Biochemistry - Lecture notes 1-4 PDF

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Chem 271- notes for lecture 1-4...

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Hydrophobic amino acids (8) Take away from lecture It's not polar and not charged. Some are more hydrophobic. One hydrogen is less hydrophobic than an R group with 4 carbons. Tryptophan and phenylalanine are aromatic Isoleucine has two chiral carbons. Take away from reading The simplest amino acid is glycine which has a single Hydrogen Atom and it has a chain. Glycine is unique in being achiral due to the two hydrogen Atoms bonded to the alpha carbon atom. Polar amino acids (6) Take away from lecture Threonine Has 2 chiral carbons Tyrosine is aromatic. Cysteines has a specials role due to its -SH bond. Take away from reading The hydroxyl group makes these amino acids much more hydrophilic water loving and reactive than they are hydrophobic analogs. Cysteine contains A Sulfhydryl group instead of a hydroxyl group. This group is much more reactive. Pairs of sulfhydryl groups may come together to form sulfhydryl bonds which are very important in stabilizing some proteins. Positively charged amino acid (3) Lysine switches from -NH2 to -NH3+ Arginine has a shared charge, so it fluctuates between two nitrogen Histidine the nitrogen can pick up a hydrogen and become positive pka →the fact that these R groups can be charged depends on the pka of the group Lisine and arginine has high pka Histidine has a special Take away from reading Positive charges on amino acids render them highly hydrophilic. Negatively charged amino acid (2) Their side chain usually lack a proton that is present in the acid form and hence or negatively charged. nonetheless in some proteins These side chains do accept protons and this ability is often functionally important.

2.2 primary structures; amino acids are linked by peptide bonds to form a polypeptide chains -

Linked polymers polymers are formed by linking the alpha carboxyl group of one amino acid to the alpha amino group of another amino acid.

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This bond between two amino acid is accompanied by a loss of a water molecule. Biosynthesis of peptide bonds requires an input of free energy. The rate of hydrolysis in a peptide bond is extremely slow. - Polypeptide chain equals a series of amino acids attached by peptide bond. - A polypeptide chain has polarity because it’s ends are different. There is one carboxyl group at the terminus Side of the polypeptide chain where as there is an amine group at the beginning of the polypeptide chain - The polypeptide backbone is rich in hydrogen bonding potential‘s. Each residue contains a carbonyl group C double bond oh which is a good hydrogen bond acceptor and with the exception of proline on an age group which is a good hydrogen bond donor. These groups interact with each other and with functional groups from side chains to stabilize particular structure Proteins have unique amino acid sequence specified by Genes - The amino acid sequence of a protein is referred to as two is as its primary structure Polypeptide chains are flexible yet conformationally restricted - The peptide bond is essentially planar - Because of the double bond character rotations in bond is prevented that’s the confirmation of the peptide backbone is constrained - Two configurations are possible for the planar peptide bond: The trans and cis. Configuration - In the sis configuration the our groups are on the same site which is why trans configurations are preferred. Almost all peptide bonds in proteins are trends. The steric clashes between groups attached to the alpha carbon when hinders the formation of the cysts form -

September 17, 2020 Primary Structure The polypeptide backbone → n terminal has a to c terminal (N-C-C) → the difference between N terminal and the c terminal, the N terminal having a free amine group and the C terminal having a free carboxyl group. → the amine group, the alpha carbon and the carbonyl group are all covalently joined. Covalent bonding between cysteines → covalent bond not necessarily found in the backbone → cysteine has specific properties 1. Form disulfide bonds Forms a covalent bond with another cysteine’s -SH group, making a disulfide bridge. This is an oxidation process, by forming the disulfide bond we are removing 2H+ and 2e-.If we want to break the bond, we have to add 2 electrons #reduction. The peptide bond has a planar character → the planar character is between the one alpha carbon and another alpha carbon →The polypeptide is automatically going to be in a certain fold to accommodate these panes. → Why are they planar? It's because of the resonance structure that can be formed between peptide bonds.

→ this means that there is no rotation around the peptide bond. The only rotations allowed are around the alpha carbon. We can have rotation between the amine group the alpha C. That rotation angle is called phi (𝜱) . We can also have rotation between the alpha C and the carbonyl group. This rotation angle is referred to as psi (𝝍).

