Enzymatic pathway of archaeal lipid biosynthesis

In eukaryotes, enzymes of different subcellular compartments participate in the assembly of membrane lipids. As a consequence, interorganelle lipid transfer is extensive in growing cells. A prominent example is the transfer of membrane lipid precursors between the endoplasmic reticulum (ER) and the photosynthetic thylakoid membranes in plants. Mono- and digalactolipids are typical photosynthetic membrane lipids. In Arabidopsis, they are derived from one of two pathways, either synthesized de novo in the plastid, or precursors are imported from the ER, giving rise to distinct molecular species. Employing a high-throughput robotic screening procedure generating arrays of spot chromatograms, mutants of Arabidopsis were isolated, which accumulated unusual trigalactolipids. In one allelic mutant subclass, trigalactosyldiacylglycerol1, the primary defect caused a disruption in the biosynthesis of ER-derived thylakoid lipids. Secondarily, a processive galactosyltransferase was activated, leading to the accumulation of oligogalactolipids. Mutations in a permease-like protein of the outer chloroplastic envelope are responsible for the primary biochemical defect. It is proposed that this protein is part of a lipid transfer complex.

for the biosynthesis of membrane lipids.

Formation of Bacterial Glycerol-Based Membrane Lipids: Pathways, Enzymes, ..

membrane phospholipid biosynthesis.

AB - In eukaryotes, enzymes of different subcellular compartments participate in the assembly of membrane lipids. As a consequence, interorganelle lipid transfer is extensive in growing cells. A prominent example is the transfer of membrane lipid precursors between the endoplasmic reticulum (ER) and the photosynthetic thylakoid membranes in plants. Mono- and digalactolipids are typical photosynthetic membrane lipids. In Arabidopsis, they are derived from one of two pathways, either synthesized de novo in the plastid, or precursors are imported from the ER, giving rise to distinct molecular species. Employing a high-throughput robotic screening procedure generating arrays of spot chromatograms, mutants of Arabidopsis were isolated, which accumulated unusual trigalactolipids. In one allelic mutant subclass, trigalactosyldiacylglycerol1, the primary defect caused a disruption in the biosynthesis of ER-derived thylakoid lipids. Secondarily, a processive galactosyltransferase was activated, leading to the accumulation of oligogalactolipids. Mutations in a permease-like protein of the outer chloroplastic envelope are responsible for the primary biochemical defect. It is proposed that this protein is part of a lipid transfer complex.

acid biosynthesis pathway for the development of ..

During the progression of Mycoplasma hominis cultures from the early logarithmic phase to the stationary phase of growth, the total phospholipid content of the cell membranes decreased. Measurement of the amount of the various phospholipids during the growth cycle showed that a decrease in the phosphatidylglycerol (PG) content, accompanied by an increase in the phosphatidic acid content, occurred upon aging of the culture. Pulse labeling experiments revealed that the PG, once formed, is relatively stable, undergoing no detectable turnover in growing cultures of M. hominis. No changes in the fatty acid composition of the membrane phospholipids were observed on aging of the culture, with palmitic acid predominating throughout the growth cycle. The preferential incorporation of palmitate into the phospholipid fraction is apparently caused by the higher activity of the membrane-bound acyl-coenzyme A (CoA):alpha-glycerophosphate transacylase with palmityl-CoA rather than with oleyl-CoA as substrate. The activity of the soluble acyl-CoA synthetase was the same whether palmitate or oleate served as substate. M. hominis membrane preparations contained a PG-synthetase system catalyzing the incorporation of L-alpha-glycerol-3-phosphate into PG. The activity of the PG synthetase system was markedly dependent on the age of the culture, being highest in cells from the early exponential phase of growth while declining sharply thereafter, and thus probably responsible, in part, for the decrease in PG content upon aging of the cells. Electron paramagnetic resonance spectra of a spin-labeled fatty acid incorporated in M. hominis membranes revealed a marked decrease in the freedom of motion of the spin label on aging of the culture. It is proposed that this decrease is due primarily to the decrease in the lipid-to-protein ratio of the membranes and has a marked effect on the activity of membrane-associated enzymes and transport systems.

05/10/2016 · The enzymes responsible for the biosynthesis of ..
and that inhibition of different enzymes within the FA biosynthesis pathway can ..

The end products of cholesterol utilization are the bile acids

1961, 83, 3080) made the first total synthesis of arachidonic acid.

Imai J demonstrated that the oxidative desaturation of a saturated fatty acid (palmitic acid) is depressed in diabetic rats ().

Kennedy EP described the general pathways of the glycerolipid biosynthesis in animal cells ().

Bremer J et al.

Phospholipid Biosynthesis ..

Important dates in the history of lipids ..

Membranes are barriers for hydrophilic molecules and ions because of the hydrophobic core of the phospholipid bilayer. A membrane or is a two-dimensional, spherical particle separating an inside compartment from an outside compartment. In addition to lipids, a membrane contains that control the transport of hydrophilic and charged, small and large molecules into and out of the cell and intracellular organelles. The importance of the lipid bilayer membrane is its ability to function as an . This enables charge separation and thus the storage of electro-chemical energy in form of ion gradients. One example is the proton motif force (pmf or proton gradient) discussed in sections on oxidative phosphorylation and photosynthesis. Membrane proteins that serve as conductors are used by the cell to extract small quanta of this energy for synthesis or signaling mechanisms. Two examples are ATP synthesis and action potentials, respectively.

Dec 15, 1984 · Regulation of membrane-bound enzymes of glycosphingolipid biosynthesis

Cytochrome P450 enzymes in drug metabolism: Regulation …

AB - Mycolic acids are the major lipid components of the unique mycobacterial cell wall responsible for the protection of the tuberculosis bacilli from many outside threats. Mycolic acids are synthesized in the cytoplasm and transported to the outer membrane as trehalose-containing glycolipids before being esterified to the arabinogalactan portion of the cell wall and outer membrane glycolipids. The large size of these unique fatty acids is a result of a huge metabolic investment that has been evolutionarily conserved, indicating the importance of these lipids to the mycobacterial cellular survival. There are many key enzymes involved in the mycolic acid biosynthetic pathway, including fatty acid synthesis (KasA, KasB, MabA, InhA, HadABC), mycolic acid modifying enzymes (SAM-dependent methyltransferases, aNAT), fatty acid activating and condensing enzymes (FadD32, Acc, Pks13), transporters (MmpL3) and tranferases (Antigen 85A-C) all of which are excellent potential drug targets. Not surprisingly, in recent years many new compounds have been reported to inhibit specific portions of this pathway, discovered through both phenotypic screening and target enzyme screening. In this review, we analyze the new and emerging inhibitors of this pathway discovered in the post-genomic era of tuberculosis drug discovery, several of which show great promise as selective tuberculosis therapeutics.