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 nonessential amino acid
in order to have it for
use in the cells.
Some non-essential amino acid syntheses
are straightforward
• These
have
been
seen
elsewhere 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)