Biochemistry II

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Biochemistry II

• Test 2 Review

2
The Big Picture

• All systems do not stand alone and are
  interrelated.
• As we study each system, look at how that system
  may affect others.
• Anything that stimulates/inhibits a system also
  stimulates/inhibits every enzyme in that pathway.

3
Back to the Future

• Remember the pathways from unit one?!
• ATP-PC
• Glycolysis
• Krebs Cycle
• ETS

4
Phosphagen System
5
Phosphagen System

• Location Cytosol
• Key enzyme Creatine Kinase
• Fastest rate of ATP production
• Makes one ATP per cycle

6
Glycolysis
7
Glycolysis

• Location
• Cytosol
• Purpose
• Make ATP
• Make precursors to the aerobic system
• Key enzymes
• Hexokinase
• PFK
• Pyruvate Kinase

8
Glycolysis

• PFK
• The rate limiting enzyme of Glycolysis.
• Why not Hexokinase?
• THE BIG PICTURE!

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Regulation of Glycolysis
10
Glycolysis

• What is the role of Lactate?
• How Why?
• Remember the BIG PICTURE!

11
Krebs Cycle
12
Krebs Cycle

• Location
• Mitochondria
• Puropse
• Harvest H and send it to the ETS
• The preparation step
• Pyruvate Dehydrogenase

13
TCA

• Key Enzymes
• Citrate Synthase
• Isocitrate Dehydrogenase
• Alphaketogluterate Dehydrogenase
• Malate Dehydrogenase

14
Citric Acid Cycle
15
ETS
16
ETS

• Location
• Inner mitochondrial membrane
• Purpose
• ATP

17
Oxidative Phosphorylation
18
Pentose Phosphate Pathway
19
Pentose Phosphate Pathway

• Location Cytosol
• Purpose
• NOT ATP
• Generate Reducing Power
• Make Five-carbon sugars
• Glycolysis Remember Overlap

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Hexose Monophosphate Pathway

• NADPH
• Used in reductive biosynthesis to make fat and
  steroids.
• Detoxification.
• WBC activity.
• Free radical protection.
• Five Carbon Sugars
• Ribose.
• Used for many biological processes
• ATP, CoA, NAD, FAD, RNA, DNA.

21
Phosphogluconate Oxidative Pathway

• NADH v. NADPH
• NADH Important for ATP production.
• NADPH Important for reductive biosynthesis.

22
PPP and Glycolysis

• PPP/Glycolysis overlap
• Glucose-6-P
• Glyceraldehyde-3-P
• Fructose-6-P

23
PPP Reactions

• The first half of the PPP.
• Oxidative
• Makes NADPH
• Irreversible
• The second half of the PPP.
• Non-oxidative
• Reversible
• Produces Ribose
• The intermediates can re-enter Glycolysis.

24
Bodys Most Wanted

• Superoxide
• O2
• Hydrogen Peroxide
• H2O2
• Hydroxyl
• OH

25
Bad Boys, Bad Boys

• Superoxide Dismutase
• O2 H2O2
• Catalase
• H2O2 H20 O2
• Glutathione Peroxidase
• H2O2 H2O

Your Reacting Days Are Over!!
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PPP Regulation

• The regulation of the PPP is determined by
  metabolic need.

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Gluconeogenesis
28
Gluconeogenesis

• Location
• Liver (Cytosol)
• Purpose
• Make new glucose
• ATP
• Uses Six ATP
• Key Enzymes
• Pyruvate Carboxylase
• PEP Carboxykinase
• Fru-1,6-BisPhosphatase
• Glucose-6-Phosphatase

29
Gluconeogenesis

• Essentially, Gluconeogenesis is Glycolysis
  backward.
• Glycolysis Key Enzymes
• Hexokinase
• PFK
• Pyruvate Kinase
• BIG negative ?G.

