Lect 1 Fundamentals Biochemical Reactions

Question 1

Metabolism is a _

Answer 1

• Series of Biochemical reactions

Question 2

Metabolism’s purpose is to _

Answer 2

• capture/harness energy from nutrients to sustain life

Question 3

Metabolism’s goals are _

Answer 3

Produce energy (catabolism)

Synthesize biomolecules (anabolism)

Question 4

Exergonic/Endergonic Definitions

Answer 4

Exergonic releases energy (deltaG < 0)

Endergonic consumes energy (deltaG > 0)

Question 5

Free Energy Change (delta G) = _

What is the Free Energy Equation?

Answer 5

delta G = Dynamics of biochemical reaction

deltaG = deltaG^o’ + RT ln [C][D]/[A][B]

Question 6

K_eq is equal to the ratio of the _

Answer 6

Products over Reactants

[C][D] / [A][B]

Question 7

Equilibrium Constant (K_eq) & Standard Free Energy (deltaG^o’) relationships

Answer 7

delta G is directly related to K_eq

K_eq = 1 –> deltaG^o’ = 0

K_eq > 1 –> deltaG^o’ < 0

K_eq < 1 –> deltaG^o’ > 0

Question 8

What are the kcal/mol values of:

ATP –> ADP + Pi

ATP –> AMP + PPi

PPi –> Pi + Pi

Answer 8

ATP –> ADP + Pi = -7.3 kcal/mol

ATP –> AMP + PPi = -10.9 kcal/mol

PPi –> Pi + Pi = -4.0 kcal/mol

Question 9

Mass Action (Le Chatelier)

Answer 9

• K_eq dependent on [R] and [P]
• Altering [R] or [P] alters reaction kinetics

Question 10

Input of Energy (Couple Reactions)

Answer 10

Endergonic + Exergonic

Must share a common intermediate

Final deltaG^o’ determines reaction fate

Question 11

Addition/Elimination Rxn

Answer 11

Transfer atom to multiple bond or elimination of atom to form double bond

Question 12

Substitution Rxn

Answer 12

Replace functional group with another

Question 13

Rearrangements (Isomerizations)

Answer 13

Shifting functional group within a molecule

Question 14

Oxidation-Reduction Rxn

Answer 14

Transfer of e- from one molecule to another

Question 15

Acid Base Rxn

Answer 15

Donating protons (acids) and accepting protons (bases)

Most important to preserve life

Question 16

Physiological pH Range

Answer 16

7.37-7.43

Question 17

What is the dissociation constant (K)

What is pKa an indicator of

Answer 17

Equilibrium constant indicating tendency of acid to dissociate

Acid strength (low pKa = strong acid)

Question 18

How does the Kidney regulate blood pH

Answer 18

Remove H+ in form of NH₄⁺ and reabsorb HCO₃^-

Low pH: increased H+ removal and HCO₃^- reabsorption

High pH –> less H+ removal and HCO₃^- reabsorption

Question 19

Name the Disorders Associated with Acid-Base Imbalances

Answer 19

Respiratory Acidosis (Hypoventilation)

Respiratory Alkalosis (Hyperventilation

Metabolic Acidosis

Metabolic Alkalosis

Question 20

Enzymes are biological _ that _ reaction rates

They bind to _ and convert them to _

Answer 20

Catalysts

Increase

Substrates to Products

Question 21

Enzymes increase reaction rate by _

Answer 21

• Lowering activation energy (E_A)
  
  • Minimum amount of energy to convert S to intermediate
• Stabilizing transition state intermediate
• Provide more energetically favorable reaction pathway

Question 22

Name the Enzyme Classes

Answer 22

Oxidoreductases

Transferases

Isomerases

Lyases (Synthases) - add/remove atoms to form double bond

Ligases (Synthetases) - form bonds with ATP hydrolysis

Hydrolases - cleave bonds via addition of water

Question 23

Enzymes made up of _ and folded into _ and _ structure

Answer 23

• Polypeptides
• Folded into tertiary and quaternary structure

Question 24

What is the purpose of the Active Site

Answer 24

• Substrate binding location

Question 25

Lock and Key Hypothesis

Answer 25

Substrate is perfect fit for active site

Question 26

Induced Fit Hypothesis

Answer 26

Binding induces conformation changes in active site

Question 27

What are Cofactors? How do they interact with enzyme?

Answer 27

Metal ions, Essential trace elements Interact with enzyme via **noncovalent interaction and stabilize active site**

Question 28

Common Cofactor Examples and their Enzymes

Answer 28

**Cu:** Cytochrome C Oxidase **Fe:** Heme proteins **Mg:** ATPases **Se:** Glutathione peroxidase (antioxidant) - detoxify H₂O₂ **Zn**: Carbonic Anhydrase

Question 29

What are Coenzymes?

