BIOCHEM CH.16 TCA CYCLE

Multistep reactions proceed in the Krebs Cycle for the oxidative decarboxylation of a-ketoglutarate, which requires all of the following except for

NAD+

Lipoic Acid

Thiamine Pyrophosphate

Coenzyme A

ATP

a-ketoglutarate dehydrogenase complex similar to the pyruvate dehydrogenase complex and requires the 5 cofactors

TPP, Lipoic Acid, Coenzyme A (CoA-SH)

FAD, NAD+ (Final Carrier)

How many NADH molecules are generated from the complete oxidation of one Glucose?

10 NADH Molecules

Glycolysis- 2 NADH & 2 Pyruvate

2 Pyruvate—> 2 Acetyl-CoA (PDH)

1 NADH per Pyruvate (2 Total)

1 TCA Turn (3 NADH)

2 Turns for 2 Acetyl-CoA (6 NADH)

10 Total

How many reducing equivalents (equal to electrons) are trasnferred to electron carriers after 1 turn of the TCA Cycle?

3 NADH & 1 FADH2 per turn

4 Reducing Equivalents

8 per glucose molecule

In mammals, which of the following does not occur during the citric acid cycle?

net synthesis of Oxaloacetate from Acetyl-CoA

Oxaloacetate is regenerated later from Malate via Malate Dehydrogenase

Malonate is a competitive inhibitor of succinate dehydrogenase. If malonate was added to a mitochondrial preparation that is oxidizing pyruvate as a substrate, which of the following compounds would you expect to decrease?

Fumarate

Succinate—>Fumarate via Succinate Dehydrogenase

The Citric Acid Cycle is regulated in a manner similar to Glycolysis. Which molecule is an allosteric activator of both of these pathways?

ADP

ADP activates isocitrate dehydrogenase (IDH) and α-ketoglutarate dehydrogenase.

That increases the rate of NADH and FADH₂ production → more electron carriers for the electron transport chain, which in turn generates ATP.

The Glyoxylate Cycle is similar to the Kreb’s Cycle, but differs in several important ways. What important molecule is conserved by the Glyoxylate but not Kreb’s?

CO2

The glyoxylate cycle conserves CO₂ because it bypasses the two decarboxylation steps of the TCA cycle, preventing carbon loss and allowing acetyl-CoA carbons to be used for making glucose instead of being released as CO₂.

The release of carbon dioxide from the complete oxidation of pyruvate can pose problems for cells. What molecule can easily be formed from carbon dioxide that can serve as a one carbon donor and double as a biological buffer?

Bicarbonate

The 2-Step reactions in the Citric Acid Cycle, in which the reactants lose CO2 are?

a-Ketoglutarate—> Succinyl-CoA

Isocitrate—> a-Ketoglutarate

Decarboxylatoin Reaction via Dehydrogenases 

Using currently accepted P/O ratios (1 NADH, 2.5 ATP, 1 FADH2, 1.5 ATP), what is the total ATP potential yield from 1 Acetyl-CoA in the Citric Acid Cycle?

10 ATP

Breakdown per 1 acetyl-CoA in TCA:

3 NADH × 2.5 = 7.5 ATP

1 FADH₂ × 1.5 = 1.5 ATP

1 GTP ≈ 1 ATP

= 7.5 + 1.5 + 1 = 10 ATP

What 2 chemical mechanisms change pyruvate to acetyl-CoA in the pyruvate dehydrogenase complex?

Dehydrogenation (Oxidation) electrons removed to reduce NAD+ and Decarboxylation removal of CO2 from Pyruvate

Oxidative Decarboxylation

Which combination of cofactors is involved in the conversion of pyruvate to acetyl-CoA?

TPP, Lipoic Acid, NAD+

Which of the following Kreb’s Cycle reactions is often followed rapidly by transphosphorylation?

Succinyl-CoA-Synthease

releases GTP or (ATP)

Which of the following cofactors is required for the conversion of succinate to fumarate in the Citric Acid Cycle?

FAD

Which of the following are not involved in the Kreb’s Cycle?

3-phosphoglycerate

A eukaryotic cell can use glucose (C6H12O6) and hexanoic acid (C6H12O2) as fuels for cellular respiration. On the basis of their structural formulas, which substance releases more energy per gram on complete combution to CO2 and H2O?

Hexanoic Acid releases more energy per gram since it has fewer oxygen atoms and is more reduced than glucose, so it yields more energy per gram.

After being oxidized by metabolic pathways from glycolysis to the Citric Acid Cycle, one Glucose can produce?

