ALANINE (abbreviated as ALA or A) is an α-amino acid that is used in
the biosynthesis of proteins . It contains an α-amino group (which is
in the protonated form, −NH3+, under biological conditions), an
α-carboxylic acid group (which is in the deprotonated form,
−COO−, under biological conditions), and a side chain methyl group
, making it a nonpolar , aliphatic amino acid. It is non-essential in
humans: because the body can synthesize it, it does not need to be
present in the diet. It is one of the 20 amino acids encoded by the
human genetic code , and is encoded by all codons starting with GC,
namely GCU, GCC, GCA, and GCG.
The L-isomer of alanine (left-handed ) is the one that is
incorporated into proteins. L-
Alanine is second only to leucine in
rate of occurrence, accounting for 7.8% of the primary structure in a
sample of 1,150 proteins . The right-handed form, D-
Alanine occurs in
polypeptides in some bacterial cell walls p. 131 and in some peptide
antibiotics , and occurs in the tissues of many crustaceans and
molluscs as an osmolyte .
* 1 History and etymology
* 2 Structure
* 3 Sources
* 3.1 Dietary sources
* 3.2 Biosynthesis
* 3.3 Chemical synthesis
* 3.4 Degradation
* 4 Physiological function
* 4.2 Link to diabetes
* 5 Chemical properties
* 5.1 Free radical stability
* 6 References
* 7 External links
HISTORY AND ETYMOLOGY
Alanine was first synthesized in 1850 by
Adolph Strecker . The
amino acid was named Alanin in German, in reference to aldehyde , with
the infix -an- for ease of pronunciation, the German ending -in used
in chemical compounds being analogous to English
Alanine is an aliphatic amino acid, because the side-chain connected
to the α-carbon atom is a methyl group (-CH3), making it the simplest
α-amino acid except for glycine . The methyl side-chain of alanine is
non-reactive and is therefore hardly ever directly involved in protein
Because alanine's side-chain cannot be phosphorylated, it is useful
in loss of function experiments with respect to phosphorylation . Some
techniques involve creating a library of genes, each of which has a
point mutation at a different position in the area of interest,
sometimes even every position in the whole gene: this is called
"scanning mutagenesis". The simplest method, and the first to have
been used, is so-called "alanine scanning", where every position in
turn is mutated to alanine.
Alanine is a nonessential amino acid , meaning it can be manufactured
by the human body, and does not need to be obtained through the diet.
Alanine is found in a wide variety of foods, but is particularly
concentrated in meats.
Alanine can be synthesized from pyruvate and branched chain amino
acids such as valine , leucine , and isoleucine .
Alanine is most commonly produced by reductive amination of pyruvate
, a two-step process. In the first step, α-ketoglutarate , ammonia
NADH are converted by glutamate dehydrogenase to glutamate , NAD+
and water. In the second step, the amino group of the newly-formed
glutamate is transferred to pyruvate by an aminotransferase enzyme,
regenerating the α-ketoglutarate, and converting the pyruvate to
alanine. The net result is that pyruvate and ammonia are converted to
alanine, consuming one reducing equivalent . p. 721 Because
transamination reactions are readily reversible and pyruvate is
present in all cells, alanine can be easily formed and thus has close
links to metabolic pathways such as glycolysis , gluconeogenesis , and
the citric acid cycle .
Racemic alanine can be prepared by the condensation of acetaldehyde
with ammonium chloride in the presence of sodium cyanide by the
Strecker reaction , or by the ammonolysis of 2-bromopropanoic acid :
Alanine is broken down by oxidative deamination , the inverse
reaction of the reductive amination reaction described above,
catalyzed by the same enzymes. The direction of the process is largely
controlled by the relative concentration of the substrates and
products of the reactions involved. p. 721
In mammals, alanine plays a key role in glucose–alanine cycle
between tissues and liver. In muscle and other tissues that degrade
amino acids for fuel, amino groups are collected in the form of
glutamate by transamination .
Glutamate can then transfer its amino
group to pyruvate , a product of muscle glycolysis , through the
action of alanine aminotransferase , forming alanine and
α-ketoglutarate . The alanine enters the bloodstream, and is
transported to the liver. The alanine aminotransferase reaction takes
place in reverse in the liver, where the regenerated pyruvate is used
in gluconeogenesis , forming glucose which returns to the muscles
through the circulation system.
Glutamate in the liver enters
mitochondria and is broken down by glutamate dehydrogenase into
α-ketoglutarate and ammonium , which in turn participates in the urea
cycle to form urea which is excreted through the kidneys.
