Ever feel like the citric acid cycle is a complex metabolic maze? Put your skills to the ultimate test with our citric acid cycle quiz, crafted to challenge your grasp of each step - from citrate formation to oxaloacetate regeneration. Along the way, you'll reinforce key concepts in the cellular respiration krebs cycle, sharpen your understanding of electron carriers, and predict ATP yield with confidence. Think of it as a TCA cycle quiz turned into an interactive citric acid cycle game. Ready to get started? Click here to launch the citric acid cycle quiz or explore our krebs cycle quiz and challenge yourself now!
What is the primary location of the citric acid cycle within eukaryotic cells?
Mitochondrial matrix
Cytosol
Intermembrane space
Inner mitochondrial membrane
The citric acid cycle occurs in the mitochondrial matrix where enzymes and substrates are concentrated. This compartmentalization allows for efficient oxidation of acetyl-CoA and production of electron carriers. The mitochondrial inner membrane houses the electron transport chain, but the cycle itself is in the matrix. More info.
Which molecule condenses with acetyl-CoA to begin the citric acid cycle?
Oxaloacetate
Succinyl-CoA
Citrate
?-Ketoglutarate
Oxaloacetate combines with acetyl-CoA via citrate synthase to form citrate, initiating the cycle. This condensation step is highly exergonic and essentially irreversible under physiological conditions. Oxaloacetate availability is a key control point for cycle flux. More info.
Which enzyme catalyzes the first committed step of the citric acid cycle?
Citrate synthase
Aconitase
Isocitrate dehydrogenase
?-Ketoglutarate dehydrogenase
Citrate synthase catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate, marking the first committed step. It is highly regulated and essentially irreversible in the cycle. Aconitase and dehydrogenases act later in the pathway. More info.
How many NADH molecules are produced per turn of the citric acid cycle?
Three
Two
Four
One
Three NADH molecules are generated by isocitrate dehydrogenase, ?-ketoglutarate dehydrogenase, and malate dehydrogenase. Each NADH can yield about 2.5 ATP when fed into the electron transport chain. This NADH production is central to the cycle’s energy payoff. More info.
Which intermediate is a six-carbon tricarboxylic acid formed in the first step of the cycle?
Citrate
Succinate
Fumarate
Malate
Citrate is the six-carbon tricarboxylic acid produced when acetyl-CoA and oxaloacetate condense. It is then isomerized into isocitrate via aconitase. Succinate, fumarate, and malate are four-carbon intermediates produced later in the cycle. More info.
How many carbon dioxide molecules are released per acetyl-CoA oxidized in the citric acid cycle?
Two
One
Three
None
Two CO? molecules are released per acetyl-CoA: one during isocitrate to ?-ketoglutarate and one during ?-ketoglutarate to succinyl-CoA. These decarboxylation steps are irreversible and essential for complete oxidation of the two-carbon acetyl group. More info.
Which step of the cycle generates a molecule of GTP (or ATP) via substrate-level phosphorylation?
Succinyl-CoA to succinate
Malate to oxaloacetate
?-Ketoglutarate to succinyl-CoA
Isocitrate to ?-ketoglutarate
Succinyl-CoA synthetase converts succinyl-CoA to succinate, producing GTP (or ATP in some tissues) by substrate-level phosphorylation. This is the only direct ATP/GTP generating step in the cycle. Other steps produce NADH or FADH? instead. More info.
Which enzyme is responsible for the isomerization of citrate to isocitrate?
Aconitase
Citrate synthase
Isocitrate dehydrogenase
Fumarase
Aconitase catalyzes the reversible conversion of citrate to isocitrate via the intermediate cis-aconitate. This step is necessary because citrate cannot be oxidized directly; its tertiary alcohol must be moved. Aconitase contains an iron–sulfur cluster that assists in the dehydration–rehydration mechanism. More info.
Which enzyme catalyzes the oxidative decarboxylation of isocitrate to ?-ketoglutarate?
Isocitrate dehydrogenase
Aconitase
?-Ketoglutarate dehydrogenase
Malate dehydrogenase
Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to ?-ketoglutarate and produces NADH and CO?. It is a key regulatory enzyme sensitive to ATP/ADP and NADH/NAD? ratios. There are both NAD?- and NADP?-dependent isoforms. More info.
Which coenzyme is required by ?-ketoglutarate dehydrogenase for catalysis?
Thiamine pyrophosphate (TPP)
Biotin
Pyridoxal phosphate (PLP)
Cobalamin
?-Ketoglutarate dehydrogenase requires thiamine pyrophosphate (TPP) as a coenzyme, similar to pyruvate dehydrogenase. TPP stabilizes the carbanion intermediate during decarboxylation. Vitamin B? deficiency disrupts this enzyme, impairing the cycle. More info.
