Glycolysis Flashcards
(200 cards)
1
Q
To lose one pound of weight, ones caloric intake should decrease by approximately how many calories?
1500
2000
2500
3000
3500
A
3500
2
Q
In order to maintain his/her current weight, hw many calories will a 70 kg sedentary individual require daily?
1550
1850
2150
2450
2750
A
2150
(70 x 24 x 1.3 = 2150)
3
Q
Under fasting conditions, which of the following is true?
Muscle glycolysis is inhibited
Liver glycolysis is inhibited
Muscle glycogen degradation is inhibited (it can be turned on
Liver glycogen degradation is inhibited
A
Liver glycolysis is inhibited (Muscle glycolysis won’t be inhibited under fasting conditions)
4
Q
Still under initial fasting conditions which statement is correct (initial fasting conditions)?
Muscle glycogen synthesis increases
Adipocyte fate content increases
Urea synthesis increases
Lactate utilization by RBC increases
A
Urea synthesis increases (AA are now used as energy source and their waste is in urea)
5
Q
What is diabetes?
Type 1?
Type 2?
A
6
Q
What are you looking for?
A
7
Q
A type 1 diabetic has just eaten, but forgot to take insulin. Which of the following will occur as a result?
Fatty acid degradation in the liver will increase
Glycogen degradation in the liver will decrease
Gluconeogenesis in the liver will continue
RBC’s will increase their oxidation of fatty acids
A
Gluconeogenesis in the liver will continue (In absence of insulin gluconeogenesis will continue. But glucose levels will actually continue to rise because insulin is required for glucose uptake by the muscle and the adipose tissue and liver still pumps out glucose via gluconeogenesis. Insulin is required to stimulate glycogen synthesis.)
(RBC’s have no mitochondria and therefore cannot oxidize FA)
(RBC’s have no mitochondria and therefore cannot oxidize FA)
8
Q
Overview of Glycolysis
A
Two pathways of Glycolysis — Anaerobic and Aerobic
In order to generate Triglyceride we need to go through glycolysis.
Excess glucose goes through glycogen biosynthesis.
9
Q
Glycolysis in Muscle vs. Liver
A
10
Q
What type of metabolism is used when sprinting
A
Sprinting — Anaerobic Metabolism
11
Q
Glucokinase is found…
A
Glucokinase — liver and pancreas.
12
Q
Hexokinase is found…
A
In every other tissue but the liver and the pancreas
13
Q
Glucose-1-Phosphate is Isomerized into…
A
Glucose 1 phosphate is isomerated into Glucose-6-P
14
Q
What is the first committed step in glycolysis?
A
Phosphofructokinase 1 (PFK1) — Irreversible. Committed Step. Regulated Step.
15
Q
How many ATP’s are used to get to the point of having two triose’s?
A
2 ATP
16
Q
How does NAD become NADH?
Is this oxidization or reduction?
A
NAD+ accepts two electrons and a proton to become NADH
17
Q
What is a mutase?
A
Whenever we move a phosphate from one functional group to another.
18
Q
What is the function of dehydration?
A
Dehydration creates very high energy bond — about twice the energy of a high energy bond in ATP — ATP is 7kcal/mol where as the enolated phosphate is about 14 kcal/mol (which is doubled).
19
Q
Which enzyme regenerates NAD so it can be reused?
A
Lactate Dehydrogenase regenerates NAD by converting NADH so it can be reused.
20
Q
The Hexokinase Reaction
A
21
Q
The Phosphohexose Isomerase Step
A
22
Q
The Phosphofructokinase-1 Reaction (PFK-1)
A
23
Q
Difference between Bisphosphate vs. Diphosphate
A
24
Q
The Aldolase Reaciton
A
25
The triose phosphate isomerase reaction most closely resembles which other reaction?
## Footnote
Glucose to G6P
G6P to F6P
F6P to F1,6BP
F1,6BP to G3P and Dhap
**G6P to F6P**
26
When a compound is oxidized, it:
Loses water
Loses electrons
Gains electrons
Gains water
Loses electrons
27
Generation of a High Energy Bond
28
What is NAD+
29
Pellagra
30
The phosphoglycerate kinase reaction
31
What makes a reaction freely reversible vs. Irreversible?
Energy in high energy bond in the reactants is the same energy level as ATP in the product so overall