General features
R = -(CH2)2COO-
at cytoplasmic pH (pH~7)
pKa (terminal carboxyl group)= 4.25
Physiological roles
In
prokaryotes, an important function is to donate its alpha-amino group to other
amino acids that are being synthesized:
Each transaminase enzyme is specific for the amino acid that
will be aminated (or deaminated).
Details of the mechanism can be found here: http://www.bmb.leeds.ac.uk/illingworth/bioc1010/index.htm
Another
function of L-glutamate is to maintain regular L-glutamine levels while
assimilating nitrogen in one of two pathways (to be discussed below and in the
next post). Also, it can be fermented in various pathways under anaerobic
conditions (X).
A
structural function is that its enantiomer, D-glutamate is typically a member
of the tetrapeptide bridge in peptidoglycan linkages:
L-glutamate is first added to L-alanine, then glutamate
racemase (murI) will convert it to the D enantiomer.
Another
notable structural function of D-glutamate is in the poly-D-glutamyl capsule of
Bacillus anthracis, the capsule being one of its main virulence factors
(avoidance of phagocytosis). More on this requirement for B. anthracis pathogenicity can be found: http://www.nature.com/emboj/journal/v24/n1/full/7600495a.html#B25
Synthesis
Like many
of the amino acids, L-glutamate corresponds to a ‘parent’ metabolite of the TCA
cycle, α-ketoglutarate, whose supply can be increased or decreased depending on
the relative need for glutamate and its downstream products. When α-ketoglutarate
derivatives are highly demanded, they will deplete its supply and are thus
cataplerotic, taking TCA carbons from the cycle. When α-ketoglutarate
derivatives are used to increase its concentration because some other portion
of the TCA cycle requires concentrations of its intermediates (say, an increase
demand for fumarate for tyrosine synthesis), the conversion of glutamate to
α-ketoglutarate would be anaplerotic, because it would be adding carbons to the
TCA cycle.
L-glutamate can be regenerated by two significant enzmes,
either from existing pools of glutamine + α-ketoglutarate (glutamate synthase,
GS) or via NH4+ + α-ketoglutarate (glutamate dehydrogenase, GOGAT. In the
synthesis of glutamate, this enzyme seems to be named backwards).
The pathway that uses glutamate synthase (GOGAT) is often
coupled with glutamine synthase (GS) for the constant recycling of
glutamate/glutamine. The second pathway that uses glutamate dehydrogenase (GDH)
is not used as often because the the enzyme itself favors an equilibrium more
toward the ammonium, α-ketoglutarate products due to its high Km for
NH3 (meaning it needs a higher [NH3] to bind this
substrate). Use of this enzyme under normal [NH3] would then lead to an excess
of un-assimilated/free ammonia within the cell which is toxic. Also of interest
is the fact that GDH does not use an ATP for the catalysis of its reaction. So
generally speaking, under high [NH3] and low energy levels the bacterial cell
will use glutamate dehydrogenase. The glutamate/glutamine pair, which differ by
an amino group, is used for nitrogen assimilation (as will be described in the
next post). Given this difference, it is convenient for the cell to
continuously cycle them to maintain a constant level of intracellular ammonia.
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