Beruflich Dokumente
Kultur Dokumente
Marie-Véronique CLEMENT
Associate Professor
Yong Loo Lin School of Medicine
NUS Graduate School for Integrative Science and Engineering
Department of Biochemistry
National University of Singapore
8 Medical Drive, MD 7 #03-15
Singapore 117597
Tel: (65) 68747985
Fax: (65) 67791453
bchmvc@nus.edu.sg
E-mail:
Amino Acids
9 essential
20 Amino Acids: 11 non essential
General formula At physiological pH
of an Amino Acid
COO/NH3+
All amino acids are in the Lconfiguration
•Unsubstituted
• Heterocyclic
• Aromatic
• Thioether
• hydroxy
All amino acids have a specific side chain • Mercapto
• Carboxiamide
• Monoamino, dicarboxylic
• Diamino, monocarboxylic
Amino acid side chain can be
polar/hydrophilic
Non polar/hydrophobic
Acid/base properties of amino acids:
Acid/base properties of side chains
acid base
Carboxyl group
Imidazole group
webhost.bridgew.edu/fgorga/proteins/zwitterions.htm
And
Lippincott’s
Titration
curve of
Alanine
RH3N+ RNH2 + H+
RCOO + H
+
RCOOH
All amino acids found in proteins are Lconfiguration.
DAmino acid are found in plant, antibiotics and bacterial walls
D amino acid are efficiently metabolized by the liver by the D
Amino acid oxidase. However, DAmino acid are reaminated to
Lisomers during amino acid metabolism.
The four main families of small organic molecules
in cells
From amino acids Formation of a protein Amino acid
to protein:
RNAs: blue
Ribosome: green
Protein: red
codon The genetic
code
Amino acid
One or more codon
correspond to 1
standard amino acid:
The dogma till 1983:
20 amino acids are enough to produce all the proteins in
our body
20
not enough!
When stop means go:
Stop codon
1983
Selenocysteine (21)
Pyrrolysine (22)
2002
There are two ways in which the stop codon UAG could be redefined to specify the 22nd
amino acid, pyrrolysine. In the first (top), special signals in mRNAs tag a subset of stop
codons that are to have their meaning redefined. In the second (bottom), a codon is
redefined regardless of the mRNA involved.
Selenocystein
Selenocysteine is an amino acid that is present in several
enzymes
(glutathione peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin
reductases, formate dehydrogenases, glycine reductases and some
hydrogenases).
Selenocysteine has a structure similar to cysteine, but with an atom of selenium taking the
place of the usual sulfur.
Selenium is a vital nutrient in animals and humans.
Proteins that contains one or more selenocysteine residues are called selenoproteins.
About 25 different selenocysteine-containing selenoproteins have so far been
observed in human cells and tissues.
Since lack of selenium deprives the cell's ability to synthesize selenoproteins, many
health effects of low selenium intake are believed to be caused by the lack of one or
more specific selenoproteins.
On the other side, too much selenium in the diet causes toxic effects and leads to
selenium poisoning.
The threshold between essential and toxic concentrations of this element is rather
narrow (the factor is in the range of 10-100).
Pyrrolysine
Pyrrolysine is an amino acid used by some
methanogenic (organisms that produce
methane) archaea in enzymes that are part
of their methane-producing metabolism.
Pyrrolysine is a lysine derivative encoded by the UAG codon in methylamine methyltransferase genes of
Methanosarcina barkeri. Near a methyltransferase gene cluster is the pylT gene, which encodes an unusual transfer RNA (tRNA)
with a CUA anticodon. The adjacent pylS gene encodes a class II aminoacyl-tRNA synthetase that charges the pylT-derived tRNA
with lysine but is not closely related to known lysyl-tRNA synthetases. Homologs of pylS and pylT are found in a Gram-positive
bacterium. Charging a tRNACUA with lysine is a likely first step in translating UAG amber codons as pyrrolysine in certain
methanogens. Our results indicate that pyrrolysine is the 22nd genetically encoded natural amino acid.
Phosphoserine in the survival kinase Akt?
Neurotransmitter, Dopamine?
The non standard amino acids
Non Standard amino acids
Produce from modifications of standard amino acids
Modified after it is incorporated Do not incorporate into a protein
into the protein. Biologically active amino acids:
• Hydroxylation • GABA (2 amino isobutiric acid)
• Acetylation • Dopamine (neurotransmitter)
• Phosphorylation • Taurine (essential for development)
• Crosslinking of cystein • Histamine (neuritransmitter)
• Thyroxine (thyroid hormone, increase the basal
metabolic rate, affect protein synthesis and increase the body's
sensitivity to catecholamines (such as adrenaline).
• Epinephrine (or adrenaline, is a neurotransmitter
and an hormone)
Post-translational modifications of amino acids:
Phosphorylation of serine
/threonine or tyrosine is used in
cell signaling
Crosslinking of two cysteines to form a new amino acid, called cystine
Biologically active amino acids:
Dopamine:
GABA: Synthesized from tyrosine
gamma Amino butyric acid
In the brain, dopamine functions as a
Synthesised from glutamate neurotransmitter, activating dopamine
receptors. Dopamine is also a
GABA acts at inhibitory synapses in neurohormone released by the
the brain. GABA acts by binding to hypothalamus. Its main function as a
specific receptors in the plasma hormone is to inhibit the release of
membrane of both pre- and prolactin from the anterior lobe of the
postsynaptic neurons. pituitary.
Neurotransmetter
Taurine :
2-aminoethanesulfonic acid,
formed by the decarboxylation of cysteine
Non standard amino acids
• Modified after it is incorporated into the
protein.
• Do not incorporate into a protein
Biologically active amino acids:
?
Amino acids protein
How to make a protein?
Amino acids join together to form proteins:
Variable
side chains
Trans is the
Favorite conformation
Except!
Cis
A peptide: PheSerGluLys (FSEK)
Nterminus
terminates
by an amino group
Peptide bond
Amino acid
Cterminus
terminates by a
carboxyl group
Amino Acid Sequences Have Direction:.
Backbone
Variable side chains
What is the difference between a
peptide and a protein?
Peptide < 50 amino acids
Protein > 50 amino acids
A protein (from the Greek protas meaning "of primary importance")
Molecular weight Isoelectric point
The molecular weight of a protein:
Molecular weight of protein is expressed in Dalton
The mean molecular weight of an amino acid residue is about 110, and so the
molecular weights of most proteins are between 5500 and 220,000.
Electrophoresis of Hepatic
plasma protein cirrhosis
and diseases
Inflamation
cause by
infection
Nephrotic
syndrome
Hypoγ globulinemia
immunosupressive disease