CM13 - Energy Metabolism

Biomedical Sciences I

What is energy metabolism?

Complex biochemical processes that involve the conversion of nutrients into energy.

What are key metabolic pathways?

Intricate networks of biochemical reactions that interconvert various molecules to generate energy, synthesize biomolecules, and maintain cellular homeostasis.

What does a negative free energy (-ΔG) indicate?

A tendency for a reaction to proceed.

Reaction releases energy (exergonic).

What does +ΔG mean?

Reaction gains energy (endergonic).

How do reactions that require free energy input proceed?

They must be coupled to another reaction that releases at least that much energy.

What are metabolic pathways in terms of reactions?

Series of coupled reactions sharing intermediates.

How many high-energy phosphate bonds does ATP have?

2.

What is the hydrolysis reaction of ATP?

ATP → ADP + Pi (ΔG = –7.3 kcal).

Is ATP constantly consumed and regenerated?

Yes

What processes consume ATP?

Muscular contraction, active transport, and biosynthetic reactions.

How is ATP regenerated?

By the oxidation of food.

What is the energy potential of ATP compared to other nucleoside triphosphates?

They are equal:

ATP = CTP = GTP = UTP.

What are the major electron acceptors in catabolism?

NAD+ and FAD.

What do their reduced forms (NADH and FADH2) do?

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

What is the role of NADPH?

It is the primary electron donor in anabolism.

What are the steps in generating ATP from foods?

• Digestion (breakdown of carbohydrates, fats, proteins to small building blocks)

• Formation of acetyl-CoA by degradation of digestion products (glucose, fatty acids, glycerol, amino acids)

• Oxidation of acetyl-CoA in the TCA cycle, followed by electron transfer to the ETC, coupled with ATP formation

How is energy metabolism regulated?

• 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 are the other names for the TCA cycle?

Citric acid cycle and Krebs cycle.

What is the role of the TCA cycle?

Common pathway in fuel metabolism before conversion to CO2 + H2O + energy.

Where does most energy come from?

From the TCA cycle combined with the ETC.

How do most molecules enter the cycle?

As acetyl-CoA.

Where does the TCA cycle occur?

In the mitochondrial matrix.

What is the mitochondrion the site of?

Fuel oxidation and ATP synthesis.

Describe the mitochondrial dual-membrane system.

• Outer membrane (OMM): permeable to most small ions and molecules due to porin

• Inner membrane (IMM): folded into cristae, impermeable to most molecules, requires carriers for transport

• Intermembrane space (IMS): higher proton concentration

• Matrix (M): lower proton concentration; contains mtDNA/RNA and proteins for the TCA cycle and fatty acid oxidation

Is the TCA cycle an open or closed system?

Open system (compounds constantly entering and leaving).

What processes are linked to intermediates of the TCA cycle?

Amino acid synthesis, fatty acid synthesis, and gluconeogenesis.

Step 1: What is citrate synthesis?

Irreversible condensation of acetyl-CoA (2C) and oxaloacetate (4C) → citrate (6C), catalyzed by citrate synthase; activity depends on [oxaloacetate].

Step 2: What is citrate isomerization?

Reversible isomerization of citrate to isocitrate.

Step 3: What happens in oxidative decarboxylation of isocitrate?

Irreversible conversion of isocitrate to α-ketoglutarate by isocitrate dehydrogenase (IDH). This is the RATE-LIMITING STEP. Produces NADH and CO2.

How is isocitrate dehydrogenase regulated?

• Activators: ADP, Ca2+

• Inhibitors: ATP, NADH

Step 4: What happens in oxidative decarboxylation of α-ketoglutarate?

Irreversible conversion of α-ketoglutarate to succinyl-CoA; produces NADH and CO2; catalyzed by the α-ketoglutarate dehydrogenase complex.

Step 5: What happens in succinyl-CoA cleavage?

Reversible cleavage to succinate and CoA; coupled with phosphorylation of GDP → GTP.

Step 6: What happens in succinate oxidation?

Succinate → fumarate, with reduction of FAD → FADH2; reversible; catalyzed by succinate dehydrogenase (IMM enzyme).

Step 7: What happens in fumarate hydration?

Reversible hydration of fumarate → malate.

Step 8: What happens in malate oxidation?

Reversible oxidation of malate → oxaloacetate by mitochondrial malate dehydrogenase; produces NADH.

How is energy captured in the TCA cycle?

By electron transfer to NADH and FADH2, released in the ETC.

What direct high-energy molecule does the TCA cycle generate?

1 GTP (convertible to ATP).

What happens to the carbons of acetyl-CoA?

2 carbons enter as acetyl-CoA and exit as CO2.

What is the net reaction of the TCA cycle?

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

What are the regulated enzymes of the TCA cycle?

• Citrate synthase (inhibited by citrate)

• Isocitrate dehydrogenase (RATE-LIMITING, inhibited by NADH and ATP, activated by ADP and Ca2+)