MMT: TCA cycle Flashcards
Which TCA cycle intermediate(s) can be used for fatty acid synthesis?
citrate
Which TCA intermediate(s) can be used for amino acid synthesis
a-ketogluterate and oxaloacetate
Which TCA cycle intermediate(s) can be used in heme synthesis
Succinyl CoA
Which TCA cycle intermediate(s) can be used in gluconeogenesis?
malate and oxaloacetate
Can TCA cycle operate when there is no oxygen? Can glycolysis?
no; yes
where are the enzymes for the TCA cycle found?
the mitochondrial matrix
What do we do with pyruvate in anaerobic conditions?
Lactate fermentation; we convert pyruvate to lactate and 2 protons, generating NAD+ in the process
How does pyruvate enter the matrix?
It enters the intermembrane space through a VDAC pore, then enters the matrix via an MPC. The negative charge on pyruvate must be balanced, so a proton enters with the pyruvate.
list the intermediates in the TCA cycle
citrate, isocitrate, a-ketogluterate, succinyl CoA, succinate, fumrate, malae, oxaloacetate
list the enzymes in the TCA cycle
aconitase, isocitrate dehydrogenase, a-ketogluterate dehydrogenase, sunnincyl CoA synthase, succinate dehydrogenase, fumrase, malate dehydrogenase, citrate synthase
List the enzymes that yield CO2
Isocitrate dehydrogenase, a-ketoglutarate dehydrogenase
List the enzymes that yield NADH
Isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, malate dehydrogenase
List the enzymes that yield GTP
Succinyl CoA synthase
List the enzymes that yield FADH2
succinate dehydrogenase
What high energy bond is found in acetyl CoA
thioester bond
What is the rate-limiting reaction in the TCA cycle?
Isocitrate dehydrogenase
Note the biological roles of GTP.
Protein synthesis, signal transduction, or convert to ATP
- Calculate the yield of ATP from the oxidation of acetyl CoA.
10; 2.5 per NADH, 1.5 per FADH2, and 1 GTP
What is the role of the pyruvate dehydrogenase component of pyruvate dehydrogenase complex? What prosthetic group does it need?
Oxidative decarboxylation of pyruvate; TPP
What is the role of the dihidrolipoyl transacetylase in the pyruvate dehydrogenase complex? What prosthetic group does it require?
Transfers an acetyl group to CoA; lipoamide
What is the role of the dihidrolipoyl dehydrogenase in the pyruvate dehydrogenase complex? What prosthetic group does it require?
Regenerates the oxidized form of lipoamide; FAD
Lipoamide is connected to what amino acid? What is the important bond in the complex?
Lysine; a reactive disulfide bond
describe the the two general ways pyruvate dehydrogenase can be regulated?
energy charge: high ATP/NADH deactivates pyruvate dehydrogenase
phosphorylation: phosphorylating pyruvate dehydrogenase deactivates it
dephosphorylating pyruvate dehydrogenase is influenced by which two molecules?
calcium and insulin; both increase pyruvate dehydrogenase
leigh’s disease: what causes it, whata re the symptoms, and where are the mutations found
Direct mutation in pyruvate dehydrogenase. Impaired mitochondrial function, chronic lack of energy and CNS issues. We’ll convert pyruvate to lactate and develop metabolic acidosis. Mutation can be in E1 component or PDH phosphatase
how can leigh’s disease be treated
Can be treated with thiamine, taking in leucine and lysine, high fat and low carb diet, oral bicarb or citrate
Arsenic impacts what enzyme in the pyruvate dehydrogenase complex
E2 of the Pyruvate dehydrogenase complex; it binds to lipoic acid causing an accumulation of lactate that will impact the brain and lead to death
What conditions can be associated with altered PDH levels?
Alzheimer’s and Parkinson’s, leigh’s disease, type II diabetes
Low iron would impact which enzyme in the TCA cycle?
aconitase
Compare the reactions catalyzed by the α-ketoglutarate dehydrogenase complex to those catalyzed by the pyruvate dehydrogenase complex.
They require the same cofactors but have slightly different enzymes. They are both made of an E1, E2, and E3, with just minor changes.
Describe the role of anaplerotic reactions and specifically the function of pyruvate carboxylase to replenish oxaloacetate
Used to make more oxaloacetate so we can make more energy via gluconeogenesis or amino acid synthesis without stalling the TCA cycle
Oxaloacetate can be used to make ___
Glucose via gluconeogenesis