MYRISTIC ACID

CAS Number:544-63-8 
EC Number:250-924-5

Synonyms:
Acid, Myristic; Acid, Tetradecanoic; Myristate; Myristic Acid; Tetradecanoic Acid; Tetradecanoic acid; MYRISTIC ACID; 544-63-8; n-Tetradecanoic acid; n-Tetradecoic acid; Crodacid; n-Tetradecan-1-oic acid; 1-Tridecanecarboxylic acid; Hydrofol acid 1495; Univol U 316S; Emery 655; Myristinsaeure; Myristate tetradecoic acid; Hystrene 9014; Neo-fat 14; Myristic acid (natural); C14 fatty acid; Myristic acid, pure; n-Myristic acid; Tetradecanoate; acide tetradecanoique; NSC 5028; FEMA No. 2764; CCRIS 4724; CH3-[CH2]12-COOH; HSDB 5686;; C14:0; UNII-0I3V7S25AW; Philacid 1400; CHEBI:28875; AI3-15381; Prifac 2942; EINECS 208-875-2; 1-tetradecanecarboxylic acid; BRN 0508624; 0I3V7S25AW; CHEMBL111077; NSC5028; TUNFSRHWOTWDNC-UHFFFAOYSA-N; Lead dimyristate; DSSTox_CID_1666; n-tetradecan-1-oate;DSSTox_RID_76274; DSSTox_GSID_21666; CAS-544-63-8; Myristic acid [NF]; myristoate; myristoic acid; n-Tetradecanoate 3usx; Myristic acid pure; Myristic Acid Flake; Hystrene 9514; Kortacid 1499; Edenor C 14; Myristic Acid 655;1-Tridecanecarboxylate; Prifrac 2942; Myristic acid, 95%; Myristic acid, natural; tridecanecarboxylic acid; Myristic acid (8CI); 3v2n; 3w9k; Myristic acid, puriss.; ACMC-1AKMJ; 32112-52-0; Tetradecanoic acid (9CI); bmse000737; D08OBF; Epitope ID:176772; C14:0 (Lipid numbers); AC1L1WF8; AC1Q2W1A; SCHEMBL6374; 4-02-00-01126 (Beilstein Handbook Reference); KSC271K5J; MLS002152942; WLN: QV13; Tetradecanoic (Myristic) acid; AC1Q2W11; GTPL2806; DTXSID6021666; CTK1H1554; MolPort-001-779-744; s161; HMS3039E15; HMS3648O20; Myristic acid, analytical standard; tetradecanoic acid (myristic acid); KS-00000JH9; NSC-5028; ZINC1530417; EINECS 250-924-5; Myristic acid >=98.0% (GC); Tox21_201852; Tox21_302781; ANW-32091; BDBM50147581; LMFA01010014; LS-210; MFCD00002744; SBB060024; STL185697; Myristic acid, >=95%, FCC, FG; Myristic acid, Sigma Grade, >=99%; AKOS009156714; DB08231; DS-3833; MCULE-9671122893; NE10225; RTR-019260; NCGC00091068-01; NCGC00091068-02;CGC00256547- 01;NCGC00259401-01; AN-21363; SMR001224536; ST023797; AB1002562; KB-26094; TR-019260; FT-0602832; M0476; ST24025989; EN300-78099; C06424; Myristic acid, Vetec(TM) reagent grade, 98%; SR-01000854525; I04-0252; SR-01000854525-3; W-109088; F8889-5016; EDAE4876-C383-4AD4-A419-10C0550931DB; UNII-13FB83DEYU component TUNFSRHWOTWDNC-UHFFFAOYSA-N; UNII-5U9XZ261ER component TUNFSRHWOTWDNC-UHFFFAOYSA-N; UNII-96GS7P39SN component TUNFSRHWOTWDNC-UHFFFAOYSA-N; UNII-Q8Y7S3B85M component TUNFSRHWOTWDNC-UHFFFAOYSA-N; UNII-79P21R4317 component TUNFSRHWOTWDNC-UHFFFAOYSA-N; Myristic acid, United States Pharmacopeia (USP) Reference Standard; Tetradecanoic acid; 1-Tridecanecarboxylic acid; n-Tetradecanoic acid; Myristic acid, Pharmaceutical Secondary Standard; Certified Reference Material; 45184-05-2; Myristic acid; n-Tetradecanoic acid; n-Tetradecoic acid; Neo-Fat 14; Univol U 316S; 1-Tridecanecarboxylic acid; Crodacid; Emery 655; Hydrofol acid 1495; Hystrene 9014; n-Tetradecan-1-oic acid; Hystrene 9514; Philacid 1400; Prifac 2942; Prifrac 2942; NSC 5028; Tetradecanoic acid (myristic acid); Acide Myristique; Tetradecanoic (Myristic) acid; Myristic a acid (tetradecanoic acid); Tetradecanoic acid (=Myristic acid);n-tetradecanoic acid; n-tetradecoic acid; n-tetradecan-1-oic acid; 1-tridecanecarboxylic acid; 14:0; miristic sit; myrıstıc asit; miristik acid; L'acide myristique; acide myristique; Acide myristique; L'acide tétradécanoïque; Acide tétradécanoïque; Acide tétradécanoïque; Acide n-tétradécanoïque; Acide myristique

