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Cells to systems (Dr Lee Bantings lectures) (Proteins (Elements getting…
Cells to systems (Dr Lee Bantings lectures)
Carbohydrates
Carbohydrates can be un-naturally linked to proteins resulting in glycated proteins – this is where monosaccharides, in particular glucose, can react chemically with amino acids directly often under oxidizing conditions
Glycated human haemoglobin
The derivatisation of haemoglobin by glycation via diabetes linked oxidative stress. This is used as a biochemical marker for diabetes.
Carbohydrates can naturally be linked to proteins resulting in glycosylated proteins – this occurs by enzymatic processing
A cluster of sugar residues linked to the protein
via an enzymatically mediated amino acid
derivitization, a post-translational glycosylation of the –OH of a serine or threonine.
Carbohydrates can naturally be linked to aglycones in nucleic acid bases, lipids, natural products etc. often through an anomeric link to other heteroatoms
‘Polysaccharide’ (a glycan) is the name given to a macromolecule consisting of a large number of monosaccharide (glycose) residues joined to each other by glycosidic linkages.
A well known example of a polysaccharide is glycogen – a branched α- anomeric linked polyglucose. Iodine can stain these polymers.
Another example of a disaccharide is sucrose – a disaccharide formed in nature enzymatically from a unit of glucose (a hexose) joined via an α-anomeric bond from the glucose to the β-anomeric position on fructose (a pentose) via condensation.
β-maltose is an α(1->4) glucoside found in corn syrup, broken down in the body into glucose by maltase. β-lactose (a β(1->4) glucoside) is 4-6% cow’s milk and 5-8% of human milk. Lactose intolerance can occur due to the lack of the enzyme lactase that breaks lactose down into galactose and glucose by hydrolysis.
Oligosaccharides are compounds in which monosaccharide units are joined by glycosidic linkages. According to the number of units, they are called disaccharides, trisaccharides, tetrasaccharides, pentasaccharides etc.
An example of a disaccharide is maltose – a disaccharide formed in nature enzymaticaly from two units of glucose joined with an α(1→4) bond via condensation but with variation in the terminal anomeric position.
The generic term ‘monosaccharide’ (as opposed to oligosaccharide or polysaccharide) denotes a single unit, without glycosidic connection to other such units.
A well known example of a monosaccharide is glucose – a white crystalline solid, soluble in water and some organic solvents, interacts with plane polarized light
Carbohydrates received their name, historically, from the fact that monosaccharides often have a general formula Cm(H2O)n
Nucleic acids
DNA melting
For the same length (no. of base pairs) of DNA the “melting point” depends on the GC/AT ratio of the sequence of DNA. Other factors such as pH and presence of denaturants such as urea may have an effect on denaturation. Melting can be monitored using UV spectroscopy and the process can be reversible.
DNA super coiling:
Histones are +ve charged proteins that aid the coiling process and ion pair with the polyanionic DNA
DNA vs RNA:
The presence of a hydroxyl group at the 2' position of the ribonucleotide sugar in RNA distinguishes it from DNA. This functional group causes any double helical regions to prefer an A-form geometry rather than the B-form most commonly observed in DNA.
This also results in a very deep and narrow major groove and a shallow and wide minor groove. An important secondary consequence is that it also introduces extremely conformationally flexible regions within RNA when these regions are often not paired in a stable double helix. This introduces hairpin loops bulges and internal loops. Very unlike DNA.
DNA structure:
-DNA (DeoxyriboNucleic Acid), a relatively water soluble polymeric polyanion
Phosphate – sugar backbone
negatively charged phosphates
Sodium cations as positive counterions
Specific DNA base pairs linked by strong hydrogen bonding
double helical shape
Nucleic acids are biological molecules essential for known forms of terrestrial life, they include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Alongside proteins, nucleic acids are one of the most important class of biological macromolecules; each type is found in abundance in nearly all living things, where they function in encoding, transmitting and expressing genetic information.
RNA types:
RNAs involved in protein synthesis
mRNA – messenger RNA that carries genetic code from DNA to the ribosome
tRNA – transfer RNA moves specific amino acids to the growing polypetide chain at the ribosome
rRNA – ribosomal RNA is a structural element of the ribosome that facilitates the reading of the mRNA and catalyses peptide bond formation of the growing chain
RNAs involved in post-transcriptional modification
Signal recognition RNA – directs trafficking of protein and is involved in secretion
Ribonuclease P – a complex RNA that acts as a ribonuclease (yes, an enzyme!!) that cleaves RNA
RNAs involved in regulatory processes
Antisense RNA – single stranded RNA complementary to mRNA that inhibits translation
Long non-coding RNA - long ncRNAs are often considered as non-protein coding transcripts longer than 200 nucleotides that modulate the function of transcription factors by several different mechanisms, including functioning itself as a co-regulator, modifying transcription factor activity, or by regulating the association and activity of co-regulators.
