PHARM 701 Exam 1

What are the major biochemicals

1. Nucleic acid polymers

2. Proteins

3. Lipids

4. Carbohydrates

Define Nucleic acid polymers & key roles

Long polymers of nucleotides (DNA & RNA) with sugar-phosphate backbones. Store & transmit genetic information, RNA also participates in protein synthesis & regulation

Define Protein & key roles

Chains of amino acids (residues) linked by peptide bonds. Perform structural roles, catalyze biochemical reactions (enzymes), regulate processes (hormones), & act as receptors

Define Lipids & key roles

Hydrophobic or amphipilic molecules such as fats, sterols, phospholipids, glycerides, waxes, & fat-soluble vitamins. Provide energy storage, structural components of membranes, and signaling molecules

Carbohydrates function

Monosaccharides & polysaccharides linked by glycosidic bonds. Serve as energy sources, structural components, and cell recognition molecules.

What are the common biochemical elements

1. Carbon

2. Hydrogen

3. Nitrogen

4. Oxygen

5. Phosphorus

6. Sulfur

(CHNOPS)

What are the functional groups important to bioactivity of biological molecules?

1. Hydrocarbons (aliphatic & aromatic)

2. Hydroxyl (-OH)

3. Carbonyl (C=O)

4. Carboxyl (-COOH)

5. Amino (-NH2)

6. Sulfhydryl (-SH)

7. Phosphate (-PO4)

Why are functional groups important?

Influences solubility, reactivity, & interactions with biological molecules. Polar or charged groups enhance water solubility and hydrophobic groups promote membrane association

What are the building blocks of nucleic acids?

Nucleotides (Nucleoside + phosphate group_=)

What are the building blocks of Lipids?

Fatty acids, glycerol, steroids, Sphingosine

What are the building blocks for Proteins?

Amino acids

What are the building blocks for polysaccharides

Monosaccharides (simple sugars)

Why is steroid hormone a lipid?

Classified as a lipid because it is derived from cholesterol, hydrophobic, & has a characteristic fused 4-ring structure

Difference between insulin and steroid

Insulin is a protein (polypeptide) hormone composed of amino acids and is water-soluble. Steroid hormones are lipid-soluble and act via intracellular receptors

What is a special characteristic of numbering the carbons in the ribose sugar of a nucleic acid?

Ribose carbons are numbered with a prime symbol to distinguish them from the numbering in a nitrogenous base

How to know is a sugar is deoxyribose or ribose?

2' OH is ribose & 2' H is deoxyribose

How many nitrogen atoms are present in the base structure of purine

4 N atoms (2 rings)

How many nitrogen atoms are present in the base structure of pyrimidine?

2 N atoms (1 ring)

How do amino acids function as the building blocks of proeins

Proteins are polymers of amino acids linked by peptide bonds. The sequence of amino acids dictates the folding and function of the protein.

Cellular functions of amino acids and how they contribute to many aspects of the biochemistry of cells

- Forms proteins

- Are precursors for NTs, hormones, nucleotides, and other biomolecules

How does the nature of the side chain (polar, charged, aliphatic, etc) of an amino acid contributes to the functionality of the amino acid and/or the structure of a protein.

1. Nonpolar aliphatic = Hydrophobic interactions in protein cores

2. Aromatic = Stacking interactions & absorb UV light

3. Polar Uncharged = Hydrogen bonding

4. Charged = Ionic bonds, salt bridges, pH-depend interactions

5. Sulfur-containing = Disulfide bond formation for structural stability

For a protein, describe the characteristics of amino acid functional groups that impact pKa.

1. Carboxyl group (pKa = 2-2.5)

2. Amino group (pKa = 9-10) always present

3. Side chains with ionizable groups have additional pKa values affecting charge at physiological pH

A cirrhosis patient has mental status changes from high ammonia. Which nutrient should be most restricted to reduce ammo

Proteins

Which key biochemical property distinguishes nucleic acids from lipids, proteins, and carbohydrates?

Sugar-phosphate backbone & nucleotide bases

What are the building blocks of nucleic acids, lipids, proteins, and polysaccharides

Nucleotides, fatty acids, amino acids, and monosaccharides

Which chemical functional groups on biomolecules are important for biochemical function and drug activity?

Hydroxyl, amino, carboxyl, phosphate

What is the role of chaperone proteins

Help proteins fold

Which characterisitc is most associated with gobular proteins

They have complex teritary sturctures and are generally solbule in H2O

How do enzymes act as catalysts in biochemical reactions

By lowering the activiation energy and speeding up reactions

What effect do enzymes have on the activation energy and transition state of a reaction

Lower activation energy and stabilize the transition state

What roles do amino acid residues, coenzymes, and metal ions play at an enzyme's active site?

They help substrate binding and catalysis

What do parmacogenomics study

How DNA & RNA sequences impact/affect drug action

How are amino acids linked together to form peptides and proteins

Peptide bonds

What is central dogma

DNA -> Transcription (Nucleic acid polymer) -> mRNA -> Translation -> Protein (Amino acid polymer)

Higher the Ka means...

