Polyprenol

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Polyprenol
Polyprenol.svg
Identifiers
ChemSpider
  • none
Properties
H-(C5H8)n-OH
AppearanceTransparent oily liquid
Density 0.902–0.905 g/cm3
Insoluble
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Polyprenols are natural long-chain isoprenoid alcohols of the general formula H-(C5H8)n-OH, where n is the number of isoprene units. Any prenol with more than 4 isoprene units is a polyprenol. Polyprenols play an important function, acting as natural bioregulators and are found in small quantities in various plant tissues. Dolichols, which are found in all living creatures, including humans, are their 2,3-dihydro derivatives. [1]

Contents

Sources

Live trees are known to contain polyprenols. The needles of conifer trees are one of the richest sources of polyprenols. [2] They are also present in shiitake mushrooms in trace amounts. [3]

Research

Polyprenols have been studied for more than 30 years. Interest has been strongest in Russia, Europe, Japan, India, and the United States. In the early 1930s, a scientific team at the Forest Technical Academy in St. Petersburg, Russia led by Fyodor Solodky, the founder of Forest Biochemistry, and Asney Agranet, began research into the composition of conifer tree needles. [4] They were intrigued by the trees' ability to remain disease free in extremes of temperature ± 40 °C. Development of Solodky's research led Russian scientists to isolate a completely different class of organic substance from the needles, including polyprenols.

Functions

Polyprenols are low molecular natural bioregulators (physiologically active), playing a significant modulating role in the cellular process in plants referred to as biosynthesis.

What polyprenols are to plants, dolichols are to all living creatures, including man. They are in fact of a very similar chemical composition. Dolichols are a derivative of polyprenols with a saturated isoprene unit.

Through dolichols, the dolichol phosphate cycle occurs. The dolichol phosphate cycle plays a major role in the synthesis of glycoproteins.

All proteins from secretions, membranes and intracellular glycoproteins form the basis for the building of membrane receptors which are used in the production of insulin, adrenaline, estrogen, testosterone and other hormones and enzymes. Seemingly, dolichols have an important role in maintenance of the correct lipid composition of membranes. Decreased levels of dolichols have been connected to higher levels of peroxidation of lipids. [5]


The dolichol phosphate cycle facilitates the process of cellular membrane glycosylation, that is, the synthesis of glycoproteins that control the interactions of cells, support the immune system and the stabilization of protein molecules. Out of all these glycoproteins, polyglycoprotein has been found to create drug resistance to multiple cancer treatments and keep cancer cells alive. [6]

The pharmacological activity of polyprenols takes place in the liver, where they are metabolized into dolichols. [7]

Potential medical applications

The interest in polyprenols and dolichols is associated with their wide range of demonstrated biological activity and extremely low toxicity.

Polyprenols cellular reparation and spermatogenesis, and have antistress, adaptogenic, antiulcerogenic and wound-healing activity. [8] Dolichols have antioxidant activity and protect cell membranes from peroxidation. [9] Experiments on mice have demonstrated that polyprenols have antiviral activity, in particular against influenza viruses. [10] It has been established that the dolichol level in liver tumor cells are reduced in comparison with healthy hepatic cells. [11]

The Australian pharmaceutical company Solagran Limited has been investigating the medical significance of polyprenols. [12] [13]

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol, or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">Lipid</span> Substance of biological origin that is soluble in nonpolar solvents

Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes. Lipids have applications in the cosmetic and food industries, and in nanotechnology.

<span class="mw-page-title-main">Lipid-anchored protein</span> Membrane protein

Lipid-anchored proteins are proteins located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane. These proteins insert and assume a place in the bilayer structure of the membrane alongside the similar fatty acid tails. The lipid-anchored protein can be located on either side of the cell membrane. Thus, the lipid serves to anchor the protein to the cell membrane. They are a type of proteolipids.

A congenital disorder of glycosylation is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants. The most common sub-type is PMM2-CDG where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

Dolichol refers to any of a group of long-chain mostly unsaturated organic compounds that are made up of varying numbers of isoprene units terminating in an α-saturated isoprenoid group, containing an alcohol functional group.

<span class="mw-page-title-main">Phosphatidylinositol</span> Signaling molecule

Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule.

<span class="mw-page-title-main">Glycerophospholipid</span> Class of lipids

Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes in eukaryotic cells. They are a type of lipid, of which its composition affects membrane structure and properties. Two major classes are known: those for bacteria and eukaryotes and a separate family for archaea.

Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most bacteria. The name "cardiolipin" is derived from the fact that it was first found in animal hearts. It was first isolated from the beef heart in the early 1940s by Mary C. Pangborn. In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane, where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.

<span class="mw-page-title-main">Ether lipid</span>

In biochemistry, an ether lipid refers to any lipid in which the lipid "tail" group is attached to the glycerol backbone via an ether bond at any position. In contrast, conventional glycerophospholipids and triglycerides are triesters. Structural types include:

<span class="mw-page-title-main">Ceramide</span> Family of waxy lipid molecules

Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.

<span class="mw-page-title-main">Prenol</span> Chemical compound

Prenol, or 3-methyl-2-buten-1-ol, is a natural alcohol. It is one of the most simple terpenoids. It is a clear colorless oil that is reasonably soluble in water and miscible with most common organic solvents. It has a fruity odor and is used occasionally in perfumery.