MYRISTIC ACID

Myristic acid

Myristic acid[1]
Skeletal formula of myristic acid
Ball-and-stick model of myristic acid
Names
IUPAC name
Tetradecanoic acid
Other names
C14:0 (Lipid numbers)
Identifiers
CAS Number    
544-63-8 ☑
3D model (JSmol)    
Interactive image
ChEBI    
CHEBI:28875 ☒
ChEMBL    
ChEMBL111077 ☒
ChemSpider    
10539 ☒
ECHA InfoCard    100.008.069 Edit this at Wikidata
EC Number    
208-875-2
IUPHAR/BPS    
2806
PubChem CID    
11005
RTECS number    
QH4375000
UNII    
0I3V7S25AW ☒
CompTox Dashboard (EPA)    
DTXSID6021666 Edit this at Wikidata
InChI[show]
SMILES[show]
Properties
Chemical formula    C14H28O2
Molar mass    228.376 g·mol−1
Density    1.03 g/cm3 (−3 °C)[2]
0.99 g/cm3 (24 °C)[3]
0.8622 g/cm3 (54 °C)[4]
Melting point    54.4 °C (129.9 °F; 327.5 K) [9]
Boiling point    326.2 °C (619.2 °F; 599.3 K) at 760 mmHg
250 °C (482 °F; 523 K)
at 100 mmHg[4]
218.3 °C (424.9 °F; 491.4 K)
at 32 mmHg[3]
Solubility in water    13 mg/L (0 °C)
20 mg/L (20 °C)
24 mg/L (30 °C)
33 mg/L (60 °C)[5]
Solubility    Soluble in alcohol, acetates, C6H6, haloalkanes, phenyls, nitros[5]
Solubility in acetone    2.75 g/100 g (0 °C)
15.9 g/100 g (20 °C)
42.5 g/100 g (30 °C)
149 g/100 g (40 °C)[5]
Solubility in benzene    6.95 g/100 g (10 °C)
29.2 g/100 g (20 °C)
87.4 g/100 g (30 °C)
1.29 kg/100 g (50 °C)[5]
Solubility in methanol    2.8 g/100 g (0 °C)
17.3 g/100 g (20 °C)
75 g/100 g (30 °C)
2.67 kg/100 g (50 °C)[5]
Solubility in ethyl acetate    3.4 g/100 g (0 °C)
15.3 g/100 g (20 °C)
44.7 g/100 g (30 °C)
1.35 kg/100 g (40 °C)[5]
Solubility in toluene    0.6 g/100 g (−10 °C)
3.2 g/100 g (0 °C)
30.4 g/100 g (20 °C)
1.35 kg/100 g (50 °C)[5]
log P    6.1[4]
Vapor pressure    0.01 kPa (118 °C)
0.27 kPa (160 °C)[6]
1 kPa (186 °C)[4]
Magnetic susceptibility (χ)    -176·10−6 cm3/mol
Thermal conductivity    0.159 W/m·K (70 °C)
0.151 W/m·K (100 °C)
0.138 W/m·K (160 °C)[7]
Refractive index (nD)    1.4723 (70 °C)[4]
Viscosity    7.2161 cP (60 °C)
3.2173 cP (100 °C)
0.8525 cP (200 °C)
0.3164 cP (300 °C)[8]
Structure
Crystal structure    Monoclinic (−3 °C)[2]
Space group    P21/c[2]
Lattice constant    
a = 31.559 Å, b = 4.9652 Å, c = 9.426 Å[2]
α = 90°, β = 94.432°, γ = 90°
Thermochemistry
Heat capacity (C)    432.01 J/mol·K[4][6]
Std enthalpy of
formation (ΔfH⦵298)    −833.5 kJ/mol[4][6]
Std enthalpy of
combustion (ΔcH⦵298)    8675.9 kJ/mol[6]
Hazards
GHS pictograms    GHS07: Harmful[10]
GHS Signal word    Warning
GHS hazard statements    H315[10]
NFPA 704 (fire diamond)    
[11]
NFPA 704 four-colored diamond
120
Flash point    > 110 °C (230 °F; 383 K) [11]
Lethal dose or concentration (LD, LC):
LD50 (median dose)    >10 g/kg (rats, oral)[11]
Related compounds
Related compounds    Tridecanoic acid, Pentadecanoic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Myristic acid (IUPAC systematic name: 1-tetradecanoic acid) is a common saturated fatty acid with the molecular formula CH3(CH2)12COOH. Its salts and esters are commonly referred to as myristates or tetradecanoates. It is named after the binomial name for nutmeg (Myristica fragrans), from which it was first isolated in 1841 by Lyon Playfair.[12]

