Nitrogen fixation 310

[15] Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl Substituents Dmitry V. Yandulov,
Richard R. Schrock, Arnold L. Rheingold, Christopher Ceccarelli, and William M. Davis Inorg. Chem.; 2003; 42(3) pp 796–813; (Article)
doi:10.1021/ic020505l
[16] Catalytic Reduction of Dinitrogen to Ammonia at a Single Molybdenum Center Dmitry V. Yandulov and Richard R. Schrock Science 4 July
2003: Vol. 301. no. 5629, pp. 76–78 doi:10.1126/science.1085326
[17] The catalyst is based on molybdenum(V) chloride and tris(2-aminoethyl)amine substituted with three very bulky hexa-isopropylterphenyl
(HIPT) groups. Nitrogen adds end-on to the molybdenum atom, and the bulky HIPT substituents prevent the formation of the stable and
nonreactive Mo-N=N-Mo dimer, and the nitrogen is reduced in an isolated pocket. The proton donor is a pyridinium cation, which is
accompanied by a tetraborate counter ion. The reducing agent is decamethylchromocene. All ammonia formed is collected as the HCl salt by
trapping the distillate with a HCl solution
[18] Note also that, although the dinitrogen complex is shown in brackets, this species can be isolated and characterized. Here the brackets do not
indicate that the intermediate is not observed.
[19] A molybdenum complex bearing PNP-type pincer ligands leads to the catalytic reduction of dinitrogen into ammonia Kazuya Arashiba,
Yoshihiro Miyake Yoshiaki Nishibayashi Nature Chemistry Volume: 3, Pages: 120–125 Year published:(2011 doi:10.1038/nchem.906

External links
• NITROGEN FIXATION (http://lupins-bk.blogspot.com/2006/07/nitrogen-fixation.html)

Amino acid synthesis

For the non-biological synthesis of amino acids see: Strecker amino acid synthesis
Amino acid synthesis is the set of biochemical processes (metabolic pathways) by which the various amino acids
are produced from other compounds. The substrates for these processes are various compounds in the organism's diet
or growth media. Not all organisms are able to synthesise all amino acids. For example, humans are able to
synthesise only 12 of the 20 standard amino acids.
A fundamental problem for biological systems is to obtain nitrogen in an easily usable form. This problem is solved
by certain microorganisms capable of reducing the inert N≡N molecule (nitrogen gas) to two molecules of ammonia
in one of the most remarkable reactions in biochemistry. Ammonia is the source of nitrogen for all the amino acids.
The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.
In amino acid production, one encounters an important problem in biosynthesis, namely stereochemical control.
Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high
fidelity. In each of the 19 pathways for the generation of chiral amino acids, the stereochemistry at the α-carbon
atom is established by a transamination reaction that involves pyridoxal phosphate. Almost all the transaminases that
catalyze these reactions descend from a common ancestor, illustrating once again that effective solutions to
biochemical problems are retained throughout evolution.
Biosynthetic pathways are often highly regulated such that building-blocks are synthesized only when supplies are
low. Very often, a high concentration of the final product of a pathway inhibits the activity of enzymes that function
early in the pathway. Often present are allosteric enzymes capable of sensing and responding to concentrations of
regulatory species. These enzymes are similar in functional properties to aspartate transcarbamoylase and its
regulators. Feedback and allosteric mechanisms ensure that all twenty amino acids are maintained in sufficient
amounts for protein synthesis and other processes.
Amino acid synthesis 311

Amino acid synthesis

Amino acids are synthesized from α-ketoacids, and later transaminated from another aminoacid, usually Glutamate.
The enzyme involved in this reaction is an aminotransferase.
α-ketoacid + glutamate ⇄ amino acid + α-ketoglutarate
Glutamate itself is formed by amination of α-ketoglutarate:
α-ketoglutarate + NH ⇄ glutamate

Nitrogen fixation: Microorganisms use ATP and a powerful reductant to

reduce atmospheric nitrogen to ammonia
Microorganisms use ATP and reduced ferredoxin, a powerful reductant, to reduce N2 to NH3. An iron-molybdenum
cluster in nitrogenase deftly catalyzes the fixation of N2, a very inert molecule. Higher organisms consume the fixed
nitrogen to synthesize amino acids, nucleotides, and other nitrogen-containing biomolecules. The major points of
entry of NH4+ into metabolism are glutamine or glutamate.