Greater tendency to dissociate a proton

Stronger the acid means

- Higher tendency to donate a proton (H+)

- Larger Ka

- Smaller Pka

- Weaker Cb

Acid dominates when...

pH < PKa

Base dominantes when

pH > PKa

If the structure is protonated what is the PI at to pH

pH < PKa (pro) -> pH < PI

If the structure is unprotonated what is the PI at to pH

pH > PKa -> (unpro) pH > PI

What is the pH range for an effective buffer

Plus one or minus the pKa

Absorption, Distribution, & Excretion on ionized

- Less absorbant

- H2O soluble

- Can't move readily across membrane

- More readily excreted

Absorption, Distribution & Excretion on unionize

- More absorbant

- Lipid soluble

- More distributed

- Move across membrane more readily

- Trap/Bad excretion

If you want urine excretion because the acid/unionze is favored you need too...

Make/shift equilibrium to be more ionized/ make urine more basic which inc pH

What's Myoglobin's Relationship with O2

- Higher bonding affinity to O2

- Hyperbolic

- O2 Storage tank

What is Hemoglobin's (Hb) relationship with O2

- Cooperative binding where O2 affinity inc as more O2 molecules are bound

- Highest at R-state where most heme groups are occupied

- Sigmoidal

- Allosteric protein

What is the bohr effect

As pH lowers, CO2 increases which decreases Hb O2 affinity which promotes O2 release in active tissue

Diane has a low pH at 7.08 & a high [H+] with a serum HCO3- at (8 m Eq/mL) & PaCO2 at 28 mmHg. She has diabetic ketoacidosis. Why does her lab results make sense?

DKA givrtd her a condition where she is always in a fasting state/cells starve for energy. DKA makes a lot of ketone bodies specifically ketoacids where are weak acids that increase [H+] thus lowering her pH. HCO3- is used up to buffer the acids. The body tries to compenstate by breathing faster/increase respiratory rate to blow/expel the CO2 thust PaCO2 falls

Which of the following contions is most likely to slow down enzyme activity in your body without permanently denaturing to proteins

Cooling your body temp to 34 degrees C

Which statement about enzymes as catalysts is false?

Enzymes riase the energy of the transition state

A genetic defect results in an enzyme that cannot interact with its required activation-transfer coenzyme. Which of the following outcomes is most likely?

The enzyme catalytic activity will be significantly decreased or absent

What are the enzymre classifications

1. Oxidoreductases

2. Transferases

3. Hydrolases

4. Isomerases

5. Ligases

6. Lyases

Oxidoreductases

Transfer of electrons

Transferases

Group transfer reactions/ transfer functional group

Hydrolases

Hydrolysis reaction/transfer of functional groups to H2O

Ligases

Form bonds with ATP hydrolysis/ Formation of C-C, C-S, C-O, & C-N bonds

Lyases

Add/remove groups to/from double bonds

Catalytic strategies

1. General Acid-Base (accept/donate protons)

2. Covalent

3. Metal-Ion

4. Catalysis by approximation (Enzyme activr site forces substrate to bind in the active site placing reactive groups to fav a catalytic rxn)

5. Cofactor

Cofactor

Non-protein helper, either metal ion or organic molecule

Coenzyme

Organic cofactor often a vitamin

Reversible inhbition

Can be overcome/removed, the enzyme returns to normal function

Irreversible inhibition

Enzyme permanently inactivated

Suicide/Mechanism-based inhibitor

Act as a transition state analog to permanently inactive enzymes

Relationship of Km to enzyme affinity

- Inc Km = Dec enzyme affinity for substrate

- Dec Km = Inc enzyme affinity for substrate

Competitive inhbition

- Reverisible inhbitor

- Inhibitor competes with substrate at same acitvity site for binding

(A lot of drugs are competitive inhbitors)

What is competitive inhibitor effect on Km & Vmax

- Km increases; decrease affinity & more substrate needed

- Vmax does not change; can be overcome with enough substrate

- Michaelis-Menten curve shifts right

- Lineweaver-Burke plot lines intersect at y-axis

In a Lineweaver-Burke plot (1/V= Km/Vmax(1/[S]) + 1/Vmax) which of the following does the y-intercept correspond to

1/Vmax

Noncomeptitive inhbition

- Inhbitor does not compete

- Inhibitor that binds to allosteric site (E or ES Complex), changes enzyme conformation

- An inc in concentration will NOT overcome inhibition

Noncompeitive inhibtion affect on Km & Vmax

- No change to Km, substrate binding not directly affected

- Dec Vmax, enzyme max cap reduced and can't be fixed by adding substrate

- Michaelis-Menten curve lower plateau

- Lineweaver-Burk plot lines do not cross at y

Allosteric Regulation

- Small molecules bind to non-active sitre

- Can activate or inhbit enzymes

- Often in metabolic pathways

Covalent/Phosporylation modification

- Reversible & Irreversible

- Fasty way to turn enzymes on/off without changing their synthesis rate

protein-protein interactions

- Binding of regulatory proteins to enzymes alters activity

What is a salt bridge

Interaction between a positive side chain of one amino acid and a negative chain side of another amino acid