Amino Acid Synthesis Essential Amino Acids : amino acids that cannot be synthesized by the organism at a rate sufficient to meet the normal requirements of growth, reproduction, and normal maintenance and therefore must be supplied by the diet Non-Essential Amino Acids : amino acids that can be made from simpler precursors and are thus not required in the diet Essential Amino Acids Non Essential Amino Acids Arginine Alanine Histidine Asparagine Isoleucine Aspartate Leucine Cysteine Lysine Glutamate Methionine Glutamine Phenylalanine Glycine Threonine Proline Tryptophan Serine Valine Tyrosine Willmore 2003

Synthesis of Alanine, Aspartate, Glutamate, Asparagine, and Glutamine Willmore 2003 Synthesis of Alanine, Aspartate, Glutamate, Asparagine, and Glutamine

Synthesis of Alanine, Aspartate, Glutamate, Asparagine, and Glutamine : pyruvate, oxaloacetate, and a-ketoglutarate are all a-keto acids : synthesis of alanine, aspartate, and glutamate is a one-step transamination reaction : asparagine and glutamine synthesized from aspartate and glutamate respectively by an ATP-dependent amidation process : synthesis of glutamine depends upon the formation of a g-glutamylphosphate intermediate Willmore 2003

Synthesis of Arginine, Ornithine, and Proline Willmore 2003

Synthesis of Arginine, Ornithine, and Proline : glutamate family of amino acids : conversion of glutamate to proline involves the reduction of the g-carboxyl group to an aldehyde followed by the formation of an internal Schiff base whose further reduction yields proline : initiated by phosphorylation of glutamate by g-glutamyl kinase : glutamate-5-semialdehyde cyclizes spontaneously to form the internal Schiff base Δ1-pyrroline-5-carboxylate : transamination of semialdehyde to produce ornithine : ornithine converted to arginine via the urea cycle Willmore 2003

Synthesis of Serine Willmore 2003

Synthesis of Serine, Cysteine, and Glycine : serine, cysteine, and glycine are synthesized from 3-phosphoglycerate (an intermediate of glycolysis) : one transamination followed by a hydrolysis of a phosphate group : homocysteine a breakdown product of methionine : cysteine synthesized from serine and homocysteine serine + homocysteine  cystathionine  cysteine + a-ketobutyrate Willmore 2003

Synthesis of Lysine, Methionine, and Threonine Willmore 2003

Synthesis of Lysine, Methionine, and Threonine : synthesis of lysine, methionine and threonine all begins with aspartate : methionine synthesis depends upon the donation of a methyl group by N5-methyl -THF to homocysteine (similar to reverse of cysteine synthesis) : methionine synthase  coenzyme B12 associated enzyme (the only one in mammals besides methylmalonyl-CoA mutase : high levels of homocysteine in the blood  risk factor in cardiovascular disease (including foliate in the diet, vitamin precursor to THF, alleviates this condition Willmore 2003

Synthesis of Valine, Leucine, and Isoleucine TPP + Willmore 2003

Synthesis of Valine, Leucine, and Isoleucine : pyruvate as the starting reactant : first step in isoleucine biosynthesis is thiamine pyrophosphate-dependent : final steps of synthesis dependent upon glutamate : valine aminotransferase catalyzes BOTH valine and isoleucine biosynthesis while leucine depends upon leucine aminotransferase Willmore 2003

Synthesis of Tyrosine, Phenylalanine, and Tryptophan Willmore 2003

Synthesis of Tyrosine, Phenylalanine, and Tryptophan : precursors for the synthesis of tyrosine, phenylalanine, and tryptophan are 1) phosphoenolpyruvate (PEP)  intermediate of glycolysis 2) erythrose-4-phosphate  intermediate of the pentose phosphate pathway : 2-keto-3-deoxy-D-arabinoheptulosonate-7-phosphate (C7 compound) cyclizes to form chorismate (precursor for the benzene rings of R groups) : last two steps of tryptophan synthesis catalyzed by a and b subunits of tryptophan synthase respectively (two different active sites) : substrate tunnelling (channeling)  increases the rate of a metabolic pathway 1) prevents the loss of intermediate product 2) prevents side reactions (or degradation) of intermediate product Willmore 2003

Synthesis of Histidine Willmore 2003

Synthesis of Histidine : histidine derived from 5-phosphoribosyl-a-pyrophosphate (PRPP), a phospho- sugar intermediate involved in the biosynthesis of purines and pyrimidine nucleotides : biosynthesis of a histidine from a purine  RNA WORLD??? - hypothesis that life was originally RNA-based - RNA has catalytic properties - histidine  found in many enzyme active sites  participate in catalytic reactions  nucleophiles and general acid-base catalysis - suggests proteins evolved as more efficient catalysts from RNA catalysts Willmore 2003