BIOC*2580 - 7

Coenzymes and Cofactors Discussion

Recap of Last Session

  • NAD and NADP discussed previously.

  • Examined redox chemistry of NAD and NADP, establishing similarities.

Structure of Russell Group (Last Slide)

  • Display of redox chemistry for pyridine nucleus as NAD(P)+.

  • NADP depicted as positively charged.

Differences in Roles: NAD vs. NADP

NAD (Nicotinamide Adenine Dinucleotide)

  • Generally used as a cofactor in oxidation reactions (catabolic processes).

    • Catabolic Processes: Include:

      • Lipid oxidation.

      • Carbohydrate oxidation.

    • NAD+ functions as an oxidizing agent in catabolic reactions.

    • Accepts hydrogen atoms/electrons during oxidation.

    • NAD is converted to NADH, which holds energy.

      • reoxidized in the ETC

    • NADH participates in electron transport chain to produce ATP.

NADP (Nicotinamide Adenine Dinucleotide Phosphate)

  • Rarely acts as an oxidizing agent.

  • Primarily association with NADPH, which is involved in synthetic reactions.

  • NADPH is commonly regarded as a reducing agent in anabolic processes (building macromolecules).

FAD and FMN as Flavine Nucleotides

Overview

  • Derived from Vitamin B2 (Riboflavin).

  • Deficiencies can inhibit reactions reliant on FAD or FMN.

Prosthetic Groups vs. Free Cofactors

  • FAD and FMN function as prosthetic groups, covalently attached to their enzymes.

  • NAD and NADP exist as free molecules in cytoplasm, not attached to enzymes.

Structure of FAD and FMN

  • FAD: Flavine adenine dinucleotide, a dinucleotide made of two nucleotides.

    • Structure includes a base component, sugar, and phosphate.

  • FMN: Flavine mononucleotide, a single nucleotide similar to one of the FAD components.

Redox Chemistry of Flavine Nucleotides

  • Flavine nucleotides (FMN and FAD) can participate in one-electron or two-electron oxidations of substrate

    • Hydrogen atoms

    • they are involved in a greater diversity of reactions than the NAD(P)-linked dehydrogenases.

  • NAD/NADP, by contrast, only participate in two-electron oxidations (removing two hydrogen atoms).

  • The fully reduced form of the nucleotides are FADH2 and FMNH2 and when only one electron is accepted they form the stable semiquinone radical forms FADH· and FMNH

Reaction Result: FAD.

  • FAD to FADH2 involves acceptance of two hydrogen atoms during full reduction.

  • Acceptance of both protons leads to FADH2, storing energy for ATP generation.

Importance of B Vitamins and Coenzymes

  • Vitamin B2 deficiency leads to reduced energy production.

  • Coenzymes support metabolic processes and reactions.

Metabolism: Understanding Fat Catabolism

Energy Yield from Biomolecules

Energy Values (in kJ per gram dry weight)

  • Fats yield almost twice the energy of carbohydrates or proteins when oxidized.

  • Fats identified as the most concentrated energy storage in biological systems.

Structural Analysis of Fatty Acids

Reductiveness of Fatty Acids

  • Fatty acids composed primarily of CH2 (methylene) groups, regarded as highly reduced.

  • High reduction states imply higher energy yields when oxidized to CO2.

Fats vs. Carbs/Proteins

  • Carbohydrates have alcohol/hydroxyl groups; hence, are already partially oxidized compared to fats.

Resulting in lesser energy yield per gram when fully oxidized to CO2.

Oxidation States of Carbon

  • Oxidation states defined by the composition of hydrogens and oxygens attached to carbon.

  • Fully oxidized carbon exists as CO2; fully reduced as alkanes (only H attached).

Rate of Energy Release Through Oxidation

Implication on Energy Yield

  • More reduced states (e.g., alkanes) yield more energy upon complete oxidation compared to alcohol or acids.

  • Higher energy extractible from reduced compounds informs metabolic planning during fasting.

Availability of Energy Sources During Fasting

  • Prioritization:

    • Glucose: Immediate source, limited energy.

    • Glycogen: Higher energy reserve, but requires hydrolysis.

    • Proteins: Used in extreme fasting, generally not first choice.

    • Fats: Largest energy reserve, challenging to mobilize.

Lipid Catabolism Overview

Storage Form in Body

  • Fatty acids stored primarily as triglycerides (glycerol + fatty acids).

  • Triglycerides need to be hydrolyzed for energy release.

Fatty Acid Catabolism Stages

Fatty acids are prepared for catabolism by activating
them to fatty acyl CoA

  • Activation happens in two steps

Three Stages of Fatty Acid Oxidation

  1. Beta-Oxidation: Partial breakdown to acetyl-CoA.

  2. Citric Acid Cycle (Krebs Cycle): Oxidation of acetyl-CoA to release CO2.

  3. Electron Transport Chain: Reducing NAD and FAD to generate ATP.

Initial Stage: Beta-Oxidation

  • Involves enzymatic action to cleave fatty acids to generate acetyl-CoA.

  • A cyclic process breaks down fatty acids two carbons at a time.

  • The fatty acyl CoA molecules, once in
    the mitochondrion are committed to
    undergo beta-oxidation.

  • Beta oxidation consists of four steps:

    • oxidation

    • hydration

    • oxidation

    • thiolysis

  • Each pass through beta oxidation removes one acetyl moiety in the form of acetyl-CoA