FCH 532 Lecture 27

Chapter 26: Essential amino acidsQuiz Wed: NIH ShiftQuiz Mon: Essential amino acidsExam 3: Next Wed.

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

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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

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glutamyl kinase

6. Acetylglutamate kinase

• N-acetyl--glutamyl phosphate dehydrogense

• N-acetylornithine--aminotransferase

• Acetylornithine deacetylase

• ornithine--aminotransferase

• Urea cycle to arginine

Arginine synthesis

Figure 26-58The conversion of glycolytic intermediate 3-

phosphoglycerate to serine.

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1. Conversion of 3-phosphoglycerate’s 2-OH group to a ketone

2. Transamination of 3-phosphohydroxypyruvate to 3-phosphoserine

3. Hydrolysis of phosphoserine to make Ser.

Serine is the precursor for Gly

• Ser can act in glycine synthesis in two ways:1. Direct conversion of serine to glycine by hydroxymethyl transferase in

reverse (also yields N5, N10-methylene-THF)2. 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.

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1. Methionine adenosyltransferase

2. Methyltransferase

3. Adenosylhomocysteinase

4. Methionine synthase (B12)

5. Cystathionine -synthase (PLP)

6. Cystathionine -synthase (PLP)

7 -ketoacid dehydrogenase

8. Propionyl-CoA carboxylase (biotin)

9. Methylmalonyl-CoA racemase

10. Methylmalonyl-CoA mutase

11. Glycine cleavage system or serine hydroxymethyltransferase

12. N5,N10-methylene-tetrahydrofolate reductase (coenzyme B12 and FAD)

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. (a) The

synthesis of cysteine from serine in plants and

microorganisms.

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Figure 26-59bCysteine biosynthesis. (b) The 8-electron reduction of sulfate to sulfide in E. coli.

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1. Sulfate activation by ATP sulfuylase and adeosine-5’-phosphosulfate (APS) kinase

2. Sulfate reduced to sulfite by 3’-phosphoadenosine-5’-phosphosulfate (PAPS) reductase

3. Sulfite to sulfide by sulfite reductase

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.

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biosynthesis of the “aspartate family” of amino acids: lysine,

methionine, and threonine.

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biosynthesis of the “pyruvate family” of

amino acids: isoleucine, leucine,

and valine.

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Figure 26-62 The biosynthesis of chorismate, the

aromatic amino acid precursor.

Figure 26-63The

biosynthesis of phenylalanine, tryptophan, and

tyrosine from chorismate.

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

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Figure 26-65The biosynthesis of

histidine.

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