Under _____ conditions, pyruvate enters the mitochondria and is converted to ________.
Acetyl CoA is the fuel for the...
Citric acid cycle
Oxidative decarboxylation of pyruvate and the reactions of the citric acid cycle occur within...
The mitochondrial matrix
Pyruvate translocase transports the pyruvate produced during glycolysis in the _______ into __________ in ____________.
Cytoplasm to mitochondria
In symport with H+
Pyruvate dehydrogenase complex catalyzes the oxidative phosphorylation of _______ to _______.
Pyruvate to acetyl CoA
Pyruvate dehydrogenase complex is ________ and a link between...
Link between glycolysis and the citric acid cycle
PDH requires 3 enzymes to synthesize acetyl CoA. What are they?
Pyruvate dehydrogenase component (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (E3)
The prosthetic group for E1 is...
The prosthetic group for E2 is...
The prosthetic group for E3 is...
3 steps of PDH are...
Transfer to CoA
What is the catalyst for the decarboxylation reaction?
E1 or pyruvate dehydrogenase component
*Combines with TPP
Step 2 of PDH:
Oxidation of TPP by E1
Step 3 of PDH:
Formation of acetyl CoA (E2) + dihydrolipoamide (reduced form)
Step 4 of PDH:
Dihydrolipoamide is oxidized back to lipoamide (E3)
What two conditions must be present for the coordinated catalysis of this reaction?
Flexible lipoamide arm
Structural integration of the 3 enzymes (must be tightly associated)
What happens if lipoamide or TPP are not present?
Pyruvate will not convert to Acetyl CoA
Acetyl CoA has two key principle fates:
Metabolism by the citric acid cycle
Incorporation into fatty acids
Because it is an irreversible reaction, acetyl CoA cannot convert back to ______ and therefore _____ cannot be used to make _____.
Lipids cannot form glucose from acetyl CoA
PDH is regulated by _________ and _________.
Covalent modification and allosteric interactions
A kinase associated with the complex __________ and __________ E1 subunit of PDH.
Phosphorylates and inactivates E1
A phosphatase associated with the complex removes the _______ and thereby _______ the enzyme.
Activates the enzyme
PDH also regulated by allosteric reactions, specifically...
PDH is inhibited by...
PDH activated by...
If there is a phosphotase deficiency, PDH is always ________ and therefore ______.
When inactive, PDH is converted to ______ leading to __________ and malfunctioning the ____________.
Converted to lactate
Leading to lactic acidosis
Beriberi: A neurological and cardiovascular disorder caused by dietary deficiency of _______ or ______.
Thiamine or vitamin B1
With Beriberi, PDH activity is _____ and results in...
Activity is low
Results in pyruvate accumulation.
No conversion to acetyl CoA? This limits ATP production!
What causes similar symptoms to those in Beriberi?
Exposure to mercury or arsenite
Arsenite and mercury bind to _________ and ______ PDH complex.
Bind to dihydrolipoamide
What relieves the inhibition of PDH by forming a complex with arsenite?
What is the arsenic-based chemical weapon used in WWI?
The prosthetic group _____________ is required for the transfer of the acetyl group to coenzyme A.
The Pyruvate Dehydrogenase (PDH) Complex is allosterically activated by high levels of:
The E2 enzyme (dihydrolipolyl transacetylase) of the pyruvate dehydrogenase complex contains _______________ as prosthetic group and catalyzes the___________________.
Lipoamide; transfer of the acetyl group to CoA.
How does the antidote for lewisite work?
BAL: Sulfhydryl reagent 2,3-dimercaptopropanol reacts arsenite and is then excreted