26.6 Synthesisof Amino Acids 797 dized to carbon dioxide in the citric acid cycle. Moreover, by forming oxaloacetate and a-ketoglutarate from glucogenic amino acids, cells can replenish or increase the concentrations of intermediates of the citric acid cycle. An increase in these intermediates enables cells to step up energy production. You may recall that oxaloacetate for the citric acid cycle can come from severalplaces in metabolism. We have seen that the carboxyla- tion of pyruvatein gluconeogenesisis one of those places.Nowwe seethat amino acid metabolism is another. Certainemergencies such as diabetesor starvationresult in a reduction in the amount of acetyl CoA in the liver. Liver cells respond by using acetyl CoA produced in amino acid metabolism to make ketone bodies. The ketone bodies are transported to other tissues,where they are oxidized for energyproduction. S5mthesis of glycogen and triglycerldes From our study of glucose metabolism, we know that glucose is formed from pyruvate by gluconeogenesis,in which oxaloacetateis an intermedi- ate (seeSec. 24.8). The cell does not recognizewhether the pyruvate has come from glucose or from amino acid metabolism. Once glucose has been synthesized,it can be assembledinto glycogenand stored in muscle or liver cells.Oxaloacetate from amino acid metabolism also can be con- verted to glucosein gluconeogenesis. Fatty acids, as we have seen, are synthesized from acetyl CoA. The acetyl CoA can come from glucose metabolism, from fatty acid metabolism, or from amino acid metabolism. Newly synthesized fatty acids are either used immediately for energy production or converted to triglycerides or membrane lipids. The triglycerides are stored in adipose tissue as an energy reserve. Humans cannot synthesize glucose from acetyl CoA, since people lack the enzyme that converts acetyl CoA to pyruvate. 26,6 Synthesisof omino ocids AIM: Toshow the relotionship betweenthe citric ocid cycleond the synthesisof nonessentialomino ocids. Our bodies need to synthesizenonessential amino acids (seeSec. 21.6) becausetheir proportions in our diet seldom match our bodies' needs.The Slmthesis of 7 of the 12 main starting materials for this qmthesis are pyruvate and two intermedi- nonessential amino acids is ates of the citric acid cycle: a-ketoglutarate and oxaloacetate.As we have simple. seen, cr-ketoglutarateaccepts amino groups from other amino acids in transamination to give glutamic acid, and arginine is formed in the urea Most animal proteins have a cycle. TWo other nonessential amino acids-aspartic acid and alanine- higher nutritional value than may be qmthesized directly from cr-ketoacidsbecause the reactions cat- vegetableproteins becausethey alyzed by the transaminases are reversible. Reversalsof transamination havemore essentialamino acids. reactions form alanine from pyruvic acid and aspartic acid from 794 CHAPTER26 Metabolismof NitrogenCompounds oxaloacetic acid. oo o iltl II CH3-C-C-OH + Glutamic acid ;---- CH3CH-C-OH * a-Ketoglutarate I NHz Pyruvic acid Alanine o oo oo il illl il HO-C-CH2-C-C-OH + Glutamic acid ;- HO-C-CH2CH-C-OH + d-Ketoglutarate I NH, Oxaloaceticacid Asparticacid Glutamineand asparagineareformed from glutamic acid and aspartic acid by reaction of the side-chain carboxyl groups with ammonia. oooo ilililil HO-C-CH2CH-C-OH + NH3 -------HzN-C-CH2CH-C-OH + HzO rl NHz NHz Aspartic acid Asparagine o o o o II HO-C-CH2CH2CH-C-OH + NH3 + HrN-C-CH2CH2CH-C-OH + H2O I NHz NHz Glutamicacid Glutamine Tyrosine,the only nonessential amino acid with an aromatic side chain, is produced from the essential amino acid phenylalanine. The conversion requires a single oxidation step catalyzed by the enzyme phenylalanine hydroxylase. Phenylalanine -cu-co2H -!try: ( }.crt to{ fcu,-ctt-co2H \\//t-"\\//l NH, NH, Phenylalanine Tyrosine So far we have seen how 7 of the 12 nonessential amino acids are syn- thesized. The syntheses of the remaining S-cysteine, histidine, glycine, proline, and serine-are more complex. Their synthesiswill not be consid- ered here. The qmtheses of 4 of the nonessential amino acids from oxaloac- etate and a-ketoglutarate, two intermediates in the citric acid cycle, demonstrate an important metabolic principle: Besidesbeing a pathway of catabolism, the citric acid rycle is a pathway of anabolism-a metabolic switch-hitter..