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Gluconeogenesis

• Pyruvate
• The common starting point of GNG
• Cannot leave the cell
• How do we get it to the liver for GNG?
• Lactate (Cori Cycle)
• Alanine (Glucose-Alanine Cycle)

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Overview
34
Gluconeogenesis
35
Gluconeogenesis

• Final Notes
• Glucose can also be made from Glycerol in GNG,
  but that will be covered later.
• Acetyl CoA and compounds that make Acetyl CoA
  cannot be made into glucose.
• The role of the Malate shuttle in GNG.
• Pyruvate ? OAA
• OAA moved into the cytosol by the Malate shuttle.
• OAA ? PEP

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Glycogen
37
Glycogen

• Starch is a molecule that is made of
• many individual sugar molecules.
• Eg.
• Amylose
• Cellulose
• Amylopectin
• Glycogen

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Glycogen

• Many starches have a branching pattern.
• Glycogen Every 10 Glucose
• Amylopectin Every 30 Glucose
• This has several benefits.
• Increased water solubility.
• Many non-reducing ends.
• Increased rate of formation and degradation.

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Glycogen

• Location
• Stored in the cytosol.
• Muscle 400g
• Liver 100g
• Goal
• Store Glucose for
• later use.
• Common bonds
• ? 1?4 (chain)
• ? 1?6 (branch)
• Branches
• About every 10 glucoses

40
Glycogen Synthesis

• Initiation
• UDP Glucose is attached to Glycogenin by the
  enzyme Glycogen Initiator Synthase
• Elongation
• The addition of glucose to glycogen By the
  enzyme Glycogen Synthase
• Branching
• The formation of a side chain of glucose by the
  enzyme Glucosyl 46 Transferase

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Glycogen Degradation

• Glycogen Phosphorylase
• Cuts off individual glucoses up to four away from
  a branch.
• Glucosyl 44 Transferase
• Cuts off the outer three glucose
• Amylo-?-(1,6)-Glucosidase
• Cuts off the last glucose of the branch.
• Once the branch is removed Glycogen Phosphorylase
  takes over again, and the process continues.

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Glycogen Regulation
45
FA Metabolism
46
Fact and Function

• FA Fact
• Most often an even number of carbons.
• 16 and 18 are most common
• The properties of a FA are mostly determined by
• Length
• Saturation
• Double bonded carbons are predictably separated
  by a methylene group.

47
FA Construction

• Humans can make most of the FAs they need.
• Non-Essential FA
• But, some of them cannot be made by our body, so
  we must consume them.
• Essential FA
• Linoleic Acid 182w6
• Linolenic Acid 183w3
• Arachadonic Acid 204w6

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A Look at Structure
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A Look at Structure
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FA Shape

• Cis Trans

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FA Metabolism

• ? system Starts numbering at the last CH3
  carbon.
• nn?n

1
2
3
4
?
?
?
?
The distal carbon is the omega carbon
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FA Storage
53
FA Oxidation

• Location
• Mitochondria
• Purpose
• Make Acetyl CoA to send
• to the TCA
• ATP

54
FA Oxidation

• In order for fat to be broken down, it must be
  moved from the cytosol to the mitochondria.
• This is accomplished by
• Carnitine.

FA
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FA Oxidation

• Lipase
• Cuts FAs off of Glycerol, breaking down TAGs.
• AKA
• TAG Lipase
• Hormone Sensitive Lipase (HSL)

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FA Oxidation

• Oxidation
• Dehydrogenase
• Hydration
• Hydratase
• Oxidation
• Dehydrogenase
• Thiolysis
• Thiolase

57
FA Breakdown

• Unsaturated FAs require two extra steps.
• Reductase
• Isomerase
• Odd numbered FAs end their breakdown as Propionyl
  CoA that is changed to Succinyl CoA and sent to
  the Krebs Cycle.