2 (ATP) Glycolysis 2 (GTP) TCA

10 NADH 2 Glycolysis 2 PDH 6 TCA

2 FADH2 (1 per turn) 2 Turns

6 CO2 2 PDH (4 TCA)

Citric Acid Metabolites in Order

1.) Acetyl-CoA

2.) Citrate

3.) Isocitrate

4.) a-Ketoglutarate

5.) Succinyl-CoA

6.) GTP (ATP)

7.) Succinate

8.) Fumarate

9.) Malate

10.) Oxaloacetate

Citric Acid Enzymes in Order

Acetyl-CoA→ Citrate

(Citrate Synthase)

Citrate→ Isocitrate

(aconitase)

Isocitrate→ a-Ketoglutarate

(isocitrate dehydrogenase) (NADH + CO2)

a-Ketoglutarate→ Succinyl-CoA

(a-ketoglutarate dehydrogenase complex)

(NADH + CO2)

Succinyl-CoA→Succinate

(Succinyl-CoA synthease) (GTP)

Succinate→ Fumarate

(succinate dehydrogenase) (FADH2)

Fumarate→ Malate

(Fumarase)

Malate→ Oxaloacetate

(Malate Dehydrogenase) (NADH)

(3 NADH per turn 2 CO2 1 GTP)

Pyruvate is produced in glycolysis and used by the Kreb’s Cycle in the mitochondrial matrix. How does pyruvate get into the matrix?

Facilitated Diffusion through a specific uniport.

The conversion of 1 mol of Pyruvate to 3 mol CO2 via Pyruvate Dehydrogenase and the Citric Acid Cycle also yields ? mol NADH, ? mol FADH2, and ? mol of ATP (GTP)?

3 mol NADH, 1 mol FADH2, 1 mol ATP (GTP)

1 Glucose is 6 NADH, 2 FADH2, 2 ATP

The power of the Kreb’s Cycle is partly in the ability to shuttle intermediates out for synthesis of important groups of molecules? What group of molecules are produced from Citrate?

Lipids an Sterols

Citrate can leave the mitochondria and be converted to acetyl-CoA in the cytosol, which is then used for fatty acid and cholesterol (sterol) synthesis.

Which of the following reaction generates GTP(ATP) in the Citric Acid Cycle?

Succinyl-CoA→ Succinate

What is the main purpose of the Citric Acid Cycle?

To oxidize acetyl-CoA into CO₂ while producing NADH, FADH₂, and GTP for ATP generation.

Where in the cell does the Citric Acid Cycle occur?

In the mitochondrial matrix

What is the overall net reaction for one turn of the TCA Cycle?

Acetyl-CoA + 3 NAD⁺ + FAD + GDP + Pi + 2 H₂O → 2 CO₂ + 3 NADH + FADH₂ + GTP + CoA + 3 H⁺.

How many NADH, FADH₂, and GTP are produced per acetyl-CoA?

3 NADH, 1 FADH₂, and 1 GTP.

How many ATP equivalents are produced per acetyl-CoA?

About 10 ATP (7.5 from NADH + 1.5 from FADH₂ + 1 from GTP).

How many ATP equivalents per glucose are produced from the TCA Cycle?

~20 ATP (2 acetyl-CoA × 10 ATP each).

Total ATP yield from full oxidation of one glucose molecule?

About 32 ATP (7 from glycolysis + 5 from PDH + 20 from TCA).

Which enzymes regulate the TCA Cycle?

Citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.

What inhibits the TCA Cycle?

High ATP, NADH, and succinyl-CoA (citrate also inhibits citrate synthase).

What activates the TCA Cycle?

ADP/AMP, NAD⁺, and Ca²⁺ (in muscle).

How is the Pyruvate Dehydrogenase Complex regulated?

PDH kinase (phosphorylates = inactive) and PDH phosphatase (dephosphorylates = active).

What activates PDH phosphatase?

Ca²⁺ and ADP → increase acetyl-CoA production for energy demand.

What are anaplerotic reactions?

Reactions that replenish TCA intermediates, like pyruvate → oxaloacetate via pyruvate carboxylase.

What are cataplerotic reactions?

Reactions that remove TCA intermediates for biosynthesis (e.g., amino acids, gluconeogenesis).

What is the glyoxylate cycle?

A modified TCA in plants/bacteria that bypasses CO₂ loss and conserves carbon for glucose synthesis.

Key enzymes unique to the glyoxylate cycle?

Isocitrate lyase and malate synthase.

Why can’t humans perform the glyoxylate cycle?

We lack isocitrate lyase and malate synthase, so we can’t convert fat to glucose directly.

What does “glyoxylate conserves CO₂” mean?

It skips decarboxylation steps so carbon is retained for biosynthesis instead of released as CO₂.

Which metabolites link the TCA Cycle to other pathways?

Citrate, α-ketoglutarate, succinyl-CoA, malate, and oxaloacetate.

What can citrate be used to synthesize?

Fatty acids and sterols (cholesterol).

What can α-ketoglutarate form?

Glutamate and other amino acids.

What can succinyl-CoA be used for?

Heme synthesis.

What can malate and oxaloacetate form?

Malate → glucose (via gluconeogenesis); oxaloacetate → aspartate and pyrimidines

How many reducing equivalents are generated per TCA turn?

3 NADH + 1 FADH₂ = 4 reducing equivalents (8 electrons).