Vitamins and Coenzymes

Vitamins

Organic micronutrients, required in small daily amounts

• most are essential nutrients (humans can’t synthesize the basic form of the vitamin

• Have to be chemically modified to their final structure in our bodies

• The absence(and sometimes excess) of certain vitamins can cause disease

• The active form of many water-soluble vitamins are also known as coenzymes

Two major classes of vitamins

• Water soluble: B vitamins(most B vitamins are coenzymes), Vitamin C

• Fat Soluble: A, D, E, K

What is the primary biochemical role of B complex vitamins in cellular metabolism, and what happens in their absence?

They act as coenzyme precursors.

• With them: Coenzymes bind to enzymes to complete the active site, allowing substrates to bind and reactions to proceed instantaneously (by donating/accepting electrons, atoms, or functional groups).

• Without them: Substrates cannot respond to or bind effectively to their enzymes, stalling the pathway

Conceptually, how does the Vitamin B complex bridge macronutrient degradation and ATP generation?

They serve as required coenzymes at every major crossroads converting proteins, carbohydrates (sugars), and fats into energy.

Specifically, they are heavily concentrated in:

1. The conversion of substrates into Pyruvic acid and Acetyl-CoA.

2. Running the Citric Acid Cycle (specifically requiring B1​, B2​, Niacin, and Pantothenic acid to drive the cycle and release energy).

Vitamin B1

Thiamin

• Active coenzyme form of thiamin is thiamin pyrophosphate (TPP)

• Formed by addition of 2 phosphate groups by the enzyme thiamine pyrophosphate transferase

• 2 ring system: a pyrimidine and thiazole

Thiamin Functions

TPP is a coenzyme for enzymes that perform decarboxylation(removal of carboxyl group) and transkeletalation (transfer of two carbon units)

Thiamine Mechanism

1. Loss Proton: Forms a reactive carbanion.

2. Attack Substrate: Carbanion attacks the substrate's carbonyl carbon.

3. Form Adduct: Creates a tetrahedral adduct.

4. Decarboxylate: TPP acts as an electron sink to drive decarboxylation.

5. Stabilize: Intermediate carbanion is stabilized via resonance.

• Note: TPP is NOT covalently bound to the enzyme.

What are the three key enzyme complexes that require Thiamin (Vit B1​) as a cofactor, and what pathways do they connect?

Thiamin acts as thiamin pyrophosphate for:

1. Pyruvate Dehydrogenase: Converts Pyruvate → Acetyl-CoA (links Glycolysis to the Citric Acid Cycle).

2. α-Ketoglutarate Dehydrogenase: Converts α-Ketoglutarate → Succinyl-CoA (in the Citric Acid Cycle).

3. Transketolase: Functions in the Hexose/Pentose Phosphate Pathway (links Glucose-6-P to Ribulose-5-P/Fructose-6-P).

Vitamin B2

Riboflavin

• active forms are the coenzymes FAD and flavin adenine FMN

• Critical for numerous metabolic pathways, including the ETC

• FMN and FAD can accept either one or two electrons, allowing then to act in redox reactions

FAD vs FMN

• FAD(Flavin adenine dinucleotide): more complex, make up of riboflavin sugar , phosphate group, and adenine nucleotide, can carry two electrons

• FMN(Flavin mononucleotide): simple, made up of Riboflavin sugar and phosphate group, carries one electron

• FAD and FMN are coenzymes for a wide variety of enzymes, often called flavoenzymes, that are involved in redox reactions, or oxidation-reduction, in metabolic pathways such as the citric acid cycle (TCA) and electron transport

Vitamin B3

Niacin

• NADH: Used in cellular respiration to produce ATP via oxidative phosphorylation. It is produced in glycolysis and the Krebs cycle and is used in the electron transport chain

• NADPH: Used in anabolic redox reactions

• Both NADH and NADPH are essential for the cellular metabolism and play crucial roles in the energy production and carbon assimilation processes

Vitamin B5

Pantothenic Acid

• Energy metabolism: pantothenic acid is essential for converting carbohydrates, proteins, and fats into energy

• It is a precursor to coenzyme A (CoA), which is vital for fatty acid metabolism and the TCA cycle, a key energy-producing process

  • Thiol group → site where acetyl group is added to make CoA

• Also essential for the synthesis of fatty acids, phospholipids, steroid hormones, hemoglobin heme, and acetylcholine

Vitamin B6

Pyridoxine

• 3 Different forms: pyridoxal, pyridoxine, and pyridoxamine

• can all be converted to coenzyme pyridoxal phosphate

Vit B6 - Pyridoxal Phosphate Functions

• Amino acid and fatty acid metabolism

• conversion of tryptophan to niacin or serotonin

• synthesis of heme

• Coenzyme bound through Schiff base

What are the key chemical intermediates and steps in the PLP-dependent transamination mechanism (Glutamate: Aspartate Aminotransferase)?

The reaction follows a "ping-pong" mechanism in two halves:

Phase 1: Amino Acid → α-Keto Acid

1. Enzyme Activation: PLP is initially bound to the enzyme via a Lysine residue (Schiff base).

2. Aldimine Formation: The incoming amino acid replaces Lysine to form an Aldimine intermediate.

3. Ketimine Formation: A proton shift converts the Aldimine into a Ketimine.

4. Release: Water hydrolyzes the Ketimine, releasing the first α-keto acid and leaving the enzyme temporarily modified as Pyridoxamine phosphate (PMP).

Phase 2: The Reverse (PMP → PLP)

• A new α-keto acid binds to PMP and runs the exact steps in reverse (Ketimine → Aldimine) to release a new amino acid and regenerate the original E-PLP complex.

Vitamin B7

Biotin

• functions as a cofactor that aids in the transfer of CO₂ groups in important metabolic pathways such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism.

What four enzymes host biotin as a prothetic group

1. Pyruvate Carboxylase (oxaloacetate from pyruvate)

2. Beta-Methylcrotonyl-CoA carboxylase

3. Propionyl-CoA carboxylase

4. Acetyl-CoA carboxylase