Compound lipid synthesis

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

Malate is not the only form in which C4 compounds are exported from mitochondria. Much oxaloacetate is combined with acetyl-CoA to form citrate the latter leaves the mitochondria and is cleaved by the ATP-dependent citrate-cleaving enzymes (Eq. 13-39). This, in effect, exports both acetyl-CoA (needed for lipid synthesis) and oxaloacetate which is reduced to malate within the cytoplasm. Alternatively, oxaloacetate may be transaminated to aspartate. The aspartate, after leaving the mitochondria, may be converted in another transamination reaction back to oxaloacetate. All of these are part of the nonequilibrium process by which C4 compounds diffuse out of the mitochondria before completing the reaction sequence of Eq. 17-46 and entering into other metabolic processes. Note that the reaction of Eq. 17-46 leads to the export of reducing equivalents from mitochondria, the opposite of the process catalyzed by the malate-aspartate shuttle which is discussed in Chapter 18 (Fig. 18-18). The two processes are presumably active under different conditions. 

Phospholipids are ideal compounds for making membranes because of their amphipathic nature (see chapter 17). The polar head-groups of phospholipids prefer an aqueous environment, whereas the nonpolar acyl substituents do not. As a result, phospholipids spontaneously form bilayer structures (see fig. 17.6), which are a dominant feature of most membranes. The phospholipid bilayer is the barrier of the cell membrane that prevents the unrestricted transport of most molecules other than water into the cell. Entry of other molecules is allowed if a specific transport protein is present in the cell membrane. Similarly, the phospholipid bilayer prevents leakage of metabolites from the cell. The amphipathic nature of phospholipids has a great influence on the mode of their biosynthesis. Thus, most of the reactions involved in lipid synthesis occur on the surface of membrane structures catalyzed by enzymes that are themselves amphipathic. 

The stratum corneum basically contains a mixture of cholesterol, free fatty acids, and ceramides, placed in multilayers. They mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Studies have shown that each of the three key lipid classes is required for normal barrier function (32). These reports also show the potential of certain inhibitors of lipid synthesis to enhance the trans-dermal delivery of drugs like lido-caine or caffeine. Thus, the modulation of stratum corneum lipids is an important determinant of the barrier permeability to both hydrophobic and hydrophilic compounds transport and drug penetration. It has been reported that an inverse correlation exists between solute penetration and stratum corneum lipid content (33). 

The enantiomeric composition of 3-hydroxyacid esters in passion fruit, mango and pineapple have been investigated. Figure VII presents the separation of (R)- and (S)-3-hydroxybutanoates. The compounds in yellow passion fruit were mainly of the (S)-(+)-configuration as predicted for intermediates of B-oxidation. In the purple variety, and in mango, the (R)-(-)-enantiomers predominate. These compounds may be found as an offshoot of de novo lipid synthesis or by hydration of (Z)-2-enoyl-CoA leading to (R)-(-)-3-hydroxyacyl-CoA (1 2) ... 

If a rapidly growing photosynthetic cell such as an alga cell is exposed to C 02 for 1 to 2 minutes and then killed, as much as 30% of the radioactive compounds formed behave as lipidlike substances when partitioned between aqueous and organic solvents. A considerable portion of the chloroplast structure consists of lipid materials, and rapid lipid synthesis is required for chloroplast growth and division. 

Camps, F., and Guerrero, A.. (1999) Synthesis of Long-Chain Compounds with Conjugated Unsaturation, in Lipids Synthesis and Manitfacture (Gunstone, F.D., ed.) pp. 46-93, Sheffield Academic Press, Sheffield, UK. 

Lipid biosynthesis occurs in two stages (1) fatty acid synthesis, and (2) incorporation of fatty acids into triglycerides or compound lipids. 

In a previous section (Section V,B) instances have been cited where lipids may act as covalently bound intermediates in the biosynthesis of polysaccharides. The possible involvement of lipids in protein biosynthesis has also been briefly mentioned (Section IV,B), although in no case is there definitive evidence on this point. It is of interest that there are certain similarities in the general metabolic behavior of proteins and lipids. Under conditions of active growth both the proteins (Mandelstam, 1958) and the major lipid of E. coli, phosphatidylethanolamine (Kanfer and Kennedy, 1963), undergo little or no turnover. Furthermore, under resting cell conditions, where little net protein synthesis occurs, the synthesis of lipids is greatly reduced (Tarlov and Kennedy, 1965). A study of the inhibition of protein and lipid synthesis in protoplasts by various antibiotics has revealed that there is no differential inhibitory effect on either class of compounds a... 

---