The glucose–alanine cycle enables pyruvate and glutamate to be
removed from the muscle and safely transported to the liver, where
glucose is regenerated from pyruvate and then returned to muscle: this
moves the energetic burden of gluconeogenesis to the liver instead of
the muscle, and all available ATP in the muscle can be devoted to
muscle contraction. It is a catabolic pathway, and relies upon
protein breakdown in the muscle tissue. Whether and to what extent it
occurs in non-mammals is unclear.
LINK TO DIABETES
Alterations in the alanine cycle that increase the levels of serum
alanine aminotransferase (ALT) are linked to the development of type
Alanine (left) and (R)-alanine (right) in zwitterionic form
at neutral pH
FREE RADICAL STABILITY
The deamination of an alanine molecule produces a stable alkyl free
radical , CH3C•HCOO−.
Deamination can be induced in solid or
aqueous alanine by radiation.
This property of alanine is used in dosimetric measurements in
radiotherapy . When normal alanine is irradiated, the radiation causes
certain alanine molecules to become free radicals, and, as these
radicals are stable, the free radical content can later be measured by
electron paramagnetic resonance in order to find out how much
radiation the alanine was exposed to. This is considered to be a
biologically relevant measure of the amount of radiation damage that
living tissue would suffer under the same radiation exposure.
Radiotherapy treatment plans can be delivered in test mode to alanine
pellets, which can then be measured to check that the intended pattern
of radiation dose is correctly delivered by the treatment system.
* ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford,
Clarendon Press, 1959.
* ^ Doolittle, R. F. (1989), "Redundancies in protein sequences",
in Fasman, G. D., Prediction of
Protein Structures and the Principles
Protein Conformation, New York: Plenum, pp. 599–623, ISBN
* ^ A B C Mathews, Christopher K., (2000). Biochemistry. Van Holde,
K. E., Ahern, Kevin G. (3rd ed.). San Francisco, Calif.: Benjamin
Cummings. ISBN 0805330666 .
OCLC 42290721 .
* ^ Yoshimura, Tohru; Nishikawa, Toru; Homma, Hiroshi (2016-08-25).
D-Amino Acids: Physiology, Metabolism, and Application. Springer. ISBN
* ^ Strecker, A. (1850). "Ueber die künstliche Bildung der
Milchsäure und einen neuen, dem Glycocoll homologen" . Annalen der
Chemie und Pharmacie . 75 (1): 27–45. doi :10.1002/jlac.18500750103
. Cite uses deprecated parameter trans_title= (help ) Strecker names
alanine on p. 30.
* ^ Strecker, A. (1854). "Ueber einen neuen aus Aldehyd –
Ammoniak und Blausäure entstehenden Körper" and hydrocyanic acid].
Annalen der Chemie und Pharmacie . 91 (3): 349–351. doi
:10.1002/jlac.18540910309 . Cite uses deprecated parameter
trans_title= (help )
* ^ "Alanine".
* ^ "alanine". Oxford Dictionaries. Retrieved 2015-12-06.
* ^ Textbook of Biotechnology. McGraw-Hill Education (I). 2012.
ISBN 9780071070072 .
* ^ Park, Sheldon J.; Cochran, Jennifer R. (2009-09-25). Protein
Engineering and Design. CRC Press. ISBN 9781420076592 .
* ^ Kendall, E. C.; McKenzie, B. F. (1929). "dl-Alanine". Org.
Synth. 9: 4. ; Coll. Vol., 1, p. 21 .
* ^ A B Nelson, David L.; Cox, Michael M. (2005), Principles of
Biochemistry (4th ed.), New York: W. H. Freeman, pp. 684–85, ISBN
* ^ Fish Physiology: Nitrogen Excretion. Academic Press.
2001-09-07. p. 23. ISBN 9780080497518 .
* ^ Walsh, Patrick J.; Wright, Patricia A. (1995-08-31). Nitrogen
Metabolism and Excretion. CRC Press. ISBN 9780849384110 .
* ^ "Elevated
Aminotransferase Predicts New-Onset Type 2
Diabetes Independently of Classical Risk Factors, Metabolic Syndrome,
Protein in the West of Scotland Coronary Prevention
* ^ Zagórski, Z. P.; Sehested, K. (1998), "Transients and stable
radical from the deamination of α-alanine", J. Radioanal. Nucl.
Chem., 232 (1–2): 139–41, doi :10.1007/BF02383729 .
* ^ A B Pedro,, Andreo, (2017). Fundamentals of ionizing radiation
dosimetry. Burns, David T.,, Nahum, Alan E.,, Seuntjens, Jan P.,,
Attix, Frank H., (2nd ed.). Weinheim, Germany: WILEY-VCH. p. 547. ISBN
OCLC 990023546 .
Alanine MS spectrum