FCH 532 Lecture 27
Chapter 26: Essential amino acids
Quiz Wed: NIH Shift
Quiz Mon: Essential amino acids
Exam 3: Next Wed.
Page 1030
Table 26-2
Essential and Nonessential Amino Acids in
Humans.
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 Nacetylglutamate 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
7. N-acetyl--glutamyl
phosphate
dehydrogense
8. N-acetylornithine-aminotransferase
Page 1036
9. Acetylornithine
deacetylase
10. ornithine-aminotransferase
11. Urea cycle to arginine
Page 1037
Figure 26-58 The conversion of
glycolytic intermediate 3phosphoglycerate to serine.
1. Conversion of 3phosphoglycerate’s 2-OH
group to a ketone
2. Transamination of 3phosphohydroxypyruvate
to 3-phosphoserine
3. Hydrolysis of
phosphoserine to make
Ser.
Serine is the precursor for Gly
•
1.
2.
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
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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1.
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.
Figure 26-59b
Cysteine
biosynthesis. (b) The 8electron 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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Figure 26-60 The
biosynthesis of the
“aspartate family” of
amino acids: lysine,
methionine, and
threonine.
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Figure 26-61 The
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 26-63
The
biosynthesis of
phenylalanine,
tryptophan, and
tyrosine from
chorismate.
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Figure 26-64 A ribbon diagram of the bifunctional
enzyme tryptophan synthase from S. typhimurium
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Figure 26-65 The
biosynthesis of
histidine.