***11. Energy Metabolism

What is energy metabolism?

Refers to the complex biochemical processes that involve the conversion of nutrients into energy.

What do key metabolic pathyways do?

Intricate networks of biochemical reactions that interconvert various molecules to:

• generate energy

• synthesize biomolecules

• maintain cellular homeostasis

Exergonic reaction:

• -ΔG

• Reaction releases energy

Endergonic reaction:

• +ΔG

• Reaction gains energy.

Free energy change

A reaction that requires free energy input must be coupled to another reaction that releases at least that much energy. (coupled reactions)

What are coupled reactions?

A pairing of two chemical processes where an energy-releasing (spontaneous) reaction drives an energy-requiring (non-spontaneous) reaction through a shared intermediate.

What are metabolic pathways?

A series of coupled reactions sharing intermediates.

T/F: ATP is constantly consumed and regenerated.

True.

What processes consume ATP?

• Muscular contraction

• Active Transport

• Biosynthetic reactions

How is ATP regenerated?

Regenerated by the oxidation of food.

ATP Hydrolysis:

ADP + Pi (ΔG = -7.3kcal)

How many phosphate bonds does ATP have?

2 high-energy phosphate bonds.

Energy Potential ATP:

ATP = CTP = GTP = UTP

How many major electron acceptors are in catabolism?

2.

What are the major electron acceptors in catabolism?

• Nicotinamide adenine dinucleotide (NAD+)

• Flavin adenine dinucleotide (FAD)

What is the primary electron donor in anabolism?

NADPH.

(phosphorylated derivative of NADH).

What do the reduced forms of NADH and FADH2 do?

Transfer electrons to the electron transport chain and eventually to O2 to generate ATP.

What is Catabolism?

The breakdown of complex molecules.

Does catabolism yield energy or require energy?

Yields energy.

Is catabolism oxidative or reductive?

Generally oxidative.

What is Anabolism?

Synthesis of complex molecules.

Is anabolism oxidative or reductive?

Generally reductive.

Does anabolism require energy or yield energy?

Requires energy.

Generation of ATP from foods:

• Digestion

  • Formation of acetyl CoA by degradation of digestion products.

  • Oxidation of acetyl CoA in the TCA → transfer of electrons to ETC → forms ATP.

What helps food break down to convert food to energy?

Acetyl-CoA.

Where does the Citric Acid Cycle (Krebs Cycle) take place?

Inside the mitochondria.

What is the regulation of energy metabolism?

Tight regulation to maintain the balance between energy production and utilization.

• Compartmentalization (cytosol vs mitochondria)

• Feedback regulation (high-energy vs low-energy states)

• Hormonal control (insulin vs glucagon)

• Signaling (gene expression regulation in response to external factors)

What is the TCA cycle also called?

Krebs Cycle or Citric Acid Cycle.

What is the most common pathway in fuel metabolism?

TCA.

Where does most energy come from?

Comes from TCA combined with ETC.

Many molecules enter the TCA as:

Acetyl-CoA.

Where does the TCA occur?***

Mitochondrial Matrix.

What is the mitochondria the site for?

• Fuel oxidation

• ATP synthesis

What is the site of fuel oxidation and ATP synthesis?

Mitochondria.

Mitochondria Structure:

• Outer Membrane (OMM)

• Inner Membrane (IMM)

• Intermembrane Space (IMS)

• Matrix (M)

What kind of membrane system does the mitochondria have?

Dual-membrane system.

Outer Membane: Mitochondria

Permeable to most small ions and molecules, due to the channel protein porin.

What kind of protein is porin?

Channel protein.

What do porins do?

Act as water-filled channels that allow passive diffusion of small, hydrophilic molecules across cellular membranes.

Inner Membrane: Mitochondria

Folded into ridges called cristae, is impermeable to most molecules; carriers are required for transport across this membrane.

What part of the mitochondria requires carriers to transport molecules?

Inner membrane.

Intermembrane Space: Mitochondria

Higher proton concentration.

Matrix: Mitochondira

Lower proton concentration; contains mtDNA / RNA and proteins involved in the TCA cycle and FA oxidation.

What part of the mitochondria has high proton concentration?

Intermembrane space.

