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.