Small interfering RNA (siRNA) - aka: short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that are involved in an RNA interference (RNAi) pathway modulating the expression of a specific gene
MicroRNAs (miRNA) – are post-transcriptional regulators that bind to complementary sequences in the three prime un-translated regions (3' UTRs) of target messenger RNA transcripts (mRNAs) more often than not resulting in gene silencing
Proteins
Elements getting together:
3o - Tertiary structural characteristics can be (i) experimentally detemined by x-ray diffraction or spectroscopic techniques such as NMR or (ii) predicted by various methods of comparison with proteins of known structure (colour coded in a molecular visualization software from blue (amino terminus) to red (carboxyl terminus)
Holding hands:
4o - Quaternary structural characteristics can be determined by various biophysical techniques (e.g. methods that measure mass of intact complex directly, sedimentation-equilibrium analytical ultracentrifugation, electrospray mass spectrometry) or (ii) predicted by docking 3D models of proteins with one another
Building blocks:
Proteins are condensation polymers comprising amino acids. The sequence of the amino acids specify the form and thereby the function of the resultant compound.
Protein tenancies:
2o- Secondary structural characteristics can be predicted by various methods of comparison with a set of proteins of known structure (as determined by x-ray diffraction analysis of their crystals) – the position of an amino acid, its relationship to its neighbours and what tertiary characteristics – helix, β-sheet etc.
Building of a tripepetide:
The backbone of the emerging oligopeptide and the side chains of their residues have to find a ‘comfortable’ conformation. This begins to form a tertiary structure. The steric bulk, charge and h-bonding capacity of the side chains all play a role.
Gene to protein:
Proteins are condensation polymers comprising amino acids. The sequence of the amino acids specify the form and thereby the function of the resultant compound.
Proteins going round the bend:
Human serum albumin – a change in direction between two helical regions. A glycine residue can facilitate this due to the lack of a side chain, a chain breaker.
A protein is a linear polymer built from about 20 different amino acids. The type and the sequence of amino acids in a protein are specified by the DNA in the cell that produces them. This sequence of amino acids is essential since it determines the overall structure and function of a protein.
Back around the bend:
Human serum albumin – a change in direction between two helical regions. A proline residue can facilitate this due to the amino and carboxyl group being fixed within a ring, it is a known chain breaker.
Pleats:
Bacterial catalase – a different motif known as beta-pleated sheets can occur to form a rigid structure for function
Cofactors:
P450s – an enzyme class that metabolizes drugs by utilising oxygen
Kinases – an enzyme class that phosphorylates substrates to switch them on or off
An apoprotein (apoenzyme) is the name given to a protein (holoprotein, holoenzyme) that doesn’t hold the cofactor
Lipids
Lipids – phospholipids
made up of glycerol, two fatty acyl units and a phosphate(alcohol) unit
Lipids – plasmalogens
made up of glycerol, fatty alcohol unit linked by ether, fatty acyl unit and a phosphate(alcohol) unit
Platelet Activating Factor (PAF) - Inflammation and immune mediator – responsible for platelet aggregation, anaphylactic shock. This is just one example of a lipid acting as a signaling molecule, there are many more. When these compounds are membrane derived this indicates that membranes are ‘active’ entities not just physical barriers.
Lipids - triacylglycerols
made up of glycerol and three fatty acyl units
Lipids – sphingolipids
made up of Sphingosine, hydroxyl, fatty acyl amido unit and a phosphate(alcohol or glycoside)
Lipid Classes
Hydrolysable
CHO
Triacylglycerols
animal
Vegetable
waxes
CHOPN
esters of glycerol
Phosphatides
Plasmalogens
non-hydrolysable
steriods
Esters of sphingosine
Sphingomyelins
Cerebrosides
terpenes
others
Lipids – cerebrosides
made up of Sphingosine, hydroxyl, fatty acyl amido unit and a phosphate(alcohol or glycoside)
Lipids – steroids
DMAP = dimethyl allyl pyrophosphate
IPP = iso-pentenyl pyrophosphate
GPP = geranyl pyrophosphate
A loosely defined term for substances of biological origin that are soluble in nonpolar solvents. They consist of saponifiable lipids, such as glycerides (fats and oils) and phospholipids, as well as non-saponifiable lipids, principally steroids.
Steroid family including:
Glucocorticoids; e.g. cortisol, the major representative in most mammals
Mineralocorticoids; e.g.aldosterone being most prominent
Androgens; e.g. testosterone
Estrogens;
e.g. estradiol and estrone
Progestogens; (aka: progestins)
e.g. progesterone