenesis
Gluconeogenesis proceeds in reverse order from glycolysis, and many of the glycolysis enzymes also catalyze gluconeogenesis. However, at _____ points there are unique enzymes that catalyze only gluconeogenesis, making it a distinct pathway.
four points
Gluconeogenesis is NOT the only carbohydrate biosynthetic pathway.
Carbohydrates are synthesized by ______ in plants, by the gluconeogenesis process, and when glucose is used to synthesize other hexoses and hexose derivatives.
photosynthesis
If one were to introduce a pulse of acetyl CoA with the two carbons in acetyl CoA labeled with a radioactive tag, followed by unlabeled acetyl CoA, what would be the ultimate fate of the two carbons?
The carbonyl carbon from the acetyl CoA will be lost as CO2 during the second round, while the methyl carbon becomes incorporated in the core of the circulating compounds (e.g., the 2,3 positions of succinate and fumarate) and are only lost through dilution.
How many oxidation-reduction steps are found in one turn of the cycle?
Four
There are four steps: the isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase steps.
If one NADH generates 3 ATPs through oxidative phosphorylation and 1 FADH2 generates 2 ATPs through oxidative phosphorylation, how many ATPs can be generated from the products of one cycle through the TCA pathway?
Twelve ATPs can be generated: 9 from the 3 NADHs, 2 from the FADH2, and 1 directly generated by the combination of succinyl-CoA synthetase and nucleoside diphosphate kinase (reaction 5).
Gluconeogenesis:
- The synthesis of ____ from _____.
- The major site of gluconeogenesis is the ____,
although gluconeogenesis can occur in the ____. - Gluconeogenesis is especially important during
_____, as glucose is the primary fuel
for the brain and the only fuel for red blood cells.
glucose, pyruvate
liver, kidney
fasting or starvation
The beginning: The Conversion of Pyruvate into Phosphoenolpyruvate
* Requires two enzymes,
* First: ______ (in _____)
catalyzes formation of ______.
* Second: _____________ (in ______)
pyruvate carboxylase, mitochondria
oxaloacetate
phosphoenolpyruvate carboxykinase, cytoplasm
Pyruvate carboxylase requires the ______ as a cofactor.
* The formation of oxaloacetate by pyruvate carboxylase occurs in ____ stages.
vitamin biotin
three
The formation of oxaloacetate by pyruvate carboxylase occurs in the ______. (Step 1)
- Oxaloacetate is reduced to ____ and transported into the cytoplasm, where it is _____ to oxaloacetate with the generation of _______.
- PEP is then synthesized from oxaloacetate by
phosphoenolpyruvate carboxykinase. (Step 2)
mitochondria
malate, reoxidized
cytoplasmic NADH
Step 11: Glucose-6-Phosphatase
* Glucose 6-phosphate is transported into the lumen of the endoplasmic reticulum.
* Glucose 6-phosphatase, an ______ on the inner surface of the endoplasmic reticulum, catalyzes the formation of ______ from ______.
integral membrane
glucose, glucose 6-phosphate
What barrier prevents glycolysis from simply running in reverse to synthesize glucose?
How is this barrier overcome in gluconeogenesis?
3 irreversible steps of glycolysis (Steps 1, 3, 10)
4 new enzymes of gluconeogenesis.
Since G6P is a ______ effector for Hexokinase since…
G6P is a ____ effector for Glucose-6-phosphatase in glucogenesis
negative, build-up of G6P would stop hexokinase and halter glycolysis
positive
Lots of glucose, ATP needed –>
Glucose scarce and needed –>
Glycolysis
Gluconeogenesis
If cell needs energy, [AMP] ______, therefore AMP is a ______ effector of phosphofructokinase (PFK)
AMP is a _____ effector of fructose-1,6-biphosphate in gluconeogenesis
increases, positive
negative
If you have plenty of energy [ATP] ______, therefore ATP is a _____ effector of phosphofructokinase (PFK)
increases, negative
Higher [H+] means ____ pH.
H+ is a ____ effector of glycolysis to..
lower
negative, to keep enzymes from being damaged
Citrate is a ______ effector of glycolysis and a ______ effector of gluconeogenesis
negative, positive
In the liver, the rates of glycolysis and gluconeogenesis are
adjusted to maintain _______ levels.
- The key regulator of glucose metabolism in the liver is
_______. Fructose 2,6-bisphosphate _____ phosphofructokinase and ____ fructose 1,6-bisphosphatase. - The kinase that synthesizes fructose 2,6-bisphosphate
(phosphofructokinase 2) and the phosphatase that
hydrolyzes this molecule (fructose bisphosphatase 2) are
located on the same polypeptide chain. Such an
arrangement is called a ________.
blood-glucose
fructose 2,6-bisphosphate
stimulates, inhibits (positive affector for glycolysis, negative affector for gluconeogenesis)
bifunctional enzyme
Fructose 2,6-Biphosphate different names depending on the direction it is catalyzing.
_________ when adding a phosphate (glycolysis)
_________ when removing a phosphate (gluconeogenesis)
PFK-2, phosphofructokinase-2
FBPase2, Fructose biphosphatase
How does the enzyme know which domain should be active?
Synethesis and Degradation of Fructose 2,6-biphosphate is controlled by _________
Low blood glucose levels trigger pancreas to release the hormone ______.
Glucagon acts as a _____ in signal transduction pathway:
- Glucagon binds to a G-protein receptor
* The G-protein receptor activates adenylate cyclase
* Adenylate cyclase catalyzes formation of cyclic AMP
* CMP binds to protein kinase A and activates it
blood glucose sensitive hormones
glucagon
primary messenger
Alanine is a _____ effector of glycolysis
Acetyl CoA is a _____ effector of glucogeonegensis
negative
postive
What would be the effect on an organism’s ability to produce
glucose if there was an inability to produce adequate
quantities of pyruvate carboxylase?
Lack of pyruvate carboxylase would cause hypoglycemia.
Lactic acid could build up in the blood.
What would be the effect on an organism’s ability to use
glucose as an energy source if a mutation inactivated
glucose 6-phosphatase in the liver?
During the night, while fasting glucose levels would
drop to dangerously low levels.
The formation of acetyl CoA from pyruvate is ______ in animal cells.
* Acetyl CoA has two possible fates:
irreversible
metabolism by the citric acid cycle or incorporation into fatty acids.
The synthesis of acetyl CoA from pyruvate consists of three
chemical steps:
a decarboxylation, an oxidation, and the transfer to CoA.
Lipoamide, a coenzyme, is formed by the attachment of
the _______ to a ______ residue in another
enzyme in the complex, dihydrolipoyl transacetylase
(E2).
* The _____ linkages allow lipoamide to move between
different sites.
* The three enzymes of the pyruvate dehydrogenase
complex are structurally integrated, and the lipoamide
arm allows rapid movement of ________
from one active site of the complex to another.
vitamin lipoic acid, lysine
flexible
substrates and products
