SELENOCYSTEINE, PYRROLYSINE,

NEW DISCOVERY OF AMINO ACIDS

Created by :
Agustinus C B Kantale
Muhammad Resa
*
 Introduction

When the triplet nature of the genetic code was discovered, it

was thought that there are only 20 amino acids determined by
four nucleotides of the universal genetic code and that each of
the 64 triplet codon has only one sense.
Selenium initialy believed to be toxic(more than sulfur).
1954: 1st report of Se requirement for function of bacterial
formate dehydrogenase.
1959: 1st paper addressing Selenocystine.
1972: 1st biochemical studies on role of Se at enzyme level.
1986: key study implicating UGA as codon for Sec.
 Introduction

21st proteogenic amino acid

Discoverd by biochemist THERESA STADTMAN at National
Health of Institute.
Exist naturally in all kingdoms of life as a building block of
selenoproteins
Present in several enzymes, eg. Glutathione peroxidase,
thioredoxine reductase, formate dehydrogenases, glycine
reductase, selenophosphate synthase1 and some
hydrogenases.
STRUCTURE
 PROPERTIES

3 letter code Sec

1 letter code U
Codon UGA
IUPAC Name 3-selanyl-2-aminopropanoic acid
Other name Selenium cystine, L-selenocystine
Molecular formula C3H7NO2Se
Molar mass 168.05 g/mol
Pka 5.47
pI 5.47
Melting point 143-146°C
polor acidic
Water Solubility 5 mg/L
 Unique feature of Sec

 Other unique features of Sec, not shared by any

of the other 20 common amino acids, derive from
the Atomic weight and Chemical properties of
selenium and the particular occurance and
properties of its stable and radioactive isotopes.
CYSTINE V/S SELENOCYSTINE

Sec contain selenium in the place

of sulphur of Cys.
Sec has both lower pka (5.47) &
lower reduction potential than Cys.
Sec is strong nucleophilic than
Cys.
“These prorerties make it very
suitable in protein, involved in
antioxidant activity”.
 BIOSYNTHESIS
The biosynthesis of this amino acid occurs on the tRNA which needs
to be first acylated with serine and then is subsequently
transformed into selenocysteine by an enzyme synthase that
further utilizes selenophosphate in the form of selenium donor and
the cofactor pyridoxal phosphate.
 UGA CODON
● UGA : termination codon and Sec codon.
● Discovered by Bock in 1986 in bacterial formate dehydrogenase
(FDH).
● In vivo studies confirmed that Sec tRNA [Ser] Sec recognize the
UGA codon in both bacteria and eukaryotes.
 IN PROKARYOTES
●

In prokayotes, an operon consisting of four genes known as the Sel operon is also
necessary for the incorporation of selenocysteine into proteins.
●
Genes of the sel operon
sel A- converts serine to dehydroalanine
●

sel B- codes for an EF-Tu like translation

●

●
factor sel C- codes for the specific
selenocysteine tRNA sel D- “activates”
HSe-
 IN EUKARYOTES
●
Eukayotes do not contain Sel operon.
● Sec Insertion Sequence (SECIS) element play important role in translation.
● Other factors are:
●
SBP2- SECIS binding protein.
●
EEFsec- traslation factor,help in binding to ribosome.
 SOURCES

Selenocysteine is found in proteins and in variety of foods

of either animal origin or plant origin.
Animal origin: Selenocysteine animal sources are meat,
poultry, chicken, egg, cheese fish, seafood and turkey.
Plant origin: Selenocysteine of plant origin contains wheat,
oats, corn, rice, nuts especially of Brazil nuts, soybeans.
Selenocysteine is available in the food in the form of
selenomethionine.
In some foodstuff it occurs in the form of selenate.
 FUNCTION
S

The important functions of selenocysteine in proteins are its

antioxidant activity. This is due to its lower pKa and higher
reduction potential.
It is also used in the preparation of variety of vitamins and
lots of other supplements.
It is also fortified with livestock feeds.
Our body utilizes selenocysteine to form selenium, which is
believe to play important role in preventing mercury toxicity
as well as enhance liver functions.
IMPORTANCE OF SEC FOR HEALTH:
Biological role of selenium

In 1930 selenium was found respontibal for sever human

disease (US).
Cardiomiopathy was recorded in children and young woman
(China,1930),called Keshan disease.
Deficient with selenium have lean body mass, prone to
premature aging or to heart disease.
Selinium has cancer prevention effect (mediobiological and
clinical report 1970-1990).
IMPORTANCE OF SEC FOR HEALTH:
Biological role of selenium

Regulation of thyroyid hormone.

It has been discovered that HIV-1 encodes a functional
selenoprotein. Patients with HIV have been shown to have a
lower than average blood plasma selenium level.
Deficiancy of this element cause viral infection (transform
avirulent strain into a virulent one).
 Pyrrolysine
The 22nd amino acid
 Properties
3- letter code Pyl
1 letter code O

Genetic codon UAG

Molecular formula C12H21N3O3

Molecular weight 255.313 g/mol
Boiling point 546.9 ± 50 °C at
760mmHg

Polar Weak basic

 Biosynthesis

●
Pyrrolysine is synthesized in vivo by joining two molecules of
L-lysine.
●
One molecule of lysine is first converted to (3R)-3-Methyl-D-
ornithine, which is then ligated to a second lysine.
●
An NH2 group is eliminated, followed by cyclization and
dehydration step to yield L-pyrrolysine
 Fig. 2: Proposed route of pyrrolysine
biosynthesis. In addition the names of the
enzymes are mentioned which catalyze
the reaction steps (adapted from (1),
originally proposed by (2)).

https://johanneswilbertz.com/2011/11/22/pyrrolysine-the-22nd-amino-acid/
 Functions
Pyrrolysine reactivity with nucleophiles suggests the ability to
participate in corrinoid dependent methylamine methyl-
transferase reactions by interacting with either the
methaloamine substrate or product.
Used by some methanogenic archaea and one known
bacterium (Methanosarcina barkeri), in enzymes that are
part of their methane-producing metabolism.
Methanobrevibacter smithii is a prominent methanogen
in the human gut, where it helps digest polysaccharides,
or complex sugars.
 REFERENCES
http://www.dailyhealthmagazine.com/selenocysteine/
http://www.researchgate.net/topic/selenocysteine
●

http://www.rcsb.org/pdb/101/motm.do?momID=104
●

https://etd.ohiolink.edu/ap/10?0::NO:10:P10_ACCESSION_NUM:osu131853
●
3705

●
http://www.chemspider.com/Chemical-Structure.4574156.html
https://johanneswilbertz.com/2011/11/22/pyrrolysine-the-22nd-amino-acid/
http://www.nutrientsreview.com/proteins/amino-acids/selenocysteine.html
https://www.sciencedaily.com/releases/2011/11/111118133052.htm
Gayathri Srinivasan et al., 2002, Pyrrolysine Encoded by UAG in Archaea:
Charging of a UAG-Decoding Specialized tRNA
Michael Rother et al, 2010,Selenocysteine, Pyrrolysine, and the Unique
Energy Metabolism ofMethanogenic Archaea