Chapter 12 Flashcards
Basis for Vitamin C deficiency
- has a triple helix of collagen and is a protein in a protein
- has prolyl hydroxylase - with hydroxiproline each O-H can actually for the make hydrogen bonds between the helices
- without the H - bonds, the collagen is less stable - vitamin c is a co-factor enzyme of prolyl hydroxylase or proline
- people with a deficiency have everything they need, but the prolyl hydroxylase can’t function properly with a lack of vitamin C in the body
What happens in cells that run out of oxygen?
Glycolysis can still occur
Keq is the concentration of [AB]/[A]*[B]
- if everything is stable then it is at equilibrium
- at equilibrium, the rate of the forwards and backwards is the same
- the concentration of A to B must be equal, but does not have to be equal to each other
[AB] is rarely = [A] = [B]
What is a strong acid
- something that dissociates completely
- strong acids have irreversible dissociations
What is a weak acid?
- will have a undissociated acid and a conjugate base
- weak acids have reversible dissociation
How can we tell which type of acid we are dealing with
- if given a Ka for an acid it is a weak acid because strong acids do not have Ka’s (this is because they are completely dissociated)
Some acids do not dissociate completely. Instead what do they do?
They only dissociate partially, so over time there are constant amounts of protons and undissociated acid
As you add a base to a solution what happens
As you add base the solution you release/remove protons causing it to increase and dissociate more
The higher the mili mole is what happens
- the higher the mili mole goes the more acidic it is. This means that the higher the mM the lower the pH should get
A strong acid will what compared to weak?
A strong acid will be more acidic, will dissociate more, and will have a lower pH than weak acids
At 1/2 equivalence what happens
AH = [A^-]
- this is important because if pH = pKa which = -log (pKa)
- when you dissociate half the acid the undissociated acid and coagulate bases are equal
[AH] = [A^-] -> effective buffer
How do you know if something is an effective buffer?
If OH^- is added, AH + OH -> A^- + H2O
If H^+ is added, A + H -> AH
- it is an effective buffer if the pH is minimal or has no change
How to determine the pH of a strong acid that has dissociated completely
PH = -log [H+]
Define affinity
- affinity is one of the most important measurements of a drug binding to a target
How do receptor blockers work
- molecules that are designed to bind a specific receptor should resemble the hormone that naturally binds that receptor
- the set of characteristic that determine the binding of a drug to the receptor is called the pharmacophores
- affinity is one of the most important measurements of a drug binding to a target
Competitive inhibition of binding
- naloxone is a competitive inhibitor of oxymorons and morphine, it competes for binding to their opioid receptors
- although fentanyl does not look like this, it is an even more potent opioid. There are several opioid receptors and fentanyl does not bind with the same affinity to the same morphine-binding receptors
Difference between affinity and specificity
Affinity tells how strong the interaction is
Specificity tells how something is selectively achieved
How does aspirin work?
- Hormones, our chemical messengers, are produced by the body’s endocrine glands.
- Hormones encompass a wide range of functions and a similarly wide range of chemical composition and structure.
- Enzymes are proteins and/or nucleic acids that act as biochemical catalysts, influencing (mostly accelerating) the rates of chemical reactions.
- Aspirin works by inhibiting the cyclooxygenase enzymes COX1 and COX2. These enzymes participate in the prostaglandin synthesis pathway. Prostaglandins are responsible for fever, swelling, increased sensitivity of pain receptors, inhibition
of blood vessel dilation, and the production of stomach acid and mucus.
What is Kd
The dissociation or the direct reciprocal of Keq
The strength of the receptor does what
The strength of the receptor gives the amount of RD and RH
- the higher the affinity will likely win
What is a pharmacophore
The portions of a molecule(s) that interacts with the cellular target
When RH comes together in Keq it does what
It is a competition between them
- in order to compete, whatever is competing for the binding of the receptor must be the same shape.
- if you have a natural substrate or a cognate the other one competing must be a competitor/competitive inhibitor
Chiral isomers
Chiral isomers have the same chemical formula, but they differ in the arrangement of atoms around at least one atoms, which is called the chiral center
- often, the chiral center is a carbon atom. For a carbon to be a chiral center it has to have 4 different atoms (or groups of atoms) around it
Biological systems and chiral molecules
- biological systems often discriminate among chiral molecules, preferring one enantiomer over another. Amino acids and sugars have chiral centers, and living systems usually can use only one enantiomer not both. Levomethorphan is an opiate.
