The Synthesis of Milk Medium-Chain Fatty Acids in Mammary Gland

Zhu, Jiangjiang; Luo, Jun

doi:10.5772/67694

Cited by 2 publications

(2 citation statements)

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“…De novo fatty acid biosynthesis in mammals is catalyzed by the mammalian fatty acid synthase (mFAS) , enzyme. mFAS is a homodimeric multi-enzyme that mainly produces palmitic acid, which is a major component of cell membranes and human breast milk , but also synthesizes myristic and stearic acids, although in smaller proportions. mFAS overexpression was detected in several tumors such as breast cancer, ovarian cancer, prostate cancer, and lung cancer. ,− Consequently, mFAS has become an important drug target for the treatment of human cancer. − …”

Section: Introductionmentioning

confidence: 99%

Complexities of the Reaction Mechanisms of CC Double Bond Reduction in Mammalian Fatty Acid Synthase Studied with Quantum Mechanics/Molecular Mechanics Calculations

2019

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Mammalian fatty acid synthase is a mega-enzyme responsible for de novo fatty acid biosynthesis. NADPH-dependent enoyl reductase (ER) is one of its seven different catalytic domains. The “classical” reduction mechanism of CC bonds catalysed by ER is postulated to take place through a hydride plus proton transfer to the substrate double bond. This mechanism was recently challenged because of the very unexpected experimental detection of two NADPH-substrate covalent adducts (A2 and A4) in enzymes similar to mammalian ER (mER). The fact that 16% of known enzymes used NADPH as a cofactor, mostly as a hydride donor, makes the discovery of previously unknown cofactor-substrate covalent intermediates very interesting. We studied the mechanism of reaction of ER using quantum mechanics/molecular mechanics (QM/MM) calculations, using three layers, two of them described by QM [the very accurate DLPNO-CCSD(T)/CBS and B3LYP/6-311+G(2d,2p)]. The rate-limiting step of the classical pathway was the formation of an enolate intermediate upon hydride transfer (ΔG ‡ of 14.7 kcal·mol–1, which is in very good agreement with the experimental value). Two alternative pathways, considering the recently detected A2 and A4 intermediates, were subsequently studied. The barriers for forming A2-wild type and A4-mutant (17.0 and 19.3 kcal·mol–1) also agreed very well with the experimental values. However, these species were incapable of forming the final product because of the very high Gibbs energy barriers to do so (>70 and >50 kcal·mol–1). They proved to be dead-end branches on the Gibbs energy surface, in chemical equilibrium with the intermediate enolate of the classical pathway. In summary, the classical reaction mechanism seems to hold in mER, but the discovery of unprecedented mechanistic hypotheses challenges the solidity and thoroughness with which we define and explore enzyme reaction mechanisms.

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Section: Introductionmentioning

confidence: 99%

Complexities of the Reaction Mechanisms of CC Double Bond Reduction in Mammalian Fatty Acid Synthase Studied with Quantum Mechanics/Molecular Mechanics Calculations

2019

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“…The FA variety is linked to their multiple physiological roles [ 2 , 7 , 8 ]. Apart from their primary role as energy sources, fats additionally act as biomolecules involved in various processes such as brain development, the function of the immune system, and the integrity of the cellular membranes [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Omega-3 Enrichment on the Chemical Composition and the Pathogenic Microbiota of Ovine Milk

Tzora

Voidarou

Giannenas

et al. 2022

Foods

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The demand for ovine milk and ovine dairy products is constantly increasing due to their exceptional sensorial characteristics and their health benefits for consumers. However, dairy fat content and composition are of particular concern for consumers as well as the medical community, as there are risk factors for coronary disease, diabetes mellitus, cancer, and other serious diseases. For this reason, attempts have been made to control/regulate the fat composition of ovine milk by modifying sheep dietary intake of polyunsaturated fatty acids. In this experimental trial, a group of sheep were fed for 30 days a diet enriched in flaxseeds and lupines, feed ingredients rich in omega-3 fatty acids, aiming to investigate the effects on fat composition and the microbiota of ovine milk. Chemical analysis of the collected milk showed that the omega-3 and omega-6 content was increased. On the opposite, the atherogenic and thrombogenic indexes decreased. Of importance was the semi-protective effect on the udder by the increased omega-3 dietary intake, as depicted by its impact on the biodiversity of the pathogenic microbiota. These findings suggest that ovine milk could be modified under specific conditions to be more appropriate for the consumption by people belonging to high-risk groups for various diseases.

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The Synthesis of Milk Medium-Chain Fatty Acids in Mammary Gland

Cited by 2 publications

References 35 publications

Complexities of the Reaction Mechanisms of CC Double Bond Reduction in Mammalian Fatty Acid Synthase Studied with Quantum Mechanics/Molecular Mechanics Calculations

Complexities of the Reaction Mechanisms of CC Double Bond Reduction in Mammalian Fatty Acid Synthase Studied with Quantum Mechanics/Molecular Mechanics Calculations

Effects of Dietary Omega-3 Enrichment on the Chemical Composition and the Pathogenic Microbiota of Ovine Milk

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