Which step produces FADH? in the citric acid cycle?
Succinate to fumarate
Malate to oxaloacetate
Citrate to isocitrate
?-Ketoglutarate to succinyl-CoA
Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, reducing FAD to FADH?. This enzyme is embedded in the inner mitochondrial membrane as complex II of the electron transport chain. The FADH? produced transfers electrons directly to ubiquinone. More info.
Which product of the citric acid cycle can be directly used for gluconeogenesis via conversion to oxaloacetate?
Malate
Succinate
Fumarate
Citrate
Malate can be exported to the cytosol and converted to oxaloacetate by malate dehydrogenase in the gluconeogenic pathway. This shuttle helps transfer reducing equivalents and carbon skeletons. Succinate and fumarate are less directly linked. More info.
Which metabolite acts as a feedback inhibitor of citrate synthase?
ATP
NADH
ADP
AMP
ATP inhibits citrate synthase, signaling high energy status and reducing the flux through the cycle. Citrate itself also inhibits the enzyme allosterically. NADH inhibits multiple dehydrogenases but ATP is the primary feedback inhibitor of the first step. More info.
Which ion activates isocitrate dehydrogenase in the citric acid cycle?
Mg²?
Ca²?
Zn²?
Fe²?
Calcium ions activate isocitrate dehydrogenase in mitochondria, linking increased cytosolic Ca²? (e.g., during muscle contraction) to enhanced cycle flux. Magnesium is required as a general cofactor but Ca²? specifically modulates activity. More info.
Which shuttle transfers NADH from glycolysis into mitochondria for use in the citric acid cycle and oxidative phosphorylation?
Malate–aspartate shuttle
Glycerol-3-phosphate shuttle
Pentose phosphate shuttle
Citrate shuttle
The malate–aspartate shuttle transports reducing equivalents from cytosolic NADH into the mitochondrial matrix by converting oxaloacetate to malate. In the matrix, malate is reoxidized to oxaloacetate, regenerating NADH for the electron transport chain. The glycerol-3-phosphate shuttle also transfers reducing power but yields FADH?. More info.
Which regulatory enzyme in the citric acid cycle is allosterically activated by ADP?
Isocitrate dehydrogenase
Citrate synthase
Succinate dehydrogenase
Fumarase
Isocitrate dehydrogenase is allosterically activated by ADP (and inhibited by ATP), matching energy production to demand. ADP binding increases enzyme affinity for isocitrate. Citrate synthase is inhibited by ATP but less responsive to ADP. More info.
Which anaplerotic enzyme replenishes oxaloacetate for the citric acid cycle?
Pyruvate carboxylase
Citrate lyase
Malate synthase
Fumarase
Pyruvate carboxylase catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, replenishing cycle intermediates. It requires biotin as a cofactor and is activated by acetyl-CoA. This anaplerotic reaction maintains cycle flux when intermediates are withdrawn for biosynthesis. More info.
What is the net number of ATP equivalents produced per acetyl-CoA oxidized in the citric acid cycle (including oxidative phosphorylation)?
10
12
8
6
Each cycle yields 3 NADH (2.5 ATP each), 1 FADH? (1.5 ATP), and 1 GTP (1 ATP), totaling 10 ATP equivalents per acetyl-CoA. This calculation assumes standard P/O ratios. The exact yield can vary slightly with membrane leakiness and shuttle use. More info.
Which metabolite directly inhibits ?-ketoglutarate dehydrogenase through product feedback?
Succinyl-CoA
Citrate
Oxaloacetate
Succinate
Succinyl-CoA, the product of ?-ketoglutarate dehydrogenase, binds to the enzyme complex and inhibits its activity by feedback inhibition. This regulation prevents over-accumulation of cycle intermediates. It also resembles how pyruvate dehydrogenase is regulated by acetyl-CoA. More info.
Which citric acid cycle enzyme contains an iron–sulfur cluster essential for its activity?
Aconitase
Malate dehydrogenase
Fumarase
Succinate thiokinase
Aconitase contains a [4Fe-4S] iron–sulfur cluster that is critical for the dehydration–rehydration mechanism converting citrate to isocitrate. Loss of the cluster inactivates the enzyme and can be used as a sensor of oxidative stress. No other cycle enzyme uses this cofactor. More info.
Which metabolic condition leads to accumulation of citrate and inhibits glycolysis in the cytosol?
High ATP and citrate levels
High ADP and AMP levels
Low acetyl-CoA
High NAD?/NADH ratio
Elevated citrate spills into the cytosol and inhibits phosphofructokinase-1, slowing glycolysis when energy is ample. High ATP amplifies this effect by directly inhibiting PFK-1. This cross-talk ensures balance between carbohydrate breakdown and TCA cycle flux. More info.
