Amino acid biosynthesis

Chemistry 256

Why biosynthesis?

• So that every amino acid is not an essential one. In other words, humans do not have to consume a non-essential amino acid in order to have it for use in the cells.

Some non-essential amino acid syntheses are straightforward

• These have been seen else-where in the text.

Others less so...

Especially the aromatic ones!

A study in regulation: Glutamine synthetase

• D6 symmetry; mammalian glutamine synthetase is controlled by α-ketoglutarate to prevent ammonia accumulation.

Bacterial glutamine synthetase regulation• Much more complex; requires adenylylation, which is

the addition of an AMP to key tyrosine residues.• The enzyme adenylyltransferase is activated by

uridylylation, the addition of a UMP, a reaction catalyzed by uridylyltransferase.

• So, if there is high [α-ketoglutarate], this triggers uridylylation of adenylyltransferase, which activates it to adenylylate glutamine synthetase, which activates that to produce more glutamine.

• Not a digital system: different levels of uridylylation and adenylylation lead to different rates.

Woolfolk C. A., Stadtman E. R. , “Cumulative feedback inhibition in the multiple end-product regulation of glutamine synthetase activity in Escherichia coli”, Biochem. Biophys. Res. Commun. (1964).

Some amino acid syntheses are complex

• Glutamate leads to proline, ornithine, arginine (several steps)

• 3-phosphoglycerate (3PG) leads to serine, cysteine, glycine (several steps)

• Plants and microorganisms synthesize aspartate into lysine, methionine and threonine; pyruvate into leucine, isoleucine and valine; and so forth.

• The synthesis of histidine in plants is similar to the synthesis of nucleotides.

Westley, J., and Ceithaml, J., “Synthesis of Histidine in Escherichia Coli”, Arch. Biochem. And Biophys. (1955)

Heme is synthesized from glycine and succinyl-CoA

• Shemin, D., London, I.M., Rittenberg, D., “The in vitro synthesis of heme from glycine by nucleated red blood cells”, J Biol Chem (1948)

Heme is degraded and excreted

A variety of neurotransmitters and hormones are synthesized from amino acids

Nitrogen fixation by some bacteria (diazotrophs) requires nitrogenase

Yes, molybdenum is a nutrient!(for these bacteria, anyway)