Dextromethorphan is a non-addictive cough suppressant
Most abundant steroid
The most abundant (and much maligned) steroid is cholesterol. It is made of 4 non-polar rings and is a C3 hydroxyl group
Cholesterol functions as a precursor to steroid hormones
- Glucocorticoids affect many biological functions including inflammatory responses, mental stress management, and carbohydrate, protein, and lipid metabolism. Example: cortisol.
- Aldosterones and mineracorticoids regulate salt balance, including excretion of salts by
the kidneys. - Androgens and estrogens regulate sexual development and function.
Examples: testosterone, b-estradiol (estrogen), progesterone.
Diseases associated with steroid malfunction
- Vitamin D is a cholesterol derivative. The various forms of vitamin D, especially D2 and D3, regulate calcium absorption from food. Vitamins D2 and D3 are formed by exposure to sun light (although sun light does not contain vitamin D), which triggers a non-enzymatic conversion of a cholesterol derivative into vitamin D precursors. These precursors then become hydroxylated, thereby activated, in the kidneys and liver.
•In the absence of adequate amounts of active vitamin D, calcium cannot be absorbed efficiently from the diet, and this results in a disease called rickets. Rickets is characterized by bone malformation, bone softness, and tooth brittleness.
•Excessive vitamin D can cause high serum calcium levels, which can lead to kidney stones, kidney failure, and calcification of soft tissue. It has been suggested that the increase in skin
pigmentation in populations leaving near the equator is a protective mechanism against excessive absorption of vitamin D.
when solving for Keq how do you know what is the product and what is the reactant
the right side is always the product and the left side is always the reactant
when pH is equal to pKa what are AH and A-
when the pH is equal to pKa the AH and A- are equal
- if the pH is 7.5 then only A- would be present
- if the pH is 3, then only AH would be present
4: The pKa of a carboxylic acid functional group in a protein is determined to be 5.0. This
carboxylic acid is thought to contribute a hydrogen bond to a receptor that binds the protein. At
pH 5.0, would this residue be able to act as a hydrogen bond donor? How would this be different
at pH 7.5?
The carboxylic acid group in the protein can exist in two forms, protonated and unprotonated.
Because the pKa of the acidic proton is 5.0, at pH 5.0 there would be equal concentrations of the
protonated form (AH, on the left), and the unprotonated form (A-, on the right). Only the AH
form can donate a hydrogen bond (through the -O-H group) so at pH 5.0 there would be
sufficient potential for a hydrogen bond donor.
At pH 7.5, the pH is over 1 pH unit above the pKa. The solution conditions are less acidic, there are fewer protons in solution, so the carboxylic acid group loses the proton and essentially all these molecules are in the unprotonated form (A-, on the right). Because it cannot donate a
hydrogen bond in the A- form, at pH 7.5 this group cannot count as a hydrogen bond donor in
calculating the binding affinity between the protein and its receptor.
Antagonist
Binds to the same target, its response is different from a cognate substance
Agonist
Binds to the same target, but elicits a similar response to a cognate substance
Equation for calculating the concentration of the free (unbound) receptor
Keq = [RH]/[R]*[H]
If given Keq but need R simply do [R] = [RH]/Keq * [H]
Equation for calculating the total concentration of the receptor
[R]total = [R]free + [RH]
Equation for calculating the fraction of the receptors that are bound by the hormone
[RH]/[R]total
Equation for calculating the fraction of the hormone that is bound by the receptors
[RH]/[H]total. = [RH]/[RH] +[H]
In general, the interact of molecules (hormones, drugs) with their targets (receptors) are the result of non-covalent interactions, including?
- charge-charge (coulombic) interactions
- hydrogen bonds
- hydrophobic interactions
- Van der Waals interactions (dipole-dipole, induced dipole)
A < - > B
Keq = [B]/[A]
How to find the concentration of the free receptor when given Keq, Rtotal, and RH
Rtotal - RH
How to find the fee bound receptor when given R, Rtotal, RH, and Keq
[R] = Rtotal - RH
How to find the concentration of the free hormone when given Keq, RH, Rtotal, R
Keq = [RH]/[R]*[H]
How to find the total concentration of the hormone when given RH, Rtotal, R, and Keq
[H]total = [H] + [RH]
How to find the fraction of the bound hormone when given Keq, Rtotal, R, RH, Htotal
RH = [RH]/[H]total
RH is what
H is what
R is what
The bound receptor
The free hormone
The free receptor
A < - > B
Keq = [B]/[A]
If Keq > 1, then what is favored?
If Keq < 1, then what is favored?
If Keq > 1, then the concentration of the product B is favored
If Keq < 1, then the concentration of the reactant A is favored
If Keq = 1 however, then neither the reactant or the product is favored
