Citric Acid Cycle Flashcards
What stage of cellular respiration is the citric acid cycle
Stage 2
Where does CAC take place
In the mitochondria
What is the word description of the Tricarboxcylic acid cycle?
acetyl groups enter the citric acid cycle, which enzymatically oxidizes them to CO2.
The energy released by oxidation is conserved in the reduced electron carriers NADH and FADH2.
Why is CAC known as the final common pathway for the aerobic respiration of macronutrients?
carbohydrate, lipid, and protein which are broken down into glucose, fatty acids, and most amino acids are metabolized to acetyl- CoA or intermediates of the cycle.
Why is the citric acid cycle important?
produces important precurors that form building blocks of many other molecules.
What molecules can be converted into Acetyl CoA?
Ketogenic AA
Ketone bodies
Pyruvate
FA
How is pyruvate from glycolysis transported to the CAC?
pyruvate/H+ symport in the inner mitochondrial membrane
Does pyruvate/H+ symport require energy to function?
Yes, stored energy is coming from IMM where there is an electrical potential gradiet
Where does the first reaction take place
In the mito of eukaryotes and the cystosol of prokaryotes
What enzyme catalysed the conversion of pyruvate to Acetyl CoA?
pyruvate dehydrogenase (PDH) complex,
What 3 distinct enzymes make up PDH complex
pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3).
Which 5 coenzymes are required for PDH complex to function?
thiamine pyrophosphate (TPP)
Flavin adenine dinucleotide (FAD)
CoA
nicotinamide adenine dinucleotide (NAD) lipoate
Which enzyme does TPP bind to?
active site of E1 pyruvate dehydrogenase
Which coenzyme bind to of E2?
dihydrolipoamide acetyltransferase (E2) binds to lipoate
Which Enzyme does FAD bind to?
flavin adenine dinucleotide binds to E3
What happens in E1
In the first step, E1 (pyruvate dehydrogenase) catalyzes oxidative decarboxylation of pyruvate. One carbon atom is removed from pyruvate as CO2.
The resulting 2-carbon molecule, hydroethyl is bound to TPP.
What happens in E2?
E2 (dihydrolipoamide acetyltransferase), which transfers the hydroethyl group from TPP to the oxidized form of lipoamide.
The acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced lipoamide.
What happens in E3
FAD-dependent E3 (dihydrolipoamide dehydrogenase) reoxidizes the lipoyl group E2. The electrons are accepted by FAD to form FADH2,
which is then donated to NAD+ to form NADH
Which Enzymes complexes are needed to form Acetyl CoA?
E1 – Pyruvate dehydrogenase
E2 – Dihydrolipoamide acetyltransferase
E3 – Dihydrolipoamide dehydrogenase
Which enzyme catalyses the overall reaction of the formation of Acetyl CoA?
Pyruvate dehydrogenase
Is the formation of acetyl CoA reversible?
No it is irreversible
What kind of reaction is the formation acetyl CoA?
Oxidative decarboxylation in which the carboxyl group is removed from pyruvate as a molecule of CO2 and the two remaining carbons become the acetyl group of acetyl-CoA.
What does thiamine deficiency cause?
CNS problems is because brain cells are unable to produce sufficient ATP (via the TCA cycle) if the PDH complex is inactive.
Beriberi, characterized by loss of neural function.
Wernicke-Korsakoff, an encephalopathy-psychosis syndrome due to thiamine deficiency, may be seen with alcohol abuse.
Which B vitamin is thiamine?
B1
What serves as an indicator for defects in pyruvate oxidation?
elevated level of pyruvate in the blood
What causes the activation of PDH complex
The accumulation of AMP, CoA, and NAD+ causes activation allosterically
Which protein phosphorylates and inhibits PDH Complex?
PDH kinase
What activates PDH Kinase
ATP, acetyl-CoA and NADH.
What inhibits PDH complex?
pyruvate
Which enzyme activates E1 by removing the phosphorylation group by hydrolysis?