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Regulation of Lipolysis
59
FA Synthesis

• Location
• Cytosol
• Purpose
• Store energy

60
FA Synthesis

• FAs are built by adding two carbons at a time.
• Acetyl CoA
• Converted to citrate to leave the mitochondria
• Citrate is changed back to Acetyl CoA once in the
  cytosol

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FA Synthesis

• Preparation Step
• The coenzyme for this reaction is biotin.

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Lipogenesis

• Condensation
• Fatty Acid Synthase
• Reduction
• Fatty Acid Synthase
• Dehydration
• Fatty Acid Synthase
• Reduction
• Fatty Acid Synthase
• This process will continue over and over until
  the FA is 16 carbons long.

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Regulation

• Stimulation
• High EC
• NADPH
• NADH/FADH2
• Citrate
• Insulin

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Regulation of Lipogenesis

• Inhibition
• ADP
• NADP
• NAD/FAD
• Palmitoyl CoA
• Norepinephrine
• Epinephrine
• Glucagon
• Cortisol
• ACTH
• Malonyl CoA (only inhibits Acetyl CoA
  Carboxylase)

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Q A
66

• What pathways are typically stimulated by low
  ATP?
• What pathways are typically stimulated by high
  EC?

67

• What is a product of PPP?
• NADH
• NADPH
• Glucose
• Acetyl CoA

68

• What is NADPH used for?
• Carrying H to the ETS
• Changing pyruvate to lactate
• Making fat
• Making sugar

69

• What is ribose used in?
• NAD
• Glycogen
• Succinate
• CoQ

70

• How many NADPH are made from a glucose?
• 0
• 2
• 4
• 8

71

• How many ATP are produced by the PPP?
• 0
• 1
• 2
• 30

72

• How many ATP are used by the PPP?
• 0
• 5
• 10
• 30

73

• What does the oxidative part of PPP make?
• NADH
• FADH2
• NADPH
• FADPH2

74

• What does the reversible part of PPP make?
• Ribose
• Glucose
• Glycogen
• Fumerate

75

• What tissue/cell use PPP the most?
• Muscle
• Bone
• Liver
• Kidney

76

• What is the key enzyme of PPP?
• Hexokinase
• Glucose-6-P Dehydrogenase
• PFK
• Glucose-6-Phosphatase

77

• Where does PPP take place?
• Cytosol
• Mitochondria
• Cell membrane
• Endoplasmic reticulum

78

• Where does GNG take place?
• Cytosol
• Mitochondria
• Golgi Apparatus
• Muscle spindle

79

• Which of these nutrients is not gluconeogenic?
• Carbohydrates
• Protein
• Fat
• Amino acids

80

• Which of the following cannot enter GNG?
• Glycerol
• Alanine
• Acetyl CoA
• Pyruvate

81

• What cycle uses lactate to get pyruvate to the
  liver?
• Cori cycle
• Glucose-Alanine cycle
• Citric acid cycle
• Oxdative phosphorylation

82

• What cycle uses Alanine to get pyruvate to the
  liver?
• Cori cycle
• Glucose-Alanine cycle
• Citric acid cycle
• Oxdative phosphorylation

83

• What three things can be used as reactants in
  GNG?
• Pyruvate
• AA
• Glycerol

84

• Under what conditions does muscle use the most
  glucose for energy?
• Long duration
• High intesity
• Low intesity
• Rest

85

• Why does GNG use different enzymes than
  glycolysis?

86

• How many ATP are used to remake glucose in GNG?
• 0
• 3
• 6
• 12

87

• What are the key enzymes of GNG, and what
  glycolytic enzymes reverse them?

88

• What role does OAA have in GNG?

