@mikewick77: SkO CoQ10 Coenzyme

RAGE gene (Receptor for Advanced Glycation End-products) senolytics SkQ SkQ1 (Visomitin) plastoquinone plastoquinol quinone peroxyl radical of cardiolipin lipid antioxidant lipophilic cation Ubiquinol ubiquinone coenzyme Q10 PQQ CoQ10

SkQ is a synthetic molecule designed by joining a plastoquinone molecule (derived from plants) to a positively charged triphenylphosphonium (TPP) ion.

Quinones: Redox-active benzoquinones that can be reduced to hydroquinones (quinols). They are capable of acting as free radical scavengers and chain-breaking antioxidants.

Triphenylphosphonium (TPP) Ion: A lipophilic cation. It can pass easily through phospholipid bilayers, and its positive charge causes it to accumulate several hundred-fold in the mitochondrial matrix due to the inner membrane potential.

Linker: An alkyl chain (e.g., decyl, C10) that connects the quinone to the TPP moiety.

Function: Plastoquinone, usually found in chloroplasts, is highly effective at acting as a "rechargeable" antioxidant when delivered to mitochondria.

Mechanism of Action

Once TPP-conjugated quinones accumulate within the mitochondria, they undergo the following cycle:

Reduction: The quinone is reduced to a quinol (active antioxidant) by the electron transport chain (mainly Complex I/II).

Scavenging: The quinol reacts with free radicals (lipid peroxyl radicals), neutralizing them and becoming oxidized back to the quinone form.

Recycling: The oxidized quinone is reduced again by the electron transport chain.

MitoNAC (Mito-N-Acetylcysteine): A compound linking N-acetylcysteine (NAC), an antioxidant precursor, to a triphenylphosphonium cation.

MitoQ and SkQ rely on a positive charge to cross the membrane and accumulate in the negatively charged mitochondria.

Electron & Positive Charge: The Q-cycle involves the 2-electron oxidation of ubiquinol (reduced form) and reduction of ubiquinone (oxidized form).

Ubiquinol acts as a chain-breaking antioxidant.

The shikimate pathway converts sugar-acids (PEP and E4P) into chorismate, the essential precursor for aromatic amino acids (phenylalanine, tyrosine, tryptophan) and various secondary metabolites, including quinones.

quinone shikimate pathway aromatic amino acids sugar-acids chorismate

NAD⁺ Quinone Vitamin K2

The shikimate pathway is a 7-step metabolic route in plants, fungi, and microbes that converts sugar-acids (E4P) and carboxylic acids (PEP) into chorismate, the precursor to aromatic amino acids (phenylalanine, tyrosine, tryptophan) and various metabolites, including quinones (ubiquinone). It originates from glucose via glycolysis and the pentose phosphate pathway.

Key Details of the Shikimate Pathway

Starting Materials: The pathway begins with the condensation of Phosphoenolpyruvate (PEP), a carboxylic acid from glycolysis, and Erythrose 4-phosphate (E4P) from the pentose phosphate pathway.

Major Intermediate: Shikimate is a key intermediate that, through a series of steps, is converted into chorismate.

Core Function: Produces the aromatic amino acids (AAAs) phenylalanine, tyrosine, and tryptophan, which are essential for protein synthesis, lignin, and secondary metabolites.

Quinones and Other Compounds: Beyond amino acids, the pathway provides precursors for naphthoquinones, ubiquinone-10 (coenzyme Q10), and folates.

Significance: Because the shikimate pathway is absent in animals, it is a key target for herbicides (glyphosate) and antimicrobial agents.

Key Metabolite Relationships

Glucose: Provides the carbon backbone for both PEP and E4P.

Chorismate: The final common product, acting as a branch point for aromatic amino acids and quinones.

Sugar-acids/Carboxylic Acids: Intermediates like shikimic acid (a sugar-acid derivative) and quinic acid are produced within this pathway, with shikimic acid serving as a raw material for pharmaceutical synthesis.

sugar-acids glucose carboxylic acid monoterpenoid phenol hydroxybenzoic shikimic chorismic chorismate mevalonic synthesis

The biosynthesis of aromatic compounds, including hydroxybenzoic acids and various phenols, primarily occurs through the shikimic acid pathway, which originates from sugar metabolism. This pathway converts glucose-derived precursors into essential aromatic amino acids (phenylalanine, tyrosine, tryptophan) and phenolic secondary metabolites.

Core Synthesis Pathways

Shikimic Acid Pathway: This seven-step process begins with the condensation of phosphoenolpyruvate (PEP, from glycolysis) and erythrose-4-phosphate (E4P, from the pentose phosphate pathway) to form 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP).

Chorismic Acid (Chorismate): This is the final product of the shikimate pathway and serves as a major branch point for synthesizing phenylalanine, tyrosine, tryptophan, and diverse phenolic compounds.

Mevalonic Acid Pathway (MVA): While the shikimate pathway produces aromatic rings, the MVA pathway (and the MEP pathway) produces terpenes, which can combine with phenolic shikimate derivatives to form complex structures like prenylated phenols.

Synthesis of Specific Compounds

Hydroxybenzoic Acids (C6-C1): These are produced via branch points in the shikimate pathway (from 3-dehydroshikimic acid) or from hydroxycinnamic acids produced in the phenylpropanoid pathway. Important examples include p-hydroxybenzoic acid, gallic acid, and vanillic acid.

Phenols & Phenolic Acids: Shikimic acid is converted into chorismic acid, which is then converted into prephenic acid and eventually phenylalanine or tyrosine. These amino acids are precursors to phenylpropanoids (C6-C3), such as flavonoids and lignans, which act as defense mechanisms in plants.

Monoterpenoid Phenols: These are typically formed by combining phenolic structures (from the shikimate pathway) with monoterpenes (derived from the mevalonic/MEP pathway), often under stress conditions.

Sugar-Acids & Related Compounds: Quinic acid and gallic acid are often produced in the pathway as side products, used by plants for storage or defense.

Key Metabolic Roles
Shikimate Pathway Regulation: It is essential for producing aromatic compounds in bacteria, fungi, and plants, but is absent in mammals.

Metabolic Engineering: Glucose is used in microbial fermentation to high-yield production of shikimic acid, p-hydroxybenzoic acid, and other aromatic precursors for industrial use, such as the synthesis of Tamiflu (oseltamivir) from shikimic acid.

Yellow Oil / Lipophilic Substance: Coenzyme Q and its early, smaller precursors are often described as yellow-orange lipophilic (fat-soluble) materials.

Coenzyme Q Precursors and Biosynthesis

4-Hydroxybenzoate (4-HB): The primary and canonical precursor of the benzoquinone ring in all organisms. In mammals, 4-HB is derived from tyrosine or phenylalanine.

Alternative Precursors (Natural Products):

Kaempferol and Resveratrol: A flavonoid that acts as an efficient precursor in mammalian (specifically kidney) cells, directly increasing CoQ levels.

@mikewick77: SkO CoQ10 Coenzyme | Ecency