Biochemistry Lecture Notes 20–30: TCA Cycle, ETC, PPP, Gluconeogenesis, Ethanol Metabolism, Lipids, Cholesterol, and Lipoproteins

A comprehensive set of question-and-answer flashcards covering TCA, ETC, gluconeogenesis, PPP, ethanol metabolism, lipid metabolism, and cholesterol/lipoprotein biology based on the provided lecture notes.

What is the role of the TCA Cycle?

The hub of biochemical metabolism in the cell by catalyzing the oxidation of Acetyl CoA to CO2 and H2O.

What does TCA do to glucose?

Completely oxidizes glucose to CO2.

What is the ATP yield per NADH in oxidative phosphorylation?

2.5 ATP.

What is the ATP yield per FADH2 in oxidative phosphorylation?

1.5 ATP.

What is the role of NADH and FADH2 in metabolism?

They carry electrons to the electron transport chain, leading to ATP production by oxidative phosphorylation.

What electron carriers are produced by the TCA cycle and where do they go?

NADH and FADH2 carry electrons to the ETC.

What is the net energy yield per TCA cycle in terms of high-energy carriers?

3 NADH, 1 FADH2, and 1 GTP.

What is the total ATP output from one turn of the TCA cycle?

9 ATP (7.5 from NADH, 1.5 from FADH2) plus 1 GTP.

What are the three stages of respiration?

Generate Acetyl-CoA, Oxidize Acetyl-CoA, and Reduce Electron Carriers.

Which vitamins participate in the pyruvate dehydrogenase reaction (pyruvate to acetyl CoA)?

Thiamine (B1, as TTP), Riboflavin (B2, as FAD), Pantothenic acid (as CoASH), and Niacin (as NAD+).

What is the function of E1 in PDH complex?

Pyruvate interacts with the TTP cofactor (thiamine) to aid decarboxylation and stabilization. (PDH E1)

What is the first step of converting pyruvate to acetyl CoA?

Loss of carbon dioxide from pyruvate (decarboxylation).

What is the second step of converting pyruvate to acetyl CoA?

Transfer of the acetyl group onto the lipoamide swinging arm.

What is the third step of converting pyruvate to acetyl CoA?

The swinging arm transfers two carbons to CoA, delivering the acetyl group.

What is the fourth step of converting pyruvate to acetyl CoA?

The two-carbon acetyl group moves to the citric acid cycle via CoA.

What is the fifth step of converting pyruvate to acetyl CoA?

Reduced lipoamide arm is reoxidized by transferring electrons to FAD, forming FADH2.

What is CoASH (CoA-SH)?

Coenzyme A; carries acetyl groups via its thiol group.

What happens when arsenic is introduced into the body?

Irreversible toxin that forms covalent bonds with lipoamide, shutting down energy production.

What inhibits regulation of Pyruvate Dehydrogenase?

High energy status: ATP, NADH, and acetyl CoA.

What activates the regulation of Pyruvate Dehydrogenase?

Low energy status: ADP, NAD+, Pyruvate, CoA-SH, and Ca2+.

Is Acetyl CoA anabolic or catabolic?

It can serve as both anabolic or catabolic depending on the pathway.

What is the business end of the Coenzyme A molecule?

The thiol group, which forms a high-energy thioester bond with acetyl.

What is the first step of the TCA cycle?

Condensation of oxaloacetate (OAA, a 4-carbon dicarboxylic acid) with acetyl-CoA to form citrate via citrate synthase.

What is the second step of the TCA cycle?

Citrate is rearranged to isocitrate via aconitase.

What is the third step of the TCA cycle?

Isocitrate to alpha-ketoglutarate via isocitrate dehydrogenase (NADH production and decarboxylation).

What is the fourth step of the TCA cycle?

Alpha-ketoglutarate to succinyl-CoA via alpha-ketoglutarate dehydrogenase (NADH, decarboxylation, CoA transfer).