Occurrence

Myristica fragrans fruit contains myristic acid
Nutmeg butter has 75% trimyristin, the triglyceride of myristic acid. Besides nutmeg, myristic acid is also found in palm kernel oil, coconut oil, butterfat, 8–14% of bovine milk, and 8.6% of breast milk as well as being a minor component of many other animal fats.[9] It is also found in spermaceti, the crystallized fraction of oil from the sperm whale. It is also found in the rhizomes of the Iris, including Orris root.[13][14] It also comprises 14.49% of the fats from the fruit of the Durian species Durio graveolens.[15]

Uses
See also: Myristoylation
Myristic acid is commonly added to the N-terminus glycine in receptor-associated kinases to confer the membrane localization of the enzyme. The myristic acid has a sufficiently high hydrophobicity to become incorporated into the fatty acyl core of the phospholipid bilayer of the plasma membrane of the eukaryotic cell. In this way, myristic acid acts as a lipid anchor in biomembranes.[16]

Various "human epidemiological studies have shown that myristic acid and lauric acid were the saturated fatty acids most strongly related to the average serum cholesterol concentrations in humans",[17] meaning they were positively correlated with higher cholesterol levels as well as raising triglycerides in plasma by some 20% increasing the risk for cardiovascular disease, although some research points to myristic acid's positive effects on HDL cholesterol and hence improving HDL (good cholesterol) to total cholesterol ratio.[18]

Reduction of myristic acid yields myristyl aldehyde and myristyl alcohol.

Myristic Acid is a saturated long-chain fatty acid with a 14-carbon backbone. Myristic acid is found naturally in palm oil, coconut oil and butter fat.

NCI Thesaurus (NCIt)
Tetradecanoic acid is an oily white crystalline solid. (NTP, 1992)

CAMEO Chemicals
Tetradecanoic acid is a straight-chain, fourteen-carbon, long-chain saturated fatty acid mostly found in milk fat. It has a role as a human metabolite, an EC 3.1.1.1 (carboxylesterase) inhibitor, a Daphnia magna metabolite and an algal metabolite. It is a long-chain fatty acid and a straight-chain saturated fatty acid. It is a conjugate acid of a tetradecanoate.

