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AMINO
ACID METABOLISM: BIOSYNTHESIS CATABOLISM
OF THE TWENTY STANDARD AMINO ACIDS
What's
this?
One of my favorite
things I've discovered over the last few years
has been the complexity and mysteriousness of
the methods by which organisms synthesise amino
acids, the constituents of the 'working parts'
for every organism on the planet. At first, in
their isolated form, the pathways appear tortuous
and disordered; but once assimilated, a beuatiful
and all too apparent order begins to make itself
felt. While I feel that, apart from in these purple
and misplaced tones, this sense is impossible
to communicate without studying the pathways yourself,
I hoped I could emphasize the beauty, as well
as the complexity, by constructing a clear (and
vast) poster showing all of the biosynthetic and
catabolic pathways for all the standard amino
acids. The diagram contains the structures of
all the intermediates, enzyme names, as well as
cofactors and energy requirements. Each amino
acid is summarised as being essential or non-essential
to humans, on its synthetic meterials and cost,
catabolic products and ATP yield on complete catabolism,
and any other special requirements. It may be
big, but if you're into biochemistry and have
an appreciation of beautiful things, take a look
at my poster. The poster is in PDF (adobe acrobat)
format, which makes it less than 250K download;
so what have you got to lose? Note that to view
the diagram properly, zoom in almost to the maximum
extent allowed.
What's
the (hopeful) purpous of the diagram?
The biosynthesis and degradation
of the twenty standard amino acids represent the
complexity and ingenuity of metabolism at its
most astounding. The carbons skeletons of all
of these disparate and diverse compounds are derived,
universally throughout life on this planet, from
glycolytic intermediates, metabolites of the Krebs
cycle and the Pentose phosphate pathway, and in
the case of histidine from nucleotide (purine)
metabolism. Many amino acids that are superficially
unrelated have similar sources: aspartate, asparagine,
lysine, threonine and methionine all have their
origin in the Krebs cycle metabolite oxaloacetate
for example. And yet one immediate and striking
factor becomes apparent once the detail and complexity
of these pathways is assimilated: the similarity
apparently unconnected pathways have to each other,
and to the other pathways of carbohydrate or lipid
metabolism, varient in such a subtle and continuous
manner to supply a continuous range of organic
functional groups with which to array the amino
acids used in protein synthesis. Thus, the two
acidic amino acids glutamate and aspartate are
both derived from simple transaminations of two
anaologous (even homologous) metabolites of the
Krebs cycle, alpha-ketoglutarate and oxaloacetate.
Amidisation gives two polar amino acids, glutamine
and asparagine, and further derivatives are produced
by NADPH dependent reduction of the terminal carboxyl
group to a aldehyde, leading to cyclc schiff bases,
and ultimately metabolised to lysine and proline
respectively. Pleasing, and diagramatically prophitable,
as this symettry is, it is nothing as compared
to the interlocking and conintually shifting motifes
of â-oxidation and claisen ester condensation,
Krebs cycle reactions and continually recurring
reaction such as the decarboxylation of á-keto
acids to yield acyl-CoA, and the almost mathematically
propitious importance of odd and even number carbon
chains. Pathways such as the formation of the
brached chain hydrophobic amino acids (leucine,
isoleucine and valine) are a direct example of
this: formation of the principles, isoleucine
and valine, occurs through the mixed claisen/aldol
condensation of acetyl-CoA, as directly derived
from pyruvate, with either pyruvate itself or
its four carbon homologue, á-ketobutyrate;
itself derived from threonine in a reaction primarily
attributed to its fellow hydroxy-bearing amino
acid in serine dehydratase; in direct analogy
with the first reaction of the Krebs cycle. The
adducts are then reduced and dehydrated, immediately
reminiscent of the stages following ester condensation
in fatty-acid biosynthesis. This combination is
repeated upon itself in the conversion of the
metabolites to leucine; a futher condensation
with acetyl-CoA ; but in contrast, the adduct
is isomerised and oxidatavley decarboxylated in
a manner very similar to the continuing steps
in the Krebs cycle. All the ingenuity of the basic
metabolic pathways of carbohydrates and fatty
acids has been harnessed to yield a spectrum of
protein components; common motifs are mixed and
recombined, defined chemistry is applied to novel
substartes, and echoes of each pathway reverberate
throughout the whole system. Amino acid biosynthesis
is not only a symbol for the complexity and elegance
of metabolism; it also represents the ever recombining
genome, the functional exon as the unit of recombination
in eukaryotes and the subtlety of nature in expanding
a handful of effective chemical mechanisms throught
the entirely logical, but profoundly mysterious
methods of natural selection. Catabolism of each
amino acid is at least as fascinating, and offers
some insight into the metabolic “value”
of each amino acid: the amount of ATP or reducing
power that can be obtained through complete oxidation
of its carbon chain to CO2 and water. In addition,
since mammals ingest every standard amino acid
in the form of protein, but rarely use all of
this for protein synthesis, catabolic pathways
for every one must exist throughout the whole
animal kingdom. Again, the auspices of the enzymes
derived from standard metabolism are more than
in evidence. Amino acids are catabolised either
to glucogenic (á-ketoglutarate, oxaloacetate,
fumerate, succinyl-CoA, or pyruvate) or ketogenic
(acetyl-CoA, acetoacetate) products, much depending
on the oxdisation state of the amino acid: phenylalanine,
for instance, is both; the highly reduced phenyl
group becoming (after consideable aerobic oxidation)
HMG-CoA, and the peptide moeity becoming fumerate.
The metabolism of the amino acids is in itself
another basis for more complex or specialised
reactions, utilising the scemata of these pathways
in the same way that the reactions characterised
below employ the other metabolic pathways. Common
enzyme structure, mechanism and themes can be
detected throughout pathways in disparate organisms,
in different kingdoms, in entirely different environments.
The universality of the basic reactions (as well
as the informative exceptions) is yet another
example of the deep rooted, and all pervading,
unity of the life on this planet.
View
the poster (Adobe PDF format, 192 Kb)
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