FCH 532 Lecture 27 Chapter 26: Essential amino acids Quiz Wed: NIH Shift Quiz Mon: Essential amino acids Exam 3: Next Wed.

Table 26-2 Essential and Nonessential Amino Acids in Humans. Page 1030

Glutamate is the precursor for Proline, Ornithine, and Arginine E. coli pathway from Gln to ornithine and Arg involves ATP-driven reduction of the glutamate gamma carboxyl group to an aldehyde (N-acetylglutamate-5-semialdehyde). Spontaneous cyclization is prevented by acetylation of amino group by N-acetylglutamate synthase. N-acetylglutamate-5-semialdehyde is converted to amine by transamination. Hydrolysis of protecting group yields ornithine which can be converted to arginine. In humans it is direct from glutamate-5-semialdehyde to ornithine by ornithine--aminotransferase

Arginine synthesis glutamyl kinase 6. Acetylglutamate kinase N-acetyl--glutamyl phosphate dehydrogense N-acetylornithine--aminotransferase Acetylornithine deacetylase ornithine--aminotransferase Urea cycle to arginine Page 1036

Conversion of 3-phosphoglycerate’s 2-OH group to a ketone Figure 26-58 The conversion of glycolytic intermediate 3-phosphoglycerate to serine. Conversion of 3-phosphoglycerate’s 2-OH group to a ketone Transamination of 3-phosphohydroxypyruvate to 3-phosphoserine Hydrolysis of phosphoserine to make Ser. Page 1037

Serine is the precursor for Gly Ser can act in glycine synthesis in two ways: Direct conversion of serine to glycine by hydroxymethyl transferase in reverse (also yields N5, N10-methylene-THF) Condensation of the N5, N10-methylene-THF with CO2 and NH4+ by the glycine cleavage system

Cys derived from Ser In animals, Cys is derived from Ser and homocysteine (breakdown product of Met). The -SH group is derived from Met, so Cys can be considered essential.

Methionine adenosyltransferase Methyltransferase Adenosylhomocysteinase Methionine synthase (B12) Cystathionine -synthase (PLP) Cystathionine -synthase (PLP) -ketoacid dehydrogenase Propionyl-CoA carboxylase (biotin) Methylmalonyl-CoA racemase Methylmalonyl-CoA mutase Glycine cleavage system or serine hydroxymethyltransferase N5,N10-methylene-tetrahydrofolate reductase (coenzyme B12 and FAD) Page 1002

Cys derived from Ser In plants and microorganisms, Cys is synthesized from Ser in two step reaction. Reaction 1: activation of Ser -OH group by converting to O-acetylserine. Reaction 2: displacement of the acetate by sulfide. Sulfide is derived fro man 8-electron reduction reaction.

Figure 26-59a. Cysteine biosynthesis Figure 26-59a Cysteine biosynthesis. (a) The synthesis of cysteine from serine in plants and microorganisms. Page 1038

Sulfite to sulfide by sulfite reductase Figure 26-59b Cysteine biosynthesis. (b) The 8-electron reduction of sulfate to sulfide in E. coli. Sulfate activation by ATP sulfuylase and adeosine-5’-phosphosulfate (APS) kinase Sulfate reduced to sulfite by 3’-phosphoadenosine-5’-phosphosulfate (PAPS) reductase Sulfite to sulfide by sulfite reductase Page 1038

Biosynthesis of essential amino acids Pathways only present in microorganisms and plants. Derived from metabolic precursors. Usually involve more steps than nonessential amino acids.

Biosynthesis of Lys, Met, Thr First reaction is catalyzed by aspartokinase which converts aspartate to apartyl--phosphate. Each pathway is independently controlled.

Figure 26-60 The biosynthesis of the “aspartate family” of amino acids: lysine, methionine, and threonine. Page 1039

Figure 26-61 The biosynthesis of the “pyruvate family” of amino acids: isoleucine, leucine, and valine. Page 1040

Figure 26-62 The biosynthesis of chorismate, the aromatic amino acid precursor. Page 1042

Figure 26-63 The biosynthesis of phenylalanine, tryptophan, and tyrosine from chorismate. Page 1043

Figure 26-64 A ribbon diagram of the bifunctional enzyme tryptophan synthase from S. typhimurium Page 1044

Figure 26-65 The biosynthesis of histidine. Page 1045