Molecular Weight of Myristic Acid:    228.37 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
XLogP3    5.3    Computed by XLogP3 3.0 (PubChem release 2019.06.18)
Hydrogen Bond Donor Count of Myristic Acid:    1    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Hydrogen Bond Acceptor Count of Myristic Acid:    2    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Rotatable Bond Count of Myristic Acid:    12    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Exact Mass of Myristic Acid:    228.20893 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
Monoisotopic Mass of Myristic Acid:    228.20893 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
Topological Polar Surface Area     of Myristic Acid:37.3 Ų    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Heavy Atom Count of Myristic Acid:    16    Computed by PubChem
Formal Charge of Myristic Acid:    0    Computed by PubChem
Complexity of Myristic Acid:    155    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Isotope Atom Count of Myristic Acid:    0    Computed by PubChem
Defined Atom Stereocenter Count     of Myristic Acid:0    Computed by PubChem
Undefined Atom Stereocenter Count of Myristic Acid:    0    Computed by PubChem
Defined Bond Stereocenter Count  of Myristic Acid:    0    Computed by PubChem
Undefined Bond Stereocenter Count of Myristic Acid:    0    Computed by PubChem
Covalently-Bonded Unit Count of Myristic Acid:    1    Computed by PubChem
Compound Is Canonicalized  of Myristic Acid:    Yes

Myristic acid
Myristic acid, a long-chain saturated fatty acid (14:0), is one of the most abundant fatty acids in milk fat (above 10%) (Verruck et al., 2019). This fatty acid is known because it accumulates fat in the body, however, its consumption also impacts positively on cardiovascular health. This behavior is largely influenced by the balance between saturated fatty acid and simple dietary carbohydrates in the diet (Ruiz-Núñez, Dijck-Brouwer, & Muskiet, 2016). Myristic acid is directly involved in post-translational protein changes and mechanisms that control important metabolic processes in the human body (Legrand & Rioux, 2015; Ruiz-Núñez et al., 2016). Dabadie, Peuchant, Bernard, Leruyet, and Mendy (2005) reported that moderate myristic acid consumption improves long-chain omega-3 fatty acids levels in plasma phospholipids, which could exert improvement of cardiovascular health parameters in humans. Another research by the same group (Dabadie, Peuchant, Motta, Bernard, & Mendy, 2008) reported that the consumption of myristic acid from dairy fat increased HDL cholesterol and decreased triacylglycerides levels, while no changes in LDL cholesterol were observed. Additional immunomodulatory functions are exerted by myristic acid through the increase of a specific protein involved in activation of macrophages in murine with high levels of myristic acid intake.

Myristic acid

Presence

The fruit of Myristica fragrans contains myristic acid
Nutmeg butter contains 75% trimyristin, the triglyceride of myristic acid. In addition to nutmeg, myristic acid is also found in palm kernel oil, coconut oil, fatty, 8-14% of bovine milk and 8.6% of breast milk as well as being a minor component of many other animal fats. [9] It is also found in spermaceti, the crystallized fraction of sperm whale oil. It is also found in the rhizomes of the Iris, including the Orris root. [13] [14] It also comprises 14.49% of the fat of the fruit of the species Durian Durio graveolens. [15]

Uses
See also: Myristoylation
Myristic acid is commonly added to N-terminal glycine in receptor-associated kinases to confer membrane localization of the enzyme. Myristic acid has sufficiently high hydrophobicity to incorporate into the fatty acyl nucleus of the phospholipid bilayer of the plasma membrane of the cell. eukaryote. In this way, myristic acid acts as a lipid anchor in the biomembranes. [16]

Various "human epidemiological studies have shown that myristic acid and lauric acid were the saturated fatty acids most strongly related to mean serum cholesterol concentrations in humans", [17] which means that they were positively correlated with higher cholesterol levels as well as increased triglycerides in plasma. by about 20%, which increases the risk of cardiovascular disease, although some research indicates the positive effects of myristic acid on HDL cholesterol and therefore an improvement in the ratio of HDL (good cholesterol) to total cholesterol. [18]

Reduction of myristic acid produces myristyl aldehyde and myristyl alcohol.

