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

2. Table 26-2 Essential and Nonessential Amino Acids in Humans.
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3. 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

4. Arginine synthesis glutamyl kinase 6. Acetylglutamate kinase
N-acetyl--glutamyl phosphate dehydrogense
N-acetylornithine--aminotransferase
Acetylornithine deacetylase
ornithine--aminotransferase
Urea cycle to arginine
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5. Conversion of 3-phosphoglycerate’s 2-OH group to a ketone
Figure 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.
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6. 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

7. 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.

8. 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)
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9. 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.

10. Figure 26-59a. Cysteine biosynthesis
Figure 26-59a Cysteine biosynthesis. (a) The synthesis of cysteine from serine in plants and microorganisms.
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11. 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
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12. Biosynthesis of essential amino acids
Pathways only present in microorganisms and plants.
Derived from metabolic precursors.
Usually involve more steps than nonessential amino acids.

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

14. Figure The biosynthesis of the “aspartate family” of amino acids: lysine, methionine, and threonine.
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15. Figure The biosynthesis of the “pyruvate family” of amino acids: isoleucine, leucine, and valine.
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16. Figure 26-62 The biosynthesis of chorismate, the aromatic amino acid precursor.
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17. Figure 26-63 The biosynthesis of phenylalanine, tryptophan, and tyrosine from chorismate.
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18. Figure 26-64 A ribbon diagram of the bifunctional enzyme tryptophan synthase from S. typhimurium
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19. Figure 26-65 The biosynthesis of histidine.
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