What is the fifth step of the TCA cycle?

Succinyl-CoA to succinate via succinyl-CoA synthetase, forming GTP (or ATP) via substrate-level phosphorylation.

What is the sixth step of the TCA cycle?

Succinate to fumarate via succinate dehydrogenase (FADH2 produced).

What is the seventh step of the TCA cycle?

Fumarate to malate via fumarase (hydration).

What is the eighth step of the TCA cycle?

Malate to oxaloacetate via malate dehydrogenase (NADH produced).

Is the TCA cycle favorable or unfavorable energetically?

Favorable; it has a negative delta G overall.

Where are the TCA cycle control points located?

Highly exergonic steps; regulators at key junctions (e.g., OAA↔citrate, isocitrate↔AKG, AKG↔Succinyl-CoA).

What inhibits PDH conversion of acetyl-CoA to citrate?

NADH and Succinyl-CoA.

What inhibits Isocitrate Dehydrogenase (Isocitrate to AKG)?

NADH and ATP.

What activates Isocitrate Dehydrogenase?

ADP and Ca2+.

What activates AKG to Succinyl-CoA?

Ca2+.

What inhibits AKG to Succinyl-CoA?

Succinyl-CoA and NADH.

What form does ADP stabilize Isocitrate Dehydrogenase in?

The R form (more active).

What form does NADH stabilize Isocitrate Dehydrogenase in?

The T form (slower).

How is the TCA cycle related to anaplerosis?

It replenishes cycle intermediates (anaplerotic reactions) that are depleted by other pathways.

What are key concepts for the TCA that students should know?

Rate-limiting steps, committed steps, irreversible reactions, substrate regulation, feedback inhibition, compartmentation, hormonal and tissue-dependent regulation.

What is the final electron transport chain acceptor?

Oxygen, forming water.

What is Complex I’s main function?

Oxidation of NADH and pumping of 4 protons; transfer of electrons to coenzyme Q.

What is the function of Coenzyme Q (ubiquinone) in the ETC?

Transfers electrons from Complex I to Complex III.

What is the function of Complex III?

Pumps 4 protons into the intermembrane space and transfers electrons from Q to cytochrome c.

What is the function of Complex IV?

Reduces O2 to water and pumps protons into the intermembrane space.

What is the purpose of building a proton gradient in mitochondria?

Protons flow back through ATP synthase to generate ATP.

How many protons are transported per NADH through the ETC?

10 protons.

How many protons are transported per FADH2?

6 protons.

How many protons are used to synthesize ATP and import inorganic phosphate?

3 protons for ATP synthesis and 1 proton for inorganic phosphate import.

Does Complex II pump protons across the membrane?

No.

How does electron affinity change along the ETC?

Electrons are passed to carriers with progressively higher affinity for electrons.

What is Complex I’s alternative name?

NADH-Coenzyme Q Reductase.

What is oxidized and reduced in Complex I?

NADH is oxidized; Coenzyme Q is reduced.

What is Complex II’s function?

Oxidation of FADH2 to reduce CoQ (succinate-CoQ reductase).

What happens when amino acids bind to Complex I?

Conformational changes release H+ into the intermembrane space.

What is Complex II called?

Succinate-Coenzyme Q Reductase.

What does Coenzyme Q do with its accepted electrons?

Transfers electrons to Complex III.

What problems arise from CoQ defects?

Formation of superoxide and membrane damage.

What is Complex III?:

Coenzyme Q:Cytochrome C Oxidoreductase.

What is oxidized and reduced in Complex III?

Cytochrome C is reduced; Coenzyme Q is oxidized.

What is Complex IV called?

Cytochrome C Oxidase.

What is oxidized and reduced in Complex IV?

Oxygen is reduced; Cytochrome C is oxidized.

What is Complex V?

ATP Synthase.

What is the function of ATP Synthase?

Use the proton gradient to synthesize ATP.

