Squalene Synthesis (FDFT1) Analysis

As a pivotal research direction in dermatology, squalene holds vast promise in skincare and therapeutic interventions. Creative Biolabs is dedicated to offering comprehensive squalene-related products and services, contributing to our clients' endeavors in basic research or preclinical assessments.

Squalene: Key to Skin Health

Squalene, an unsaturated hydrocarbon precursor of sterols, composed of six isoprene units, stands as a crucial step in cholesterol biosynthesis. It constitutes a significant component of skin surface lipids, alongside other lipids, forming a major part of sebum.

• Structure of Squalene

Squalene is a non-cyclic triterpene consisting of six isoprene units, with all six double bonds in a trans configuration, rendering it highly unstable and prone to oxidation.

• Synthesis and Sources of Squalene

Squalene in the body primarily derives from two sources: dietary intake and endogenous synthesis. Squalene synthase (farnesyl diphosphate farnesyl transferase 1; FDFT1) catalyzes the conversion of two molecules of farnesyl diphosphate (FPP) into pre squalene diphosphate, which further converts into squalene through a two-step reaction, and can subsequently transform into cholesterol and other sterols.

Fig.2 Squalene synthesis.²

• Distribution of Squalene

Upon ingestion or synthesis, a portion of squalene binds to very low-density lipoproteins, widely distributed in tissues or organs such as adipose tissue, skin, lymph nodes, and liver. Another portion undergoes demethylation and chemical bond rearrangement to eventually form cholesterol.

• Primary Functions of Squalene

As a long and highly unsaturated hydrocarbon compound, squalene serves as a natural lubricant with high permeability. Its main functions include:

1. Skin Protection: Participating in the formation of skin surface lipids, squalene acts as a protective barrier, preventing external stimuli and moisture loss, maintaining skin hydration and softness.
2. Cholesterol Synthesis: Squalene is a crucial precursor in cholesterol biosynthesis, as the enzymatic conversion of FPP to squalene by squalene synthase is the first step in cholesterol biosynthesis.
3. Antioxidant: Squalene and its oxidation products have certain protective effects against ultraviolet radiation and possess antioxidant properties, reducing damage caused by free radicals to the skin.
4. Hypoxia Tolerance: Studies indicate that mice fed with squalene can survive longer under conditions of acute cerebral ischemic hypoxia.

Fig.3 Gene structure of FDFT1.³

Squalene and Diseases

As a vital constituent of the skin, squalene plays a crucial role in maintaining skin health. Abnormalities in its function or content are associated with many diseases.

• Squalene synthase deficiency syndrome (SQSD): A rare congenital defect in cholesterol biosynthesis, SQSD clinical features include facial dysmorphia, neonatal seizures, or intellectual disabilities.
• Acne Vulgaris: As a major component of skin maintenance and barrier protection, Squalene has been found in higher concentrations in sebum in acne vulgaris-afflicted skin.
• Hypercholesterolemia: Squalene and squalene synthase play important roles in the cholesterol biosynthesis pathway, with data demonstrating their involvement in the pathophysiology of certain hypercholesterolemia conditions.
• Skin Pigmentation: Squalene secreted by sebaceous glands can be oxidized by oxygen radicals released by porphyrins to form peroxysqualene, which may contribute to melanin deposition.

Fig.4 Isoprenoid/cholesterol biosynthesis by squalene.⁴

Our Services

As a leading entity in the biosciences domain, Creative Biolabs is committed to providing squalene-related services based on cutting-edge scientific research and looks forward to amalgamating it with the burgeoning field of stem cell research. Our services will focus on delivering tailored solutions to our clients, including synthesis, analysis, and mechanism exploration, aiding in a deeper understanding of its potential applications in skin care and disease intervention. Please do not hesitate to contact us for robust support.

References

1. Condro, Sciortino, et al. " Squalene peroxidation and biophysical parameters in acne-prone skin: a pilot "in vivo" study." Pharmaceuticals 16 (2023): 1704.
2. Grande, Gorinstein, et al. " Plant sources, extraction methods, and uses of squalene." International Journal of Agronomy. 10 (2018): 1829160.
3. Do, Kiss, et al. " Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway." Clin. Genet. 75 (2009): 19-29.
4. Coman, Vissers, et al. " Squalene synthase deficiency: clinical, biochemical, and molecular characterization of a defect in cholesterol biosynthesis." The American Journal of Human Genetics 103 (2018): 125-130.

For Research Use Only. Not For Clinical Use.