All cells need fatty acids for membrane lipids. Fat cells make large amounts of fat (triacyl-glycerols) in times of plenty. The basic machinery is a multienzyme complex (in bacteria) or a multidomain protein (in eukaryotes) that uses the substrate acetyl-CoA. In both cases the growing fatty acid chain is not released: it swivels from enzyme to enzyme or domain to domain in the array, adding two carbons for each complete cycle until the limiting length of 16 carbons is reached: The product, palmitic acid, is then released. Although the reactions look similar (Fig. 13.12), the process is not a reversal of j oxidation (page 290). It uses entirely different enzymes, takes place in the cytosol rather than in the mitochondria, and is separately regulated. Like much of biosynthesis it is reductive, and the reducing power comes not from NADH but from the closely related dinucleotide NADPH.
Initially acetyl-CoA is carboxylated to malonyl-CoA. From here on, however, fatty acid synthesis does not use free coenzyme A to carry the growing chain but instead uses a protein called acyl carrier protein (ACP). The malonyl residue is transferred to ACP from malonyl-CoA. This condenses with a molecule of acetyl-ACP (made from an acetyl-CoA) to give a four-carbon molecule with the release of ACP and CO2. The four-carbon acetoacetyl-ACP is next reduced to hydroxybutyryl-ACP. The next enzyme (molecule or domain) removes water, leaving a double bond, which is again reduced to give butyryl-CoA. Another malonyl-CoA is condensed with this and the cycle continues. Finally a chain 16 carbons long has been made (palmitic acid). At this point it is hydrolyzed from the ACP. Overall 14 NADPH molecules, 1 acetyl-CoA, and 7 malonyl-CoA molecules have been used to make palmitic acid. Palmitic acid is then used by enzymes on the endoplasmic reticulum that extend the chains and that can introduce double bonds. Mammals cannot, however, synthesize all the different kinds of fatty acids that they need for their membranes and must obtain essential fatty acids in food (page 42).
The main use of fatty acids is to make glycerides, both triacylglycerols for storage in fat globules and phospholipids for membranes. The process uses glycerol phosphate, which is usually generated by reduction of dihydroxyacetone phosphate. The fatty acid is then swopped in, replacing the phosphate group, which leaves as inorganic phosphate.
Glycerol phosphate, the building block from which lipids and phospholipids are made, is obtained in most cells by reducing dihydroxyacetone phosphate. This in turn is generated in the glycolytic pathway. This means that adipose cells can only make fats when glucose is abundant—when we are eating lots of sugar or carbohydrate. In contrast, liver cells have an enzyme called glycerol kinase that phosphorylates glycerol to make glycerol phosphate directly, so that some lipids and phospholipids can be made even during times of fasting.
Nitrogen is an important constituent of proteins and nucleic acids and many other molecules important in cells. Although nitrogen gas is plentiful, making up 80% of the atmosphere, it is inert. It is chemically a very difficult task to break the triple bond and reduce nitrogen gas to ammonia that can be used for incorporation into biomolecules. Chemical fertilizers are made using the Haber process, which fixes nitrogen by the use of pressures of around
Eating Well, Getting Fat
Eating Well, Getting Fat
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