WEEK 3 Flashcards
How many amino acids are proteins derived from?
20
What was the first and last amino acid to be found?
Asparagine in 1806 and Threonine in 1938
Describe the structure of amino acids
Amino acids contain an amino group, carboxyl group, H atom and a variable group (side chain) attached to a central carbon atom
What are the two types of amino acids and how are they determined?
There are D and L amino acids
The amino acid having the NH2 group on the right is called D-amino acid and the amino acid on the left is called L-amino acid
What is pKa?
Pka is the log acid dissociation constant. Pka is a number that describes the acidity of a particular molecule and measures the strength of an acid by how tightly a proton is held by a Bronsted acid.
The lower the value of pKa, the stronger the acid and the greater its ability to donate its protons.
What is the normal plasma pH?
7.35-7.45
The amino acid charge depends on _____ values
pKa
What are the properties of Basic amino acids?
- +1 charge at normal pH
- Remove H+ from solution
- Raise pH
What are the properties of histones?
- Contain basic amino acids
- High content of lysine & arginine
- Positively charged
- Binds to the negatively charged phosphate backbone DNA
What is the main amino acid in collagen?
Proline
What are the properties of acidic amino acids?
- -1 charge at normal pH
- Dissociate H+ into solution
- Decrease pH
List examples of hydrophobic amino acids
- Proline
- Methionine
- Alanine
- Glycine
- Tryptophan
- Leucine
- Phenylalanine
- Caline
- Isoleucine
What are the properties of non-polar, aliphatic R groups?
- R groups are non-polar and hydrophobic
- Side chains of alanine, valine, leucine and isoleucine tend to cluster together with proteins which stabilises protein structure through the hydrophobic effect
What are the properties of Glycine?
- Has the simplest structure
- Non-polar amino acid
- Has a very small side chain so no real contribution to hydrophobic effect
What are the properties of Methionine?
- One of the two sulfur-containing amino acids
- Slight non-polar thioether group in its side chain
What are the properties of Proline?
- Aliphatic side chain with distinctive cyclic structure
- The secondary amino acid group of proline residues is held in a rigid conformation that reduces the structural flexibility of polypeptide regions containing proline
- Main amino acid in collagen
- Non-polar
What are the properties of Polar, uncharged R groups?
- R groups are more soluble in water/more hydrophilic
- Contain functional groups that form hydrogen bonds with water
List examples of polar amino acids
- Serine
- Threonine
- Cysteine
- Asparagine
- Glutamine
The polarity of serine and threonine is contributed by their _______________
Hydroxyl groups
The polarity of asparagine and glutamine is contributed by their ______________
Amide groups
What substitution of amino acids results in sickle cell anaemia?
Substitution of polar Glutamate for non-polar Valine in the haemoglobin protein
What is the difference between Glucogenic and Ketogenic amino acids?
- Glucogenic amino acids can be converted to pyruvate or TCA cycle intermediates whereas ketogenic amino acids convert to ketone bodies and acetyl CoA
- Glucogenic can become glucose via gluconeogenesis whereas ketogenic cannot become glucose
Most amino acids are either ________ or ___________________
Glucogenic
Glucogenic & Ketogenic
Define the ‘Primary structure of a protein’
The linear sequence of amino acids
What is the name of the region in which different amino acid residues are tolerated at a position?
Hypervariable
What is the name of the regions that form binding sites or are critical for forming a functional three-dimensional structure with exactly the same amino acid sequence?
Invariant regions
What does polymorphism in protein structure generally arise from?
Mutations
What is the difference between foetal haemoglobin and adult haemoglobin?
Hemoglobin (Hb) is expressed as the fetal isozyme HbF during the last trimester of pregnancy until after birth, when it is replaced with HbA.
Describe the structure of foetal haemoglobin?
HbF is composed of two hemoglobin α and two hemoglobin γ polypeptide chains, in contrast to the adult hemoglobin, hemoglobin A, which has two α- and two β-chains
During which stages of development are chains with a different amino acid composition (ε- and ζ-chains) produced?
Embryonic stages of development
The differences arise evolutionarily from mutation of which genes to produce ζ and ε?
These differences are believed to arise evolutionarily from mutation of a duplicated α gene to produce ζ, and mutation of a duplicate β gene to produce ε
The foetal and embryonic forms of haemoglobin have a have a much _______ affinity for O2 than the adult forms and thus confer an advantage at the low O2 tensions to which the foetus is exposed
higher
Define ‘Tissue-specific isoforms’ or ‘isozymes’
Proteins that differ somewhat in primary structure and properties from tissue to tissue but retain essentially the same function
Isozymes are each composed of two subunits with how much homology (similarity between sequences)?
60% to 72%
What is an example of a protein that exists as tissue-specific isozymes?
The enzyme creatine kinase (CK)
Describe the function of creatine kinase (CK) in the body
There is sequence homology (similarity between sequences) of the two creatine kinases that bind to the muscle sarcomere; the M form is produced in skeletal muscle and the B polypeptide chains are produced in the brain. Protein is composed of two subunits therefore the skeletal muscle produces an MM creatine kinase and the brain produces a BB form.
The heart produces both types of polypeptide chains and therefore forms a heterodimer (MB) as well as the homodimers
After synthesis of a protein has been completed, a few amino acid residues in the primary sequence may be further modified in ______________ reactions that add a chemical group _______ or otherwise modify specific amino acids in the protein
Enzyme-catalysed
Oxidise
How many different post-translationally modified amino acid residues have been found in human proteins?
100
What is ‘Glycosylation’?
The addition of carbohydrates to a molecules
What is the difference between O-glycosylation and N-glycosylation?
In O-glycosylation the carbohydrates are bound to serine or threonine residues in proteins by O-linkages. In N-glycosylation the carbohydrates are bound by N-linkage to the amide nitrogen of asparagine
What is ‘Fatty acylation’?
The addition of lipids to a molecule
What are some example of fatty acylation?
Palmitoyl groups (C16) are often attached to plasma membrane proteins and the myristoyl group (C14) is often attached to proteins in the lipid membranes of intracellular vesicles
What does phosphorylation, acetylation and adenosine diphosphate (ADP)-ribosylation of a specific amino acid do to that protein?
It alters the bonding and changes the activity of the protein
Describe how the post-translational modifications of collagen gives it its character
Collagen is an abundant fibrous extracellular protein that contains the oxidised amino acid hydroxyproline. The addition of the hydroxyl group (hydroxylation) to the proline side chain provides an extra polar group that can engage in hydrogen bonding between the polypeptide strands of the fibrous protein and stabilise its structure
What is the condition “Cystinuria”?
a hereditary defect of renal PCT and intestinal amino acid transporter that prevents the reabsorption of Cystine, Ornithine, Lysine and Arginine. The excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stones.
What does Cystine consist of?
2 cysteines (an amino acid) connected by a disulphide bond
What is the treatment for Cystinuria?
- Urinary alkalisation and chelating agents increase the solubility of cystine stones
- Good hydration
- Diet low in methionine
How is Cystinuria diagnosed?
Cystinuria is detected with urinary sodium-cyanide nitroprusside test and proton nuclear magnetic resonance spectroscopy of urine