Tetradecanoic acid, more commonly known as myristic acid, C14: 0, is a 14 carbon saturated fatty acid with the structural formula CH3– (CH2) 12 – COOH. It is found in particular in coconut oil and palm kernel oil, two edible oils particularly rich in lauric acid and myristic acid, the two most hypercholesterolemic saturated fatty acids known.

Like many fatty acids, myristic acid is involved in the composition of the plasma membrane of eukaryotic cells, formed of a lipid bilayer. On the intracellular side of the plasma membrane, myristic acid can interact with proteins; this is called myristoylation. This acid binds covalently to the nitrogen of a glycine residue at position 2 in the polypeptide chain of the protein. This intrinsic protein is then said to be embedded (see also prenylation and palmitylation).

Reduction of myristic acid gives myristyl alcohol.

Myristic acid: new regulatory and signaling functions

Among the most consumed saturated fatty acids in the human diet, myristic acid (linear 14-carbon saturated acid, CH3— [CH2] 12 — COOH, C14: 0) comes in third position, far behind palmitic acid. (CH3— [CH2] 14-COOH, C16: 0) and stearic acid (CH3— [CH2] 16-COOH, C18: 0) [1]. Present in large quantities in milk fat (it represents about 10% of fatty acids), myristic acid mainly occupies the sn-21 [2] position on triglycerides, which ensures effective intestinal absorption in the form of 2 -monoglyceride. In animal cells, myristic acid is relatively rare and represents on average 1% of fatty acids. Its low endogenous biosynthesis (a few hundred µg in the liver) makes its food origin quantitatively predominant (between 4 and 8 g / day) [3]. When added to cultured hepatocytes, myristic acid is predominantly incorporated into cellular lipids (65% of initial C14: 0) but is also largely β-oxidized (30%) (Figure 1) [4].

Figure 1. Figure 1.
The pathways of myristic acid metabolism in the cell. After uptake by the cell or endogenous biosynthesis, the metabolic fate of myristic acid is distributed between incorporation into lipids, β-oxidation and other more minor reactions such as N-terminal myristoylation.
The description of the physiological roles of myristic acid has long been restricted to its responsibility in the increase of plasma cholesterol in humans and animals, when it is provided in excess in the diet [5], which explains its poor nutritional reputation. These results, although questioned since nutritional studies explored the impact of reasonable doses of total saturated fatty acids and myristic acid in particular [6, 7], have largely contributed to mask the other important biological functions of this fatty acid as well as the molecular bases of these functions.

Myristic acid and N-myristoyltransferases
Among the saturated fatty acids (and the unsaturated ones), only myristic acid, after activation in myristoyl-CoA, has the capacity to irreversibly form an amide bond (Figures 1 and 2) with proteins having an amino-terminal end necessarily starting by a Glycine, but from which it is difficult to extract a consensual amino acid sequence [8]. This reaction, called N-terminal myristoylation, is catalyzed by N-myristoyltransferase (NMT), the product of two highly homologous genes identified in animals and encoding two isoforms (NMT1 and NMT2) [9, 10]. The majority of studies have focused on the first and more active of the two isoforms [11]. This has a strong specificity for its myristoyl-CoA substrate [12] (the apparent Km varies between 1 and 100 µm depending on the experimental conditions, the origin of the enzyme, the type of protein co-substrate, etc.) , which is explained by the structure of its catalytic site [13]. The cThe cellular concentration of myristoyl-CoA available for protein acylation is very low, in the order of 5 nM [14]. Only 0.05% of the initial myristic acid (Figure 1) added to cultured hepatocytes is used for N-terminal myristoylation [15]. NMT seems capable of using both exogenous myristic acid [8] and myristic acid resulting from endogenous biosynthesis, when the latter is in sufficient concentration, after elongation from lauric acid or retroconversion of the palmitic acid for example [15, 16]. In the retina, a tissue with a specific fatty acid composition, the bioavailability of the fatty acid substrate appears to be predominant for the acylation of proteins. In fact, 2 rare unsaturated fatty acids with 14 carbons (C14: 1 n-9 and C14: 2 n-6) [17], whose concentration in the form of acyl-CoA is greater in the retina than in the other tissues, can replace myristic acid as a substrate for NMT [18]. The cellular concentration of myristoyl-CoA is therefore an important regulator of the level of myristoylation in the cell.