What part of the mitochondria has low proton concentration?

Matrix.

What kind of system is the TCA considered and why?

Open-system because compounds are constantly coming and leaving to fulfill other cellular needs.

TCA integrates various fuel metabolisms such as:

• Carbs

• Amino Acids

• Folic Acids

TCA Reaction Sequence

1. Citrate Synthesis

2. Citrate Isomerization

3. Oxidative decarboxylation of Isocitrate

4. Oxidative decarboxylation of a-ketoglutarate

5. Succinyl CoA cleavage

6. Succinate Oxidation

7. Fumarate Hydration

8. Malate Oxidation

What is Citrate Synthesis?

The irreversible condensation between acetyl CoA (2C) and oxaloacetate (4C) → citrate (6C).

What is citrate synthesis catalyzed by?

Citrate Synthase.

What step is Citrate Synthesis?

Step 1.

Is Citrate Synthesis reversible or irreversible?

Irreversible.

What does citrate synthesis activity depend on?

Oxaloacetate.

What is Citrate Isomerization?

Isomerization to isocitrate.

Is citrate isomerization reversible or irreversible?

Reversible.

What step is Citrate Isomerization?

Step 2.

What is Oxidative decarboxylation of isocitrate?

Irreversible oxidative decarboxylation of isocitrate → a-ketoglutarate.

What does Oxidative decarboxylation of isocitrate produce?

• NADH

• CO2

What is the rate limiting-step of the TCA?

Step 3: Oxidative decarboxylation of isocitrate

What step is Oxidative decarboxylation of isocitrate?

Step 3.

Isocitrate dehydrogenase allosteric regulation: Activators

• ADP

• Ca²+

Isocitrate dehydrogenase allosteric regulation: Inhibitors

• ATP

• NADH

What is the rate-limiting enzyme in the TCA cycle?

Isocitrate dehydrogenase !!!!!

What is Oxidative decarboxylation of a-ketoglutarate?

Irreversible oxidative decarboxylation of a-ketoglutarate → succinyl CoA.

What does Oxidative decarboxylation of a-ketoglutarate produce?

• NADH

• CO2

Is Oxidative decarboxylation of a-ketoglutarate reversible or irreversible?

Irreversible.

What is Oxidative decarboxylation of a-ketoglutarate catalyzed by?

a-ketoglutarate dehydrogenase complex.

What step is Oxidative decarboxylation of a-ketoglutarate?

Step 4.

What is Succinyl-CoA cleavage?

Reversible cleavage of succinyl-CoA → succinate CoA.

What step is Succinyl CoA Clevage?

Step 5.

Is Succinyl CoA cleavage reversible or irreversible?

Reversible.

Succinyl CoA cleavage is simultaneously coupled with ___.

Phosphorylation of GDP to GTP.

What is Succinate Oxidation?

Succinate oxidated to fumarate, with reduction of FAD to FADH2.

Is succinate oxidation reversible or irriversible?

Reversible.

What catalyzes succinate oxidation?

Succinate dehydrogenase.

Where is succinate dehydrogenase found?

Embedded in the inner mitochondrial membrane.

What step is succinate oxidation?

Step 6.

What is Fumarate hydration?

Fumarate hydrated to malate.

Is Fumarate hydration reversible or irriversible?

Reversible.

What step is Fumarate oxidation?

Step 7.

What is Malate Oxidation?

Malate oxidized to oxaloacetate, which can reenter the cycle.

What does Malate oxidation produce?

NADH.

Is Malate oxidation reversible or irriversible?

Reversible.

What catalyzes malate oxidation?

Mitochondrial malate dehydrogenase.

What step is malate oxidation?

Step 8.

What is produced from the TCA? *****

• 3 NADH

• 1 FADH

• 1 GTP

How many ATP’s can be produced from a single molecule of acetyl-CoA? ***

Poetntially 12 ATP’s.

Regulated Enzymes in TCA:

• Citrate Synthase

• Isocitrate dehydrogenase

What is citrate synthase inhibited by?

Citrate.

What is isocitrate dehydrogenase inhibited by?

• NADH

• ATP

What is isocitrate dehydrogenase activated by?

• ADP

• Ca²+