Amino acids are made from intermediates of the citric acid cycle and other
major pathways
Of the basic set of 20 amino acids (not counting selenocysteine), there are 8 that human beings cannot synthesize. In
addition, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered
conditionally essential, meaning they are not normally required in the diet, but must be supplied exogenously to
specific populations that do not synthesize it in adequate amounts.[1] [2] For example, enough arginine is synthesized
by the urea cycle to meet the needs of an adult but perhaps not those of a growing child. Amino acids that must be
obtained from the diet are called essential amino acids. Nonessential amino acids are produced in the body. The
pathways for the synthesis of nonessential amino acids are quite simple. Glutamate dehydrogenase catalyzes the
reductive amination of α-ketoglutarate to glutamate. A transamination reaction takes place in the synthesis of most
amino acids. At this step, the chirality of the amino acid is established. Alanine and aspartate are synthesized by the
transamination of pyruvate and oxaloacetate, respectively. Glutamine is synthesized from NH4+ and glutamate, and
asparagine is synthesized similarly. Proline and arginine are derived from glutamate. Serine, formed from
3-phosphoglycerate, is the precursor of glycine and cysteine. Tyrosine is synthesized by the hydroxylation of
phenylalanine, an essential amino acid. The pathways for the biosynthesis of essential amino acids are much more
complex than those for the nonessential ones.
Tetrahydrofolate, a carrier of activated one-carbon units, plays an important role in the metabolism of amino acids
and nucleotides. This coenzyme carries one-carbon units at three oxidation states, which are interconvertible: most
reduced—methyl; intermediate—methylene; and most oxidized—formyl, formimino, and methenyl. The major
donor of activated methyl groups is S-adenosylmethionine, which is synthesized by the transfer of an adenosyl group
from ATP to the sulfur atom of methionine. S-Adenosylhomocysteine is formed when the activated methyl group is
transferred to an acceptor. It is hydrolyzed to adenosine and homocysteine, the latter of which is then methylated to
methionine to complete the activated methyl cycle.
Cortisol inhibits protein synthesis.[3]
Amino acid synthesis 312

Amino acid biosynthesis is regulated by feedback inhibition

Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition, in which the committed step
is allosterically inhibited by the final product. Branched pathways require extensive interaction among the branches
that includes both negative and positive regulation. The regulation of glutamine synthetase from E. coli is a striking
demonstration of cumulative feedback inhibition and of control by a cascade of reversible covalent modifications.

Amino acids are precursors of many biomolecules

Amino acids are precursors of a variety of biomolecules. Glutathione (γ-Glu-Cys-Gly) serves as a sulfhydryl buffer
and detoxifying agent. Glutathione peroxidase, a selenoenzyme, catalyzes the reduction of hydrogen peroxide and
organic peroxides by glutathione. Nitric oxide, a short-lived messenger, is formed from arginine. Porphyrins are
synthesized from glycine and succinyl CoA, which condense to give δ-aminolevulinate. Two molecules of this
intermediate become linked to form porphobilinogen. Four molecules of porphobilinogen combine to form a linear
tetrapyrrole, which cyclizes to uroporphyrinogen III. Oxidation and side-chain modifications lead to the synthesis of
protoporphyrin IX, which acquires an iron atom to form heme. [4]

References
[1] Fürst P, Stehle P (1 June 2004). "What are the essential elements needed for the determination of amino acid requirements in humans?" (http:/
/ jn. nutrition. org/ cgi/ content/ full/ 134/ 6/ 1558S). J. Nutr. 134 (6 Suppl): 1558S–1565S. PMID 15173430. .
[2] Reeds PJ (1 July 2000). "Dispensable and indispensable amino acids for humans" (http:/ / jn. nutrition. org/ cgi/ content/ full/ 130/ 7/ 1835S).
J. Nutr. 130 (7): 1835S–40S. PMID 10867060. .
[3] Manchester, K.L., “Sites of Hormonal Regulation of Protein Metabolism. p. 229”, Mammalian Protein [Munro, H.N., Ed.]. Academic Press,
New York. On p273.
[4] Biochemistry. Berg, Jeremy M.; Tymoczko, John L.; and Stryer, Lubert. New York: W. H. Freeman and Co. ; c2002

External links
• NCBI Bookshelf Free Textbook Access (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.TOC&
depth=2)