→ “Dihedral” or “torsion” angles define the degrees of rotation. According to the Ramachandran plot, he figured out that only some conformations are allowed, due to steric hindrance. Depending on the R group, you can see different kinds of steric hindrance. Amino Acid sequence defines 2nd and 3rd structure → The sequence of amino acids is important because it determines how the protein will fold.

Typical bond lengths within a peptide unit

Peptide bonds can be “cis” or “trans” → in the trans conformations, the R group poin in the opposite direction. This configuration predominantes, because the cis configuration leads to more steric hinderance. → In the cis conformation, they are pointing in the same direction, towards eachother. → Proline is an exception. Proline is an amino acid that forms covalent bonds with itself. The last carbon in the side chain forms a covalent bond with the amine group in the side chain. So in the cis and trans configuration there will be steric hindrance and neither is favored. Secondary structure The alpha helix → H-bonds keeps the helix together → Carbonyl groups form a H-bond with the amine group further away. →The amino acid R group points out from the alpha helix. By looking at the properties of the side chains, we can see how the helix will behave. If all the side chains were hydrophilic, we would have a completely hydrophilic alpha helix. → We can also have some R groups that are hydrophilic and some that are hydrophobic, from the same peptide chain. → Most alpha helices are mostly right-handed, but can also be found in the left handed (small nb) → H-bonds forming in between every fifth amino acids (each turn is 5.4Å #pitch) (3.6 amino acids per turn).

Certain amino acid r group destabilize alpha helices → Valine (V), theonine (T) and isoleucine (I) with bulky groups at the ฀-carbon tend to destabilize 𝛼-helices because of the steric clashes. → Serine (S), aspartate (D) and asparagine (N) side chains contain H-bond donors or acceptors that are close to the main chain, where they can compete for main chain NH and CO groups. → proline (P) also is a helix breaker because the ring structure of its side chain blocks the NH group and does not allow the 𝜱 value required to fit into an 𝛼-helix. The beta strands → much more extended in space than a helix → H-bonds also stabilizes by H-bonds interaction between beta strands

September 29, 2020 Evolutionary relationship → the primary sequence is different then they are not at all evolutionarily correlated. → They are not in the same order shows that they are not from the same origin, Oxygen binding proteins Myoglobin and hemoglobin → Hemoglobin: blood O2 and CO2 carrier Goes from lungs to parts of the body and returns CO2 to the lungs. → hemoglobin is found in the red blood cell → Myoglobin: Muscle O2 reservoir → is a monomer Why do we need O2?

October 1, 2020 Compounds that change binding properties of hemoglobin 2-3-bisphophate Without having 2-3-bisphophate attached to hemoglobin, hemoglobin is not able to release as much oxygen as it normally does How can it bind to hemoglbin and have such a large effect, when the structure hads nothing in common with oxygen? One 2,3-bpg stabilizes one whole ass tetramer → the residues in the histidine and lysine amino acid have positively charged amino acids, and bpg is negatively charged making a stable structure. → fetuses have different hemoglobin structure because they need binding efficiency more o2. They’re structure is 2 alpha subunit and 2 gamma subunit, whereas for adults, its 2 beta and 2 alpha subunit. Carbon monoxide → Carbon monoxide also binds to hemoglobin → CO binds to heme the same way O2 does, but it has a stronger affinity (200 times stronger) → When CO binds to heme it shifts the T state to R state. Bohr effect → When we exercise, - pH drops from 7.4 to 7.2, because our blood becomes acidic due to the increase of lactic acid. - We increase H+ concentration - We increase the levels of CO2 because carbohydrates are degraded to produce energy and the products are CO2 - Exercising tissues have a higher demand for O2 → pH and [CO2] contributes to the Bohr effect → The Bohr effect leads to more release of O2 in the tissues → CO2 binds to the amine terminal and not the heme group.

Different hemoglobins → Sickle cell anemia is caused by a genetic defect that alters Hb structure. They are blood cells which are not the right shape so they have a hard time circulating in the blood: - Clog arteries - Hinder blood flow - Painful swelling - Leads to high risk or strokes and infection → there is a link between sickle cell anemia on one dna allele protecting u from malaria, since malaria affects the red blood cell Diseases associated with hemoglobin Thalassemia → different types of mutation leads to this diseases There are two main group 1. Alpha-thalassemia Not enough alpha chain made, beta chain form tetramer with no cooperativity, which leads to poor efficiency of oxygen carrier 2. beta-thalassemia

Exploring proteins → purification of proteins

October 6, 2020...