Answer 29

Small organic molecules dervied from vitamins

Question 30

Difference between Co-Substrate and Prosthetic Groups

Answer 30

* **Co-Substrate: Temporary Association** (bind then detach in altered state) * **Prosthetic: Permanent Association** (FAD, FMN, Heme)

Question 31

What Factors Affect Enzyme Activity?

Answer 31

* **Temperature: 37^oC** * ​Rate doubles every 10^oC until optimal temperature * Heat induced denaturation * **pH: between 4-8** * Exception: gastric enzymes (Pepsin) * **Covalent Modification** * Phosphorylation/Dephosphorylation

Question 32

What is the proton pump and where is it located? Why would PPIs be prescribed?

Answer 32

* Proton Pump = **H⁺/K⁺ ATPase** * **Parietal cells** lining gastric lumen * Pumps H⁺ into lumen --\> Combines with Cl^- to form **HC** * Indigestion, heartburn, ulcers require decrease gastric acid * **PPIs** prescribed (Omeprazole, lansoprazole) * **Reduce HCl production**

Question 33

What is Hypochlorhydria?

Answer 33

* Lower HCl production --\> Reduce nutrient absorption, increase food poison sensitivity, **reduce gastric enzyme efficiency** (pepsin, gastric amylase, gastric lipase)

Question 34

Enzyme Kinetics describes what? What 3 things is it dependent on?

Answer 34

* **Rate** of enzyme-catalyzed reaction * Dependent on: * Initial **Substrate [S]** * Enzyme-Substrate **affinity (K_m)** * Reaction **velocity (v, V_max)**

Question 35

What are the Michaelis Menten and Lineweaver Burk Equations?

Answer 35

Know the MM equation

Question 36

Describe the Michaelis-Menten and Lineweaver Burk Plots What do the x and y intercepts and slope mean on LB Plots?

Answer 36

x-int = -1 / K_m y-int = 1 / V_max slope = K_m / V_max

Question 37

How does Competitive Inhibition work? Effects on V_max and K_m? Can it be overcome? Describe the inhibition on the graphs

Answer 37

* Compete with substrate binding * No effect on V_max * K_m increased * If [I] is fixed, then increasing [S] allows substrate to outcompete inhibitor

Question 38

How does Noncompetitive Inhibition work? Effects on V_max and K_m? Can it be overcome? Describe inhibition on graphs

Answer 38

* Binds to E and to ES complex * Decrease in V_max * K_m unaffected * Inhibitor effects **cannot** be overcome by increasing substrate concentration

Question 39

How does Uncompetitive Inhibition work? Effects on V_max and K_m? Describe inhibition on graphs

Answer 39

* Only binds to ES complex * Decrease in V_max and K_m by same factor

Question 40

What are Metalloenzymes? How does chelation affect the enzymes?

Answer 40

* Enzymes requiring metal ions as cofactors (Mg, Zn) * Chelating of cofactors will inhibit enzyme activity * Chelating agent: Ethylene Diamine Tetraacetic Acid (EDTA)

Question 41

Why is Lead (Pb) toxic? Heme is a coenzyme of \_ Pb poisoning Sx include \_ Tx with _ and why does it work?

Answer 41

* Inhibits 2 enzymes in heme biosynthesis * **Heme is coenzyme of hemoglobin** * Sx: abdominal pain, sideroblastic anemia, irritability, HA, signs of impaired nervous system development and encephalopathy * Tx: Ca-EDTA with dimercoprol * Pb (higher affinity for EDTA) displaces Ca to form Pb-EDTA (excreted)

Question 42

Irreversible Inhibition caused by _ and what are examples of inhibitors? Effects on V_max and K_m? Can it be overcome?

Answer 42

* Destruction/Covalent Modification of functional groups of AAs in enzyme * Ex: Pb, Hg, organophosphates, cyanide, sulfide, aspirin * **Decrease V_max** and **K_m unchanged** * Only overcome by new E synthesis

Question 43

How do Allosteric Enzymes work?

Answer 43

* Activity modulated by **noncovalent binding** of **metabolite** to **site other than** the **catalytic site** * Affects S binding by **inducing conformational changes** * Effectors: **positive (activators, lower K_m) or negative (inhibitors, raise K_m)** * Feedback Inhibition

Question 44

What are Isozymes?

Answer 44

* Enzymes with the **s****ame catalytic function, different primary sequence** * Different biophysical properties

Question 45

Isozymes that are Markers of MI and how are they detected?

Answer 45

Creatine Kinase (CK-MB) Aspartate Aminotransferase (AST) LDH-1 **Blood serum levels increase after MI**

Question 46

Troponin in MI

Answer 46

* Troponin is Trimeric * **Troponin cTn-I (cardiac muscle) used as biomarker for detection of MI**

Question 47

What are Proenzymes (Zymogen)? How do they become active?

Answer 47

**Inactive precursor of enzyme** Need **proteolytic breakdown** to be active via cleavage of specific peptide bond