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.