Which enzyme defect would most directly cause lactic acidosis due to impaired entry of pyruvate into the citric acid cycle?
Pyruvate dehydrogenase
Citrate synthase
Aconitase
Malate dehydrogenase
A pyruvate dehydrogenase deficiency prevents pyruvate conversion to acetyl-CoA, forcing excess pyruvate into lactate production and causing lactic acidosis. Other cycle enzymes act downstream and would not directly divert pyruvate to lactate. More info.
Which step in the cycle is most thermodynamically favorable under standard conditions?
Citrate synthase reaction
Aconitase reaction
Malate dehydrogenase reaction
Succinate dehydrogenase reaction
The citrate synthase step has the largest negative ?G°?, making it highly exergonic and effectively irreversible in vivo. This drives the cycle forward and provides a control point. Other steps, such as aconitase, are near equilibrium. More info.
Which enzyme bypasses the two decarboxylation steps of the citric acid cycle in the glyoxylate shunt to allow net conversion of acetyl-CoA into four-carbon intermediates?
Isocitrate lyase
Malate synthase
Citrate lyase
Fumarate hydratase
Isocitrate lyase cleaves isocitrate into succinate and glyoxylate, bypassing the CO?-releasing steps and enabling net synthesis of C4 compounds from acetyl-CoA in the glyoxylate cycle. This adaptation is found in bacteria, plants, and fungi. Malate synthase then condenses glyoxylate with a second acetyl-CoA. More info.
Under standard conditions, which citric acid cycle reaction has the most negative ?G°? and thus contributes strongly to pathway directionality?
Oxaloacetate + acetyl-CoA ? citrate
Succinate ? fumarate
Malate ? oxaloacetate
Isocitrate ? ?-ketoglutarate
The citrate synthase reaction (oxaloacetate + acetyl-CoA ? citrate) has the largest negative standard free energy change (?G°? ? –31.4 kJ/mol), making it highly exergonic and essentially irreversible. This thermodynamic drive ensures cycle continuity. Other steps have smaller ?G°? values and can approach equilibrium in cells. More info.
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Study Outcomes
Recall Key Intermediates -
Identify and memorize the main substrates and products in each step of the citric acid cycle quiz to reinforce your metabolic pathway knowledge.
Explain Enzymatic Roles -
Describe the function of critical enzymes in the TCA cycle quiz and how they facilitate energy production during cellular respiration.
Analyze Regulatory Mechanisms -
Examine the control points within the Krebs cycle quiz to understand how flux is adjusted in response to cellular energy demands.
Apply Metabolic Integration -
Connect the citric acid cycle game to glycolysis and the electron transport chain to see how carbon flow affects overall ATP yield.
Predict Pathway Outcomes -
Use quiz scenarios to anticipate changes in metabolite levels under varying conditions, such as high NADH or low oxygen.
Evaluate Energy Yield -
Calculate the net production of NADH, FADHâ‚‚, and GTP per cycle turn to gauge the efficiency of cellular respiration.
Cheat Sheet
Entry of Acetyl-CoA and Citrate Formation -
Acetyl-CoA condenses with oxaloacetate via citrate synthase to form citrate in a highly exergonic reaction (Nelson & Cox, Lehninger Principles). This committed step drives the TCA cycle forward and is tightly regulated to match cellular energy demand.
Oxidative Decarboxylation Steps -
Isocitrate dehydrogenase converts isocitrate to α-ketoglutarate, releasing CO₂ and reducing NAD⺠to NADH, followed by α-ketoglutarate dehydrogenase generating succinyl-CoA, another CO₂, and NADH (Alberts et al., Molecular Biology of the Cell). These two key steps account for two of the cycle's three NADH-producing oxidations.
Substrate-Level Phosphorylation and GTP/ATP Generation -
Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate, coupled to GTP (or ATP) formation via nucleoside diphosphate kinase, representing the sole substrate-level phosphorylation in the TCA cycle (Voet & Voet, Biochemistry). This step provides direct energy currency before further oxidation.
Mnemonics for Cycle Intermediates -
Use "Citrate Is Krebs' Starting Substrate For Making Oxaloacetate" to recall the eight intermediates in order: citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaloacetate. This mnemonic is invaluable for quick recall during a citric acid cycle quiz or tca cycle quiz and boosts retention under pressure.
Regulation by Key Enzymes -
Citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase are the primary control points, responding to ATP/ADP ratios, NADH levels, and availability of substrates (FDA Handbook on Metabolic Regulation). Allosteric activators like ADP enhance flux, while NADH and ATP act as feedback inhibitors to balance energy production with demand.