89

• Why is Acetyl CoA not gluconeogenic?
• It is not water soluble
• It is not energetically favorable
• It cannot leave the mitochondria
• The molecule is too big

90

• Where do ketones come from?
• OAA
• Succinyl CoA
• Acetyl CoA
• Malonyl CoA

91

• What hormone stimulates GNG?
• Insulin
• Glucagon
• Norepinephrine
• Cortisol

92

• Which of the following is a powerful 2nd
  messenger?
• Cyclic ATP
• Cyclic AMP
• Cyclic ADP
• Cyclic GMP

93

• What type of bond makes up the branch in
  glycogen?
• a 1,4
• a 1,6
• ß 1,4
• ß 1,6

94

• Where is glycogen stored?
• Cytosol
• Mitochondria
• Endopalsmic reticulum
• Golgi apparatus

95

• Where is glycogen made?
• Cytosol
• Mitochondria
• Endopalsmic reticulum
• Golgi apparatus

96

• Where is glycogen broken down?
• Cytosol
• Mitochondria
• Endopalsmic reticulum
• Golgi apparatus

97

• What is not a key enzyme of glycogen synthesis?
• Glycogen Synthase
• Glucosyl 44 Transferase
• Glucosyl 46 Transferase
• Glycogen Initiator Synthase

98

• What is not a key enzyme of glycogen breakdown?
• Glycogen Phosphorylase
• Glucosyl 44 Trasferase
• Glucosyl 46 Transferase
• Amylo-?-(1,6)-Glucosidase

99

• How much glycogen is stored in the muscle?
• 100g
• 200g
• 400g
• 800g

100

• How much glycogen is stored in the liver?
• 100g
• 200g
• 400g
• 800g

101

• What is the job of glycogenin?

102

• What enzyme builds the chain of glycogen?
• Glycogen Synthase
• Glucosyl 44 Transferase
• Glucosyl 46 Transferase
• Glycogen Initiator Synthase

103

• What enzyme builds the branch of glycogen?
• Glycogen Synthase
• Glucosyl 44 Transferase
• Glucosyl 46 Transferase
• Glycogen Initiator Synthase

104

• What enzyme breaks down the chain of glycogen?
• Glycogen Phosphorylase
• Glucosyl 44 Trasferase
• Glucosyl 46 Transferase
• Amylo-?-(1,6)-Glucosidase

105

• What enzyme breaks the a 1,6 branch of glycogen?
• Glycogen Phosphorylase
• Glucosyl 44 Trasferase
• Glucosyl 46 Transferase
• Amylo-?-(1,6)-Glucosidase

106

• What enzyme cuts off the outer 3 glucoses in a
  branch of glycogen?
• Glycogen Phosphorylase
• Glucosyl 44 Trasferase
• Glucosyl 46 Transferase
• Amylo-?-(1,6)-Glucosidase

107

• How often does glycogen branch?
• No branches
• Every 10 glucose
• Every 30 glucose
• Every 50 glucose

108

• How often does amylopectin branch?
• No branches
• Every 10 glucose
• Every 30 glucose
• Every 50 glucose

109

• How often does amylose branch?
• No branches
• Every 10 glucose
• Every 30 glucose
• Every 50 glucose

110

• What sugar makes up amylose?
• Lactose
• Glucose
• Maltose
• Fructose

111

• What sugar makes up maltose?
• Glucose
• Fructose
• Ribose
• Galactose

112

• What sugar makes up amylopectin?
• Glucose
• Fructose
• Ribose
• Galactose

113

• Hexokinase?

114

• What is not a benefit of branching in glycogen?
• Increased solubility
• Increased rate of utilization
• Decreased rate of storage
• Increased number of non-reducing ends

115

• Why is fat preferred for energy storage?

116

• Know the structures of fats.

