Eukaryotes fatty acid biosynthesis

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

Not only eukaryotic cells but also bacteria have successfully been targeted by PNA anhsense strategies. Thus it has been shown that PNA complementary to ribosomal RNA or mRNA encoding an essential fatty acid biosynthesis protein, effectively kills E. coli. Furthermore, it has been shown that PNA directed to the start codon of the y -lactamase gene re-sensitized otherwise resistant E. coli to the antibiohc ampiciUin [64—66]. Conjugating a simple transporter peptide to the PNA increased the potency significantly, and an even more potent antibacterial PNA... 

In eukaryotes, anabolic and catabolic pathways that interconvert common products may take place in specific subcellular compartments. For example, many of the enzymes that degrade proteins and polysaccharides reside inside organelles called lysosomes. Similarly, fatty acid biosynthesis occurs in the cytosol, whereas fatty... 

In prokaryotes, each of the reactions of fatty acid synthesis is catalyzed by a separate enzyme. However, in eukaryotes, the enzymes of the fatty acid synthesis elongation cycle are present in a single polypeptide chain, multifunctional enzyme complex, called fatty acid synthase. The fatty acid synthase complex exists as a dimer, with the ACP moiety shuttling the fatty acyl chain between successive catalytic sites, and from one subunit of the dimer to the other. It is, in effect, a highly efficient production line for fatty acid biosynthesis. 

During fatty acid biosynthesis, the eukaryotic cell requires a lot of acetyl-CoA. Where does the cell get most of the required acetyl-CoA ... 

Fatty acid biosynthesis is similar in all known prokaryotes and eukaryotes. In eukaryotes, the biosynthesis of a fatty acid such as palmitate (Cl6) occurs in the cytoplasm. The basic strategy includes the following three possible steps ... 

Contrast the enzymatic machinery for fatty acid biosynthesis in bacteria with that in eukaryotes. Outline the movements of the elongating acyl chain on the mammalian/atty acid synthetase dimer during fatty acid biosynthesis. 

In eukaryotes and prokaryotes, ACCase is a key enzyme in fatty acid biosynthesis [1]. The reaction product, malonyl-CoA, is both an intermediate in the de novo synthesis of primary fatty acids and also a substrate in the formation of long-chain fatty acids and flavonoids in plants [2, 3]. Aryloxyphenoxypropionates (APPs) and cyclohexandiones (CHDs) are two chemical classes of molecules that selectively inhibit homomeric, chloroplastic ACCase from grasses [4, 5], which makes them post emergent herbicides used worldwide to control grassy weeds. 

Introduction Primary Fatty Acids Fatty Acids of Plant Vegetative Parts Biosynthesis Fatty Acid Biosynthesis The Two-Pathway Model of Lipid Biosynthesis The Second 3-Ketoacyl ACP Synthase Isozyme Biosynthesis of Unsaturated Fatty Acids The Prokaryotic Pathway The Eukaryotic Pathway Biosynthesis of Triacylglycerides Degradation of Fatty Acids Unusual Fatty Acids in Plants Fatty Acids from Unusual Starter Units Fatty Acids with Unusual Patterns of Unsaturation Hydroxy Fatty Acids Epoxy Fatty Acids... 

Acetyl-CoA carboxylase (ACCase) catalyzes the ATP dependent carboxylation of acetyl-CoA to form malonyl-CoA. This reaction is the first committed step in fatty acid biosynthesis and is a potentially rate-limiting step in the process. Two forms of ACCase have been observed - a prokaryotic and a eukaryotic form. In the prokaryotic form, the biotin carboxylase, biotin carboxyl carrier protein and carboxyl transferase components of ACCase are associated with different polypeptides in a multi-subunit (MS) complex (Samols et al. 1988). In contrast, the eukaryotic form comprises multimers of a single multifunctional (MF) polypeptide of200 kDa. Dicots have been reported to have an MS plastidial ACCase and an MF extra-plastidial ACCase while grasses and other monocots are believed to have the MF ACCase in both plastids and extra-plastidial sources (Sasaki et al. 1995). 

In plants, de novo fatty acid biosynthesis occurs exclusively in the stroma of plastids, whereas, with the exception of plastidial desaturation, modification of fatty acid residues including further desaturation and triacylglrycerol (TAG) assembly are localized in the cytosol/endoplasmic reticulum (ER). The primary fatty acids formed in the plastid (palmitic, stearic, and oleic acid) are used in the plastidic prokaryotic pathway for membrane lipid synthesis or diverted to the cytoplasmic eukaryotic pathway for the synthesis of membrane lipids or storage TAGs (1). Movement of glycerolipids is believed to occur in the reverse direction between the cytosol/ER and the plastids in the highly regulated manner (2). 

I A GENERAL FRAME FOR THE STUDY OF POLYUNSATURATED FATTY ACID BIOSYNTHESIS IN PLANTS THE PROKARYOTIC AND EUKARYOTIC PATHWAYS [3-7 ]. 

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

Still another difference between biosynthesis of fatty acids and oxidation (in mammals) is that the former has an absolute requirement for NADPH (Fig. 17-12) while the latter requires NAD+ and flavo-proteins (Fig. 17-1). This fact, together with many other observations, has led to the generalization that biosynthetic reduction reactions usually require NADPH rather than NADH. Many measurements have shown that in the cytosol of eukaryotic cells the ratio [NADPH]/[NADP+] is high, whereas the ratio [NADH]/[NAD+] is low. Thus, the NAD+/NADH system is kept highly oxidized, in line with the role of NAD+ as a principal biochemical oxidant, while the NADP+/NADPH system is kept reduced. 

Biosynthesis of Polyunsaturated Fatty Acids Occurs Mainly in Eukaryotes... 

As mentioned in chapter 17, unsaturated fatty acids are abundant in all living organisms. Alternative mechanisms for the biosynthesis of unsaturated fatty acids have evolved. Two chemically distinct pathways exist for the introduction of a cis double bond into saturated fatty acids The anaero-bic pathway as typified in E. coli, and the aerobic pathway found in eukaryotes. 

Uttaro, A.D. Biosynthesis of polyunsaturated fatty acids in lower eukaryotes. lUBMB Life, 58 (2006) 563-571. 

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