FCH 532 Lecture 27
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Transcript of FCH 532 Lecture 27
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FCH 532 Lecture 27
Chapter 26: Essential amino acidsQuiz Wed: NIH ShiftQuiz Mon: Essential amino acidsExam 3: Next Wed.
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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
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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.
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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
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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)
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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.
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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
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Biosynthesis of essential amino acids
• Pathways only present in microorganisms and plants.• Derived from metabolic precursors.• Usually involve more steps than nonessential amino acids.
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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.
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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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