117

• A FA 182w6 has how many double bonds?
• 0
• 1
• 2
• 3

118

• Which is a saturated FA?
• 160
• 182w6
• 183w3
• 162w3

119

• What are some of the characteristics of an
  unsaturated FA?
• Cis
• Trans
• Methlyene interuption

120

• What is the major benefit of a FA being highly
  reduced?
• Decreased solubility
• Increased H
• Less methylene
• More double bonds

121

• Where are FA broken down?
• Cytosol
• Mitochondria
• Nucleus
• Ribosome

122

• Where are FA made?
• Cytosol
• Mitochondria
• Nucleus
• Ribosome

123

• Where are FA stored?
• Cytosol
• Mitochondria
• Endopalsmic reticulum
• Golgi apparatus

124

• What always separates multiple double bonds in a
  FA?
• CO2
• CH2
• NO3
• CH3

125

• Which is an essential FA?
• Butyric acid
• Linoleic acid
• Laurate
• Oleate

126

• Know the reaction sequences of FA metabolism.
• Synthesis
• Degradation

127

• What is an enzyme of FA synthesis?
• Dehydrogenase
• Hydratase
• Acetyl CoA carboxylase
• Thiolase

128

• What is not an enzyme of FA oxidation?
• HSL
• Dehydrogenase
• Acetyl CoA carboxlyase
• Hydratase

129

• If you have lots of energy, the metabolic trend
  will be toward ___________.
• Synthesis
• Degradation

130

• Which would increase the amount of the enzyme
  Acetyl CoA Carboxylase?
• High carbohydrate, low fat diet
• Low carbohydrate, high fat diet

131

• What enzyme is responsible for building FA?
• FA synthase
• Acetyl CoA Carboxylase
• Amylo-?-(1,6)-Glucosidase
• FA dehydrogenase

132

• What is the most common length of FA in humans?
• 8
• 16
• 24
• 32

133

• What is the name of this FA 160?
• Aracadonate
• Palmitate
• Oleate
• Linoleate

134

• Which of the following is an w6 FA?
• Linolenate
• Palmitate
• Oleate
• Linoleate

135

• Which of the following is a w3 FA?
• Linolenic acid
• Palmitate
• Oleate
• Linoleate

136

• What enzyme forms Acetyl CoA in the cytosol?
• Pyruvate dehydrogenase
• Citrate lyase
• Acetyl CoA carboxykinase
• Thiolase

137

• Increased activity of what pathway would
  stimulate glucose-6-P dehydrogenase?
• Glycolysis
• FA synthesis
• TCA
• FA oxidation

138

• Which of the following would stimulate glycogen
  phosphorylase?
• Insulin
• ATP
• ADP
• NADH

139

• Glucagon would stimulate what pathway?
• Glycolysis
• PPP
• FA synthesis
• Glycogen degradation

140

• Increased activity of GNG would inhibit what
  pathway?
• Krebs
• Glucose-alanine
• Glycogen breakdown
• Cori cycle

141

• Which of the following would inhibit lipolysis?
• NAD
• Citrate
• FAD
• ADP

142

• Increased activity in the Krebs cycle would
  inhibit what pathway?
• Glycolysis
• PPP
• FA oxidation
• Glucose-Alanine cycle

143

• Increased utilization of carnitine would indicate
  increased activity of what pathway?
• PPP
• FA synthesis
• Cori Cycle
• Lipolysis

144

• Increased levels of insulin would stimulate which
  enzyme?
• Glycogen synthase
• Amylo-?-(1,6)-Glucosidase
• Glucosyl 44 Transferase
• HSL

145

• Norepinephrine would stimulate what enzyme?
• Hormone sensitive lipase
• Glycogen synthase
• PEP Carboxykinase
• Acetyl CoA Carboxylase

146

• If FA elongation is carried out as far as
  possible, what FA is made?
• Aracadonate
• Palmitic acid
• Oleate
• Linoleate

147

• Increased activity of Acetyl CoA carboxylase
  would stimulate what pathway?
• Glycolysis
• GNG
• ETS
• PPP

148

• Formation of nucleic acids would stimulate what
  enzyme?
• PFK
• Hexokinase
• Glucose-6-P Dehydrogenase
• Acetyl CoA carboxylase

149
Remember

• THE BIG PICTURE!
• AND
• If youve never seen it, dont pick it.