PDH phosphatase
Which mineral strongly activates PDH phosphatase?
Calcium
What is the most common cause of congenital lactic acidosis.
deficiency in the E1 component of the PDH complex
What is the significance of Pyruvate dehydrogenase deficiency?
causes problems for the brain, which relies on the TCA cycle for most of its energy and is particularly sensitive to acidosis.
What are the symptoms of Pyruvate dehydrogenase deficiency?
neurodegeneration, muscle spasticity and, in the neonatal onset form, early death.
Which enzyme complex defect affects both males and females and is classified as X- linked dominant?
E1: pyruvate dehydrogenase
What treatment can be done for PDH deficiency
dietary restriction of carbohydrate and supplementation with TPP may
What is the first reaction of CAC
What is the first reaction of CAC
- the condensation of acetyl-CoA with oxaloacetate to form citrate, catalyzed by citrate synthase
What is the second reaction of CAC
2.
Formation of Isocitrate via cis-Aconitate: Citrate is isomerized to isocitrate by the enzyme aconitase.
What inhibits the TCA cycle? How?
Fluoroacetate
first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.
What inhibits TCA cycle?
Fluoroacetate
first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.
What inhibits the TCA cycle?
Fluoroacetate
• Fluoroacetate is first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.
Source of Fluoroacetate?
A range of plant species
Some flourinated compounds such as in anticancer agents, pesticides, and industrial chemicals can
be metabolized to fluoroacetate.
What is the 3rd reaction of TCA Cycle?
- Oxidation of Isocitrate to α-Ketoglutarate and CO2:
isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form α-ketoglutarate and CO2
Which is the first rate limiting step
Reaction 3
What and how is Isocitrate dehydrogenase activated?
Isocitrate dehydrogenase is allosterically activated by ADP and Ca2+
What inhibits isocitrate dehydrogenase?
ATP and NADH.
What is the 4th reaction in TCA
oxidative decarboxylation, in which α-ketoglutarate is converted to succinyl-CoA and CO2 by the action of the α-ketoglutarate dehydrogenase complex.
What cofactors/enzymes are needed for reaction 4 to take place?
TPP, lipoid acid, CoASH, FAD and NAD+
Why are those specific cofactors/enzymes needed for reaction 4 to take place?
•α-Ketoglutarate dehydrogenase is nearly identical to PDH in terms of reactions catalysed and its structural features
What inhibits α-Ketoglutarate dehydrogenase complex ?
its products, NADH and succinyl CoA,
What activates α-Ketoglutarate dehydrogenase complex?
Ca2+
What is the fifth reaction in TCA
Succinyl-CoA is cleaved by Succinyl-CoA synthetase to form Succinate and GTP
reaction is coupled to phosphorylation of guanosine diphosphate (GDP) to guanosine triphosphate (GTP
What is GTP used for?
mitochondrial synthesis of proteins, RNA and DNA.
What is the other fate of GPT?
GTP formed can donate its phosphoryl group to ADP to form ATP, in a reversible reaction catalyzed by nucleoside diphosphate kinase.
What is the 6th TCA cycle reaction?
Oxidation of Succinate to Fumarate: The succinate is oxidized to fumarate by the flavoprotein succinate dehydrogenase:
Which enzyme is the only one that is membrane bound in the TCA in eukaryotes
succinate dehydrogenase is tightly bound to the inner mitochondrial membrane
What activates Succinate dehydrogenase?
ATP and succinate
What inhibits Succinate dehydrogenase?
Malonate (analog of succinate)
oxaloacetate
What is the 7th reaction in the sequence?
The reversible hydration of fumarate to L-malate is catalyzed by fumarase
OH and H are used together with the enzyme fumarase to form Malate
What is the 8th and final reaction of the TCA cycle?
NAD+-linked L-malate dehydrogenase catalyzes the oxidation of L- malate to oxaloacetate:
