Lecture 1: Fundamentals Of Biochemical Reactions (Zaidi) Flashcards Preview

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Flashcards in Lecture 1: Fundamentals Of Biochemical Reactions (Zaidi) Deck (98):
1

LO 1. Recall the principles of biochemical reactions
(A) Identify what free energy change (delta G) indicates:

Indicates spontaneity of a reaction and amount of “useful” energy the reaction can produce to do work

Delta G= Delta G(standard conditions)’+RTln [C][D]/[A][B]

2

LO 1. Recall the principles of biochemical reactions

DeltaG=DeltaG at standard conditions +RTln [C][D]/[A][B]

Explain what is occurring when:
Delta G=0, Delta G<0, Delta G>0

Delta G=0; equilibrium

Delta G<0; spontaneous/exergonic

Delta G>0; non-spontaneous/endergonic

3

LO 1. Recall the principles of biochemical reactions

DeltaG(standard conditions)=-RTlnKeq

Describe what is occurring when:
Keq=1, Keq>1, Keq<1

Keq=1, equilibrium

Keq>1, DeltaG(at standard conditions)<0, reaction spontaneous

Keq<1, Delta G (at standard conditions)>0, reaction non-spontaneous

4

What is the purpose of metabolism?

Capture/harness energy from nutrients

5

What are the goals of Metabolism?

1. Produce energy using catabolic pathways
2. Synthesize biomolecules using anabolic pathways

6

What are the two types of biochemical reactions?

1. Exergonic
2. Endergonic

7

What does DeltaG measure?

The spontaneity of a reaction

8

What does negative delta G represent?

Spontaneous/exergonic reaction

9

What does a positive delta G represent?

Non-spontaneous/endergonic reaction

10

Describe Mass Action:

(aka Le Chatelier's principle)
-Keq dependent on concentration of [R] and [P]
-Altering [R] or [P] can alter reaction kinetics
-If reaction is to the left (i.e. Keq<1), it can be pushed to the right
-By increasing reactants, decrease products

11

Describe Input of energy (coupled reactions):

-Endergonic reaction coupled to exergonic reaction to make the former happen
-Must share a common intermediate
-ATP powers biochemical reactions (hydrolysis is highly exergonic)

12

Name an example of mass action

First 3 steps in glycolysis; coupled and irreversible reactions

13

What are the 5 major types of reactions?

1. Addition/Elimination
2. Substitution
3. Rearrangements
4. Oxidation-Reduction
5. Acid-Base

14

What is an Addition/Elimination reaction?

Transfer of an atom to a multiple bond or elimination of an atom to form multiple bond

15

What is a Substitution reaction?

Replacement of a functional group with another

16

What is a Rearrangement reaction?

Shifting of a functional group within a molecule

17

What is Oxidation-Reduction reaction?

Transfer of an election from one molecule to another

18

What is an Acid-Base reaction?

Involve molecules that donate protons (acids) and accept protons (bases)

***most important to preserve life

19

What is the body's buffering system?

pH=7.37-7.43

20

What is Acetic Acid's chemical formula?

CH3COOH

21

What is Acetate's chemical formula?

CH3COO-

22

What is Bicarbonate's chemical formula?

HCO3-

23

What is Carbonic Acid's chemical formula?

H2CO3

24

What does the dissociation constant (K) represent?

equilibrium constant, indicates the tendency of an acid to dissociate

25

What does pKa represent?

indicator of the strength of an acid

26

What does pH=pKa reveal?

Optimal buffering capacity of acid-conjugate base

27

CORRELATION BOX: Acid-Base balance and kidneys: Describe the function of the kidneys

-Regulate blood pH
-Remove H+ from blood in the form of NH4+ and reabsorb HCO3-
-Low blood pH increases removal of H+ and reabsorption of HCO3-
-High pH results in fewer H+ removed and less reabsorption of HCO3-

28

What is the NORMAL BLOOD pH?

7.37-7.43

29

What leads to respiratory acidosis?

Hypoventilation!!!

Leads to increase in concentration of CO2 in blood

30

What leads to metabolic acidosis?

Addition of strong acid or loss of HCO3-

31

What leads to respiratory alkalosis?