Figure 2. Figure 2.
N-terminal myristoylation of proteins and biological consequences on myristoylated proteins. N-myristoyltransferases (NMT) catalyze the formation of an amide bond between myristoyl-CoA and a protein having at least one amino-terminal glycine. The myristic acid thus bound allows the protein to either anchor itself to the membrane, or to change subcellular addresses or to interact with other proteins.
Myristoylation is predominantly a co-translational reaction. The amino-terminal glycine of the protein substrate being translated is exposed to NMT after the action of methionyl aminopeptidase which removes the initiating methionine. Recently, post-translational myristoylation has been demonstrated in cells in apoptosis, after cleavage of the protein substrate by caspases, which then exposes an internal site of myristoylation [19].

Myristoylated proteins and the functions of myristoylation
The known myristoylated proteins are key factors of intracellular signaling (α subunit of G proteins, Myristoylated alanine-rich C-kinase substrate or MARCKS, a ubiquitous substrate of protein kinase C, etc.), oncogenes, but also suppressors tumor, viral structural proteins but also common eukaryotic proteins (NADH-cytochrome b5 reductase). We will not detail here the regulations associated with myristoylation which are well documented for these proteins. A predictive bioinformatics study estimated the proportion of myristoylated proteins in the human proteome at 0.5% [20]. Among the some 25,000 proteins derived from genes described after the sequencing of the human genome, around one hundred myristoylated proteins have been identified to date [21]. So there are still a few to be discovered, including those in which myristoylation occurs at a post-translational stage.

The myristoylation of a protein induces important modifications for the myristoylated protein: anchoring to the membrane, interactions with other proteins, change of subcellular addressing (Figure 2). By this route, myristic acid therefore has a specific role in regulating the biological activity of myristoylated proteins. In many models (yeast, Drosophila, mouse), the deletion of the gene encoding NMT has important consequences ranging from developmental alterations to the death of the model [22, 23].

The discovery of N-terminal myristoylation of proteins in eukaryotic animal and plant cells, as well as in viruses, has sparked renewed interest in this fatty acid, and new related regulatory and signaling functions are discovered. , directly or indirectly, to myristoylation. This review will therefore be limited to developing a few recent examples involving myristic acid and / or myristoylation in different cellular regulations.
Myristic acid and regulation of signaling by nitric oxide synthase of endothelial cells (eNOS)
Nitric oxide synthase (NOS) enables the formation of the free radical, nitrogen monoxide (NO), by catalyzing the oxidation of arginine to citrulline [24]. The endothelial enzyme (eNOS), found in the walls of blood vessels, is myristoylated. The first studies of subcellular localization showed that the enzyme is membrane and more specifically located in caveolae [25]. Mutagenesis experiments directed against the myristoylation site showed that in these mutants, the targeting of the protein to the membrane was no longer done and that it then remained exclusively cytosolic [26]. The eNOS protein is also palmitoylated: this double acylation is necessary re to its addressing to the membrane, and depalmitoylation allows the regulation of this addressing [27, 28]. Myristoylation is therefore the major, but not the only, determinant of the anchoring of eNOS in the membrane. This membrane localization could allow a better extracellular release and a more effective vasodilator action of nitric oxide.

Recently, another level of regulation of eNOS by myristic acid has been demonstrated (Figure 3). In the endothelial cell model, myristic acid specifically activates eNOS in a time-dependent (a few minutes), dose-dependent and presence of cAMP [29]. Myristic acid would interact, without proven myristoylation, with the CD36 “garbage collector” receptor, also located in caveolae, and would activate a cascade of reactions [30]. The CD36 receptor could activate AMP kinase, via stimulation of Src kinases, which in turn activates eNOS. Without showing again the specific effect of C14: 0 via CD36 on the production of NO, Isenberg et al. [31] suggest that inhibition of myristic acid uptake by CD36 by the addition of thrombospondin 1 (an endogenous inhibitor of angiogenesis via CD36) results in inhibition of nitric oxide production. They also suggest that exogenous myristic acid captured via CD36 may be specifically directed towards the myristoylation of certain proteins. Indeed, on the same model, the addressing of Fyn (a kinase of the Src family) to the membrane, after its myristoylation, is stopped if the uptake of myristic acid by CD36 is inhibited, even by adding C14: 0 exogenous to the culture medium. These two studies demonstrate that free myristic acid can have a specific action, at low concentrations (between 10 and 50 µM), in the endothelial cell. However, the mechanism is not fully understood as these two studies did not measure the actual impact of myristoylation on eNOS activity using non-myristoylatable mutants of the enzyme, nor the specificity of orientation. from myristic acid captured via CD36 to eNOS myristoylation.