<span class="mw-page-title-main">Glycosyltransferase</span> Class of enzymes

Glycosyltransferases are enzymes that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar to a nucleophilic glycosyl acceptor molecule, the nucleophile of which can be oxygen- carbon-, nitrogen-, or sulfur-based.

<span class="mw-page-title-main">Phosphatidylglycerol</span> Lipid

Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant and in the plasma membrane where it directly activates lipid-gated ion channels.

<span class="mw-page-title-main">Diphosphomevalonate decarboxylase</span> InterPro Family

Diphosphomevalonate decarboxylase (EC 4.1.1.33), most commonly referred to in scientific literature as mevalonate diphosphate decarboxylase, is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">DPAGT1</span> Protein-coding gene in the species Homo sapiens

UDP-N-acetylglucosamine—dolichyl-phosphate N-acetylglucosaminephosphotransferase is an enzyme that in humans is encoded by the DPAGT1 gene.

<span class="mw-page-title-main">Bactoprenol</span> Chemical compound

Bactoprenol also known as dolichol-11 and C55-isoprenyl alcohol (C55-OH) is a lipid first identified in certain species of lactobacilli. It is a hydrophobic alcohol that plays a key role in the growth of cell walls (peptidoglycan) in Gram-positive bacteria.

<i>N</i>-linked glycosylation Attachment of an oligosaccharide to a nitrogen atom

N-linked glycosylation, is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom, in a process called N-glycosylation, studied in biochemistry. The resulting protein is called an N-linked glycan, or simply an N-glycan.

Ditrans,polycis-polyprenyl diphosphate synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate:isopentenyl-diphosphate cistransferase . This enzyme catalyses the following chemical reaction

Phosphoglycosyl transferase C (PglC) is an enzyme belonging to a class known as monotopic phosphoglycosyl transferases (PGT). PGTs are required for the synthesis of glycoconjugates on the membrane surface of bacteria. Glycoconjugates, such as glycoproteins, are imperative for bacterial communication as well as host cell interactions between prokaryotic and eukaryotic cells lending to bacteria's pathogenicity.

References

  1. Rezanka T, Vortuba J (2001). "Chromatography of long chain alcohols (polyprenols) from animal and plant sources". J. Chromatogr. A. 936 (1–2): 95–110. doi:10.1016/S0021-9673(01)01152-9. PMID   11761009.
  2. Kazimierczak B.; Hertel J.; Swiezewska E.; et al. (1997). "On the specific pattern of long chain polyprenols in green needles of Pinus mugo Turra". Acta Biochim. Pol. 44 (4): 803–808. PMID   9584863.
  3. Wojtas, M; Bieñkowski, T; Tateyama, S; Sagami, H; Chojnacki, T; Danikiewicz, W; Swiezewska, E (2004). "Polyisoprenoid alcohols from the mushroom Lentinus edodes". Chemistry and Physics of Lipids. 130 (2): 109–115. doi:10.1016/j.chemphyslip.2004.02.007. PMID   15172827.
  4. "Science of Polyprenols – Siberian Polyprenols" . Retrieved 2024-04-23.
  5. Cavallini, Gabriella; Sgarbossa, Antonella; Parentini, Ilaria; Bizzarri, Ranieri; Donati, Alessio; Lenci, Francesco; Bergamini, Ettore (April 2016). "Dolichol: A Component of the Cellular Antioxidant Machinery". Lipids. 51 (4): 477–486. doi:10.1007/s11745-016-4137-x. hdl: 11568/794017 . ISSN   1558-9307. PMID   26968401.
  6. Pilotto Heming C, Muriithi W, Wanjiku Macharia L, Niemeyer Filho P, Moura-Neto V, Aran V. P-glycoprotein and cancer: what do we currently know? Heliyon. 2022 Oct 22;8(10):e11171. doi: 10.1016/j.heliyon.2022.e11171. PMID: 36325145; PMCID: PMC9618987.
  7. Chojnacki T.; Dallner G.J. (1983). "The uptake of dietary polyprenols and their modification to active dolichols by the rat liver". J. Biol. Chem. 258 (2): 916–922. PMID   6401722.
  8. Roschin V.I. Chemical composition of lipid fraction of green pine and spruce needles. In edition Study and application of therapeutic-prophylactic medications based on natural biologically active compounds. Edited by V.G. Bespalov and V.B. Nekrasova, SPb. Eskulap, 2000, pp.114-116
  9. Bergamini E.; Bizzarri R.; Cavallini G.; et al. (2004). "Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes?". J. Alzheimer's Dis. 6: 129–135.
  10. Safatov A.S.; Boldyrev A.N.; Bulychev L.E.; et al. (2005). "A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols". J. Aerosol. Med. 18 (1): 55–62. doi:10.1089/jam.2005.18.55. PMID   15741774.
  11. Eggens I.; Elmberger P.G. (1990). "Studies of the polyisoprenoid composition in hepatocellular carcinomas and its correlation with their differentiation". APMIS. 98 (6): 535–542. doi:10.1111/j.1699-0463.1990.tb01068.x. PMID   2166541.
  12. "Company Announcement" (PDF) (Press release). Solagram Limited. 20 September 2005.
  13. "Company Announcement" (PDF) (Press release). Solagram Limited. 21 February 2007.