Hyperventilation!!!

Leads to a decrease in the concentration of CO2 in the blood

32

What leads to metabolic alkalosis?

Addition of strong base, loss of acid (e.g. via vomiting)

33

Describe an enzyme:

-Biological catalysts
-Increase reaction rate
-Bind to substrates and convert them to products
-Do NOT get consumed during reaction

34

How do enzymes increase reaction rate?

-LOWER ACTIVATION ENERGY (Ea)

35

Go to slide 19: be able to label A, B and C

A=Activation energy (un-catalyzed), B=Activation energy (catalyzed)
C= Delta G
D= transition state

36

Describe Enzyme structure:

-Made of 1 or more polypeptides
-Folded into a tertiary and quaternary structure
-Folding creates a pocket (active site)
-Local site for reaction to occur
-Some enzymes have additions sites for other non-protein molecules, "cofactors' and "coenzymes"

37

What is the active site for enzymes?

-3D cleft or pocket
-Substrate binding location

38

Define: Lock and Key hypothesis

substrate is a perfect fit for active site

39

Define: Induced fit hypothesis

binding induces conformational changes in active site

40

What are cofactors/coenzymes?

-non substrates
-non protein

41

How do cofactors interact with enzymes?

-Noncovalently, stabilize active site

42

How do coenzymes interact with enzymes?

derived from vitamins

43

Coenzymes: What is temporary association?

Bind and then detach in altered state

ex: NAD+ loosely associated, leave in a cha

44

Coenzymes: What is temporary association?

Bind and then detach in altered state

ex: NAD+ loosely associated, leaves in changed form (NADH, reduced)

45

Coenzymes: What is a prosthetic attachment?

Permanent association

ex: FAD, FMN, Heme

46

What are the factors that affect enzyme activity?

-Temperature
-pH
-Covalent modification (phosphorylation, dephosphorylation

47

CORRELATION BOX: Gastric Protron Pump Inhibitors. Describe

-Proton pump affected (H+/K+ ATPase)
-Found in parietal cells lining gastric lumen
-Pumps H+ into lumen where it combines with Cl- to form HCL
-Conditions include: indigestion, heartburn, ulcers
-Proton Pump inhibitors are prescribed
-Reduce HCL production

48

Enzyme Inhibition: What are the three methods of enzyme inhibition?

1. Competitive
2. Non Competitive
3. Uncompetitive

49

Define Competitive inhibitor

Resemble substrate, compete with substrate binding, can be overcome by increasing concentration of substrate

50

Define Noncompetitive inhibitor

binds to E and ES; at site other than substrate binding site

51

Define Uncompetitive inhibitor

only binds to ES complex, site other than substrate binding site

52

Describe the effects of Competitive inhibition on LWBP

-NO EFFECT ON VMAX
-Increase in Km

53

Describe the effects of Noncompetitive inhibition on LWBP

-DECREASE in Vmax
-Unchanged Km
-Inhibitor effects cannot be overcome by increasing substate concentration

54

Describe the effects of Uncompetitive inhibition on LWBP

-DECREAE in Vmax and Km by same factor

55

CORRELATION BOX: Inhibition of Metalloenzymes (*requiremetal ions as a cofactor)

-Chelating of cofactors will inhibit enzyme activity
-Example of a chelating agent is EDTA
-Lead poisoning

56

Describe Enzyme inactivation

IRREVERSIBLE!!!
-Decrease in VMax, Unchanged Km

57

What is an Allosteric enzyme?

-Activity modulated by noncovalent binding of a metabolite to a site other than the catalytic site
-Affects substrate binding by inducing conformational changes

58

What are Isozymes?

-Same catalytic function, slightly different primary sequence
-Markers of myocardial infarction (MI)

59

CORRELATION BOX: Troponin in Myocardial Infarction

-Protein complex necessary for muscle contraction
-Ca2+ binding causes conformational change transmitted to tropomyosin, allowing myosin to bind to actin filaments -> leads to muscle contraction
-Troponin cTN-1 used as biomarker for detection of MI

60

What is a proenzyme/zymogen?