What is the function of F1 in ATP synthase?

Catalyzes ATP synthesis from ADP and Pi.

How does the proton gradient drive ATP synthesis?

Protons flow through the rotor of ATP synthase, driving rotation and ATP formation.

What do protons bind to in Complex V?

A negatively charged amino group (Aspartate or Glutamate) in the c-ring subunits.

How does pKa influence proton movement in the membrane?

Low pKa favors proton binding at the membrane interface; high pKa favors release.

What is the overall power of the electrochemical gradient for ATP production?

ADP is phosphorylated to ATP; proton motive force is essential and depends on NADH or FADH2 as electron sources.

What is the function of the ATP–ADP translocase?

Moves ATP out of the mitochondrion and brings ADP in across the inner membrane.

How is Complex IV regulated?

Activity is related to the substrate availability.

What is the function of Uncoupling Protein I in brown fat?

Allows protons to re-enter the matrix without making ATP, releasing heat for thermoregulation.

What happens when an uncoupler is activated or ATP synthesis is less efficient?

Decreases ATP production and increases fat oxidation to compensate (thermogenesis).

Name some uncouplers.

2,4-Dinitrophenol (DNP), Dicumarol, Salicylate, microbial toxins, and uncoupling proteins.

How does ETC dysfunction affect the TCA cycle?

Anaplerotic imbalance can raise precursor levels that feedback inhibit TCA; can decrease acetyl-CoA oxidation and shift metabolism to lactate and pyruvate accumulation.

How does ETC dysfunction affect glycolysis?

Inhibits acetyl-CoA oxidation, increasing pyruvate and lactate; glycolysis can be inhibited.

How does ETC dysfunction affect acid-base balance?

Increased lactate production leads to acidosis (lactic acidosis).

How does ETC dysfunction affect ATP production?

Decreased ATP production.

What is an inhibitor of Complex I?

Rotenone.

What is an inhibitor of Complex II?

Malonate.

What is an inhibitor of Complex III?

Antimycin A.

What is an inhibitor of Complex IV?

CO and CN- (cyanide or carbon monoxide) inhibit complex IV.

What is an inhibitor of Complex V?

Oligomycin.

What are common symptoms of mitochondrial ETC deficiencies?

Weakness, cramping, severe fatigue.

How does cyanide poisoning affect the ETC?

Inhibits electron transport at cytochrome oxidase (Complex IV) by binding Fe3+. One of the most dangerous blockers.

How does anemia affect the ETC?

Low iron reduces Fe-S centers and cytochromes, impairing electron transport.

What is the effect of hypoxic injury on the ETC?

No oxygen means no final electron acceptor, ATP is depleted and muscle function is compromised.

What is the effect of malignant hyperthermia on the ETC?

Uncoupling of oxidative phosphorylation; ATP falls, TCA stimulated, CO2 production increases, causing respiratory acidosis.

What hormone drives the starved state?

Glucagon.

What determines how long we can fast?

Amount of adipose tissue available.

What drives ketone body production?

Fatty acid oxidation.

What does the brain use in the starving state?

Ketone bodies converted to acetyl-CoA for energy.

How do muscles respond in fasting/starved states?

Conserve protein; rely more on fatty acids for energy.

What is glycerol’s fate during fasting?

Glycerol enters liver for gluconeogenesis via DHAP and glyceraldehyde-3-phosphate.

What happens to glycogenolysis during fasting?

Rapid decrease and depletion within about 24 hours.

How do lipolysis and ketogenesis change during fasting?

Lipolysis and ketogenesis rapidly increase within hours, then slowly continue.

What happens to gluconeogenesis during fasting?

Rapid increase in activity during first day to days, then levels off.

What is gluconeogenesis?

Synthesis of glucose from non-carbohydrate precursors in the liver.

Why are the three irreversible steps of glycolysis tightly regulated?

To ensure glycolysis or gluconeogenesis predominates depending on cellular conditions.