Amino Acid biosynthesis Amino acids are derived from intermediates in glycolysis, citric acid cycle, and PPP pathway Ten of the amino acids have relatively.
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Amino Acid biosynthesis
• Amino acids are derived from intermediates in glycolysis, citric acid cycle, and PPP pathway
• Ten of the amino acids have relatively simple pathways compared to say aromatic amino acids
• Although many organisms can synthesize all 20, mammals can synthesize only about ½. Those they can synthesize are called non-essential amino acids. (You do not need to distinguish between essential and non-essential)
Grouping amino acids by biosynthetic routes
-KG is a source of four amino acids
• Glutamate and glutamine synthesis were described last lecture
• Proline is generated by cyclization of glutamate
• Arginine is made from glutamate and is an intermediate of the urea cycle (to be covered soon)
Proline can also be synthesized from arginine
3-phosphoglycerate is a precursor for serine, glycine and cysteine
• Highly conserved pathway
• Cysteine requires a sulfur
Sources of sulfur
• Plants and bacteria fix sulfates from environment and reduce it to sulfide which is used to generate cysteine from serine
• Animals derive their sulfur from the essential amino acid methionine (methionine catabolism in Chap. 18; methionine is broken down to homocysteine)
• PLP is pyridoxal
phosphate, a cofactor
in glycogen
phosphorylase
and aminotransferases
OAA is a precursor for potentially six amino acids
• Aspartate is generated by the transamination of OAA (glutamate donor)
• Asparagine is synthesized by amidation of aspartate, with glutamine donating ammonia
• Aspartate also gives rise to methionine, threonine, and lysine in pathways that can also utilize pyruvate or other amino acids (lots of interconnectivity)
Aspartate semialdehyde is a branch point
Lysine biosynthesis begins with formation of dihydropicolinate through addition of pyruvate
Following reduction, Succinyl-CoA is needed for lysine generation
A PLP-dependent aminotransferase adds an amine group
Ultimately, a PLP-dependent enzyme generates lysine
Meanwhile, back at the first branch point, a reduction can lead to another branch point
• Homoserine is a common precursor in methionine and threonine synthesis
Succinyl-CoA is involved in methionine biosynthesis
Methionine shares common intermediates with cysteine
Threonine is a two-step process from homoserine
Threonine is a precursor for isoleucine biosynthesis
Valine and isoleucine biosynthesis share four enzymes
Reduction follows addition of the aceto- group
Then a condensation reaction and transamination
An intermediate in valine synthesis, -keto-isovalerate branches into leucine biosynthesis
Subsequent oxidation and transamination result in leucine
Aromatic amino acid biosynthesis
• Begins with PEP and erythrose-4-phosphate in a pathway that ends with chorismate
• Chorismate serves as a branch point for pathways one leading to tryptophan, and the other leading to phenylalanine and tyrosine.
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