Inactive precursor of enzyme

61

Discuss the importance of phosphoric acid anhydride bonds and thioester bonds

ENERGY STORAGE

62

What is Keq dependent on?

Concentration of [R] and [P]

63

What is (K)?

Dissociation constant=equilibrium constant, indicates tendency of an acid to dissociate

64

CORRELATION BOX: Kidneys

Low blood pH ______ removal of H+ and reabsorption of HCO3-

Increases

65

CORRELATION BOX: Kidneys

High blood pH results in ______ H+ removed and less reabsorption of HCO3-

fewer

66

What is carbonic anhydrase?

Regulates the conversion from H2CO3 to CO2

67

Name an example of a cofactor

Metal ions

68

What are the 5 Metal Ions that are used as cofactors?

1. Cu
2. Fe
3. Mg
4. Se
5. Zn

69

What protein requires Cu for activity?

Cytochrome c oxidase:

Accepts electrons from cytochrome-c in the electron transport chain

70

What protein requires Fe for activity?

Heme proteins:

Require Fe2+ to bind O2

71

What protein requires Mg for activity?

ATPases: hydrolyze ATP to ADP and use the released energy to do mechanical work (i.e. ion transport)

72

What protein requires Se for activity?

Glutathione peroxidase (antioxidant)

detoxifies hydrogen peroxide

73

What protein requires Zn for activity?

Superoxide dismutase (antioxidant)

Binds the free radical of molecular oxygen

74

What cofactor does cytochrome c oxidase require for activity?

Cu

75

What cofactor do Heme proteins require for activity?

Fe

76

What cofactor do ATPases require for activity?

Mg

77

What cofactor does Glutathione peroxidase require?

Se

78

What cofactor does Superoxide dismutase require?

Zn

79

Coenzymes are derived from...

vitamins

80

What are considered covalent modifications of enzymes?

Phosphorylation and dephosphorylation

81

CORRELATION BOX: Gastric Proton Pump Inhibitors

What is the proton pump?

H+/K+ ATPase

82

CORRELATION BOX: Gastric Proton Pump Inhibitors

Where is the gastric proton pump found?

Parietal cells lining gastric lumen

83

CORRELATION BOX: Gastric Proton Pump Inhibitors

Describe the function of the H+/ATPase pump

Pumps H+ into lumen where it combines with Cl- to form HCL

84

CORRELATION BOX: Gastric Proton Pump Inhibitors

What are the symptoms associated with PP?

Indigestion, heartburn, ulcers

85

CORRELATION BOX: Gastric Proton Pump Inhibitors

What drugs are prescribed for issues with PP?

Omeprazole, Iansoprazole, esomeprazole

86

CORRELATION BOX: Gastric Proton Pump Inhibitors

What do PPI medications do?

Reduce HCl production

87

CORRELATION BOX: Inhibition of metalloenzymes

What inhibits metalloenzymes?

CHELATING of cofactors

88

CORRELATION BOX: Inhibition of metalloenzymes

What is an example of a chelating agent?

Ethylene diamine tetraacetic acid (EDTA)

89

CORRELATION BOX: Chelating agents for lead poisoning

symptoms of lead poisoning?

-Abdominal pain
-Sideroblastic anemia
-Irritability
-Headaches
-Neurological: signs of impaired nervous system development and encephalopathy

90

Enzyme inactivation:

resembles what other form of enzyme inhibition?

Noncompetitive

91

Define allosteric enzyme

Activity altered by noncovalent bonding of a metabolite to a site other than catalytic site

92

How do allosteric enzymes induce function?

Induces conformational changes

93

What are the markers for Myocardial Infarction?

-Creatine kinase (CK-MB)
-Aspartate Aminotransferase (AST)
-Troiponin (cTn-1)
-Isozyme of lactate dehydrogenase LDH-1

94

Proenzymes/zymogens:

How to they become active?

Proteolytic breakdown

95

What is the proenzyme of pepsin?

pepsinogen

96

What is the proenzyme of trypsin?

trypsinogen

97

What is the proenzyme of thrombin?

prothrombin

98

What is the proenzyme of chymotrypsin?

chymotrypsinogen