Aminoacids Flashcards
Proteins. 3 points
.Proteins are of paramount importance for biological systems
.All the major structural and functional aspects of body are carried out by protein molecules
.All proteins are polymers of amino acids linked by peptide bonds
Total aa present in nature
- Only 20 of them are seen in human body
First aa to be discovered
Asparagine
First aa to be isolated
Leucine
20th aa
Threonine
21st aa
Selenocysteine
Exception for alpha amino acids
Proline
GABA
Beta alanine
Classification of aa(4)
Structure
Side chain
Metabolism
Nutritional requirements
Simple
Glyicine
Alanine
Branched chain
Valine
Leucine
Isoleucine
Hydroxy aa
Serine
Threonine
S containing
Cysteine
Methionine
Amide group
Asparagine
Glutamine
Monoamino dicarboxylic
Aspartic acid
Glutamic acid
Dibasic monocarboxylic
Lysine
Arginine
Aromatic
Phenylalanine
Tyrosine
Heterocyclic
Tryptophan
Histidine
Imino acid
Proline
DERIVED AA
found in proteins
Hydroxy proline and hydroxy lysine-
Important components of collagen
Gamma carboxylation of glutamic acid residues of proteins - important for clotting process
Ribosomal proteins and histones - aa ext methylated and acetylated
Not seen in proteins
During metabolism of proteins
Orinithine
Citruline
Homocysteine
Thyroxine may be considered as derived from tyrosine
Non alpha aa
Gaba - glutamic acid
Beta alanine - pantothenic acid n coA
Special groups
ARGININE
PHENYLALANINE
TYROSIN
TRYPTOPHAN
HISTIDINE
PROLINE
GUANIDIUM
BENZENE
PHENOL
INDOLE
IMIDAZOLE
PYRROLIDINE.
Non polar side chain
Polar.
Uncharged /nonionic
Polar.
Charged/ionic
Purely ketogenic. Why
Leucine.
Because leucine is converted to ketone bodies during metabolism
Keto and gluco. (5)
Lysine
Isoleucine
Phenylalanine
Tyrosine
Tryptophan.
In humans lysine predo ketogenic
During metabolism part of carbon skeleton of these aa will enter ketogenic pathway and other half glucogenic pathway
Purely glucogenic
All the 14 remaining.
Enter only into glu path
Essential/ indispensable
Partially/semi essential/ semi indespensable
Non essential/ dispensable
Tasteless
Leucine
Bitter
Isoleucine
Arginine
Flavouring agent
Sodium glutamate
Artificial sweetner. Contains
Aspartame
Aspartic acid phenylalanine
MP
Solubility
High. > 200c
Soluble in polar. Insoluble in non
Sweet
Amoholyte
Aa can exist as ampho or zwitter ions in soln depending on the ph of the medium
Isoelectric point(4)
The ph at which the molecule carries no net charge is knows as
In acidic solution they are cationic form and in alkaline behave as anions
At iso aa will carry no net charge all the groups are ionized but the charges will cancel each other
Therefore at at this point
No mobility in an E
Solubility minimum
Buffering capacity minimum
Buffering action!!
At isoelectric point minimum
Maximum in and around pk1 or pk2
Optical activity (3)
Aa having an assymetric C atom exhibits OA
Glyicine simplest aa. No assymetric c atom. Shows no OA
All others are O active
Optical isomers / mirror image forms produced with reference to alpha carbon atom
Which occurs naturally
D and L.
L isomers - natural aa
D aa are seen in
Small amounts in
Microbes and constituents of certain antibiotics such as
GRAMICIDIN - S
POLYMYXIN
ACTINOMYCIN -D
VALINOMYCIN
bacterial cell wall peptidoglycans
Isoleucine and threonine OA
2 optically active centres
4 diastereo isomers
Optical isomers are used extensively in medicine. Explain
Approx 50% of marketed drugs are chiral
2 forms must be distinguished because they may differ in dosages effectiveness side effects and indicated use
Examples
Ethambutol
1- treat tuberculosis
1- cause blindness
Naproxen
1- treatment for arthritis
1- liver poisoning
General reactions of aa
Due to carboxyl group (2)
Due to amino group(3)
Due to side chains(4)
Decarboxylation(3)
The amino acids will undergo
alpha decarboxylation to form the corresponding amine
Thus some important amines are produced
from amino acids.
For example,
Histidine → Histamine + CO2
Tyrosine → Tyramine + CO2
Tryptophan → Tryptamine + CO2
Lysine → Cadaverine + CO2
Glutamic acid → Gamma amino
butyric acid (GABA) + CO2
Amide formation (4)
The -COOH group of
dicarboxylic amino acids (other than alpha
carboxyl) can combine with ammonia to form the
corresponding amide.
For example,
Aspartic acid + NH3 → Asparagine
Glutamic acid + NH3 → Glutamine
These amides are also components of protein
structure.
The amide group of glutamine serves
as the source of nitrogen for nucleic acid synthesis.
Transamination(3)
The alpha amino group of
amino acid can be transferred to alpha keto acid to
form the corresponding new amino acid and alpha
keto acid.
This is an important reaction
in the body for the inter-conversion of amino acids
and for synthesis of non-essential amino acids.
Ast increases in MI
Alt increases in liver disease
Oxidative deamination(2)
The alpha amino group
is removed from the amino acid to form the
corresponding keto acid and ammonia
In the body Glutamic acid is the most common
amino acid to undergo oxidative deamination.
Transdeamination(3)
Most of the aa transfer their amino group to alpha keto glutaric acid to form glutamic acid.
Glutamic acid undergoes oxidative deamination to release ammonia.
The two reactions are metabolically coupled
Formation of carbamino compound (3)
Carbon
dioxide adds to the alpha amino group
of amino acids to form carbamino compounds.
The reaction occurs at alkaline pH and serves as
a mechanism for the transport of carbon dioxide
from tissues to the lungs by hemoglobin
Hb—NH2 + CO2 →
Hb—NH—COOH (Carbamino-Hb)
Transmethylation(2)
The methyl group of Methionine,
after activation, may be transferred to an acceptor which
becomes methylated
Methionine + Acceptor → Methylated Acceptor +
Homocysteine
Ester formation by OH group(3)
The hydroxy
amino acids can form esters with phosphoric acid.
In this manner the Serine and Threonine residues
of proteins are involved in the formation of
phosphoproteins.
Similarly these hydroxyl groups
can form O-glycosidic bonds with carbohydrate
residues to form glycoproteins.
Reaction of the amide group (1)
The amide groups
of Glutamine and Asparagine can form N-
glycosidic bonds with carbohydrate residues to form
glycoproteins.
Reactions of SH group (3)
Cysteine has a
sulfhydryl (SH) group and it can form a disulphide
(S-S) bond with another cysteine residue.
The two
cysteine residues can connect two polypeptide
chains by the formation of interchain disulphide
bonds or links
The dimer formed by
two cysteine residues is sometimes called Cystine
or Dicysteine.
Which structure of protein is responsible for biological activity?
Primary? In text
Domain (11)
Compact globular functional unit of protein
Relatively independent region of protein and may represent a functional unit
Defined as stable units of protein structure that could fold autonomously
Each domain forms a compact 3 dimensionsal structure
Molecular evolution uses domains as building blocks
Domains vary in length from between 25 to 500 aa.
Domains are stabilised by metal ions or disulphide bridges
Provide specific catalytic binding sites as found in E or regulatory proteins
Usually connected w relatively flexible areas of protein
Immunoglobulin contains specific domains
Form functional units such as calcium binding domain of calmodulin
PRIMARY STRUCTURE (4)
BRANCHED AND CIRCULAR PROTEIN
Denotes the no. And sequence of aa in the protein
Higher levels of organisation are decided by the primary structure.
Generally polypeptide chains are linear
Branching points may be produced due to interchain disulfide bridges
Interchain and intrachain
Very rarely protein maybe present in circular form eg Gramicidin
Each polypeptide chain has a unique amino acid sequence decided by genes
Primary structure maintained by covalent peptide bonds.
Pseudopeptide / isopeptide
Gamma carboxyl group of glutamic acid may enter into peptide formation
Eg Glutathione ( Gamma glutamyl cystenyl glyicine)
MOTIF
In a Protein a structural motif is a superstructure
Found in proteins and E with dissimilar functions
Two proteins may share the same motif yet lack appreciable primary structure similarity
Examples :
Beta hairpin
Helix loop helix
Zinc finger
Helix turn helix
Formation of ammonia
Liberated from aa and nitrogenous compounds
produced in intestine by bacteria metabolism and also in kidney for maintenance of extra cellular ph
at physiological ph NH4+ formation is favoured by a factor of 100:1.free ammonia can diffuse across membranes but not NH4+
first step in catabolism of aa is to remove amino group as ammonia. this is the major source of ammonia.
small qties from catabolism if purine and pyramidine bases
highly toxic to nervous. detoxification is by conversion to urea and ex through urine
Source and fate of ammonia
Transamination
Reaction
E
Prosthetic group
Rever/irrever
Example
Exchange of alpha amino group between one alpha amino acid and another alpha keto acid forming a new alpha amino acid
.aa1 + ka2 = aa2+ ka1
Aminotransferases
Plp
Readily reversible
.
Biological significance of transamination (3)
Exception
First step of catabolism
NH3 removed and carbon skeleton of aa enters into catabolic pathway
Synthesis of non essential aa
From keto acids
Pyruvate (t) alanine
Oaa aspartic acid
Alpha getoglutarate glutamic acid
Interconversion of aa
Lysine threonine and proline are not transaminated. They follow direct degradative pathways.
Clinical significance of transamination
Ast and alt are induced by glucocorticoids which favor gluconeogenesis
Markers of liver injury