Figure 3. Figure 3.
Mechanisms of activation of endothelial nitric oxide synthase (eNOS) by myristic acid. 1. Nitric oxide (NO) synthase is myristoylated and then delivered to the plasma membrane [25]. Recently, it was shown that myristic acid could interact with the CD36 receptor and activate eNOS via Src and AMP kinases. Myristic acid captured by CD36 could also be specifically dedicated to the myristoylation of eNOS. 2. This capture is inhibited by thrombospondin-1 (TSP1). 3. On the other hand, when provided in esterified form in HDL, myristic acid inhibits the activating effect of estrogen on eNOS activity by inhibiting the association of the enzyme with calmodulin (Cal) . SR-BI: Class B and Type I scavenger receiver.
In addition, it appears that myristic acid may have an important role in the known action of estradiol on eNOS activity. Indeed, it has been shown that estradiol, transported by HDL (high density lipoproteins), was able to specifically activate eNOS [32]. However, this activation is no longer found in diabetic patients. However, compared to control HDLs, the only significant difference between HDLs isolated in diabetics is their composition, since they contain 3 to 4 times more myristic acid [33]. HDL from healthy patients supplemented with C14: 0 have an identical inhibitory effect on eNOS activity (Figure 3). This new regulation by myristic acid appears to involve the inhibition of the association between eNOS and calmodulin (the major intracellular calcium receptor). These studies demonstrate the importance of the transport vector (albumin complex or HDL) and the delivery form (unesterified fatty acid or triglycerides) of myristic acid for the regulation of eNOS.
Myristic acid and regulation of the bioavailability of polyunsaturated fatty acids
It is well accepted that an increase in the cellular content of polyunsaturated fatty acids of the ω3 family (omega 3), and in particular of the longer derivatives (eicosapentaenoic acids or EPA, and docosahexaenoic or DHA), is beneficial for prevention of cardiovascular diseases and more generally for human health [34, 35]. Strategies for increasing ω3 content by diets enriched in myristic acid have been evaluated after observing the activating effect of myristic acid on Δ6-desaturase [36]. This enzyme is involved in the biosynthesis of very long chain polyunsaturated fatty acids of the ω6 and ω3 family, by introducing a double bond on the linoleic (C18: 2 n-6) and α-linolenic (C18: 3) precursors. n-3) (Figure 4). In vivo, in rats fed for 2 months on diets containing increasing doses of myristic acid that, the concentration of α-linolenic acid precursor increases in all tissues in a dose-dependent manner, and very long-chain derivatives of the ω3 family, including EPA and DHA, increase in the brain and red blood cells. [37, 38]. Myristic acid and α-linolenic acid are both substrates of β-oxidation. Preferential β-oxidation of myristic acid appears to spare that of α-linolenic acid. This precursor sparing effect probably adds to the activating effect of myristic acid on the biosynthesis of highly unsaturated derivatives. In humans, a diet with a moderate intake of myristic acid (1.2% of total energy), compared to a diet with a lower intake (0.6%), also increases the levels of DHA and d 'EPA in plasma phospholipids and DHA levels in plasma cholesterol esters [39]. The molecular mechanism behind C14: 0 activation of Δ6-desaturase in the cell model is not identified, but the hypothesis of myristoylation of the enzyme, which has an amino glycine. terminal, has recently been ruled out [40]. Another protein of the Δ6-desaturant complex, NADH-cytochrome b5 reductase, on the other hand, is myristoylated and its level of myristoylation could therefore be a regulatory parameter.