TCA Cycle Energetics, Enzyme Inhibition and DNA Replication

The Tricarboxylic Acid (TCA) cycle, also called the Krebs cycle or citric acid cycle, is a cyclic series of reactions in which acetyl-CoA is oxidized to CO₂, producing reduced coenzymes NADH and FADH₂ and generating energy.

Energetics

For one acetyl-CoA:

• 3 NADH = 3 × 2.5 = 7.5 ATP
• 1 FADH₂ = 1 × 1.5 = 1.5 ATP
• 1 GTP = 1 ATP
• Total = 10 ATP per acetyl-CoA

Since one glucose produces 2 acetyl-CoA:

TCA yield = 20 ATP per glucose

Importance of the TCA Cycle

• Major pathway for the oxidation of acetyl-CoA.
• Produces ATP and GTP.
• Produces NADH and FADH₂ for the electron transport chain (ETC).
• Provides intermediates for amino acid synthesis.

Enzyme Inhibition

Definition

Enzyme inhibition is the reduction in enzyme activity due to the binding of an inhibitor to the enzyme.

A. Competitive Inhibition

The inhibitor competes with the substrate for the active site.

Effect:

• K_m increases
• V_max unchanged

Example: Malonate inhibits succinate dehydrogenase.

B. Non-Competitive Inhibition

The inhibitor binds at a site other than the active site.

Effect:

• V_max decreases
• K_m remains unchanged in the ideal pure non-competitive case.

C. Uncompetitive Inhibition

The inhibitor binds only to the enzyme-substrate complex.

Effect:

• K_m decreases
• V_max decreases

D. Irreversible Inhibition

The inhibitor permanently inactivates the enzyme, often by covalent modification.

Example: Organophosphorus compounds inhibit acetylcholinesterase.

DNA Replication

DNA replication is the process by which DNA produces an identical copy of itself.

Site: Nucleus in eukaryotic cells.

Steps of DNA Replication

1. DNA double helix unwinds.
2. Hydrogen bonds are broken.
3. Helicase unwinds DNA.
4. Primase forms RNA primer.
5. DNA polymerase adds nucleotides.
6. Leading strand is synthesized continuously.
7. Lagging strand is synthesized discontinuously.
8. Short fragments called Okazaki fragments are formed.
9. DNA ligase joins Okazaki fragments.

Replication is semiconservative, meaning each daughter DNA molecule contains one old strand and one newly synthesized strand.

RNA Transcription

Transcription is the synthesis of RNA from a DNA template.

Steps

• Initiation – RNA polymerase binds to the promoter.
• Elongation – RNA chain is synthesized.
• Termination – RNA synthesis stops.

Main types of RNA:

• mRNA – carries genetic information.
• tRNA – carries amino acids.
• rRNA – forms part of ribosomes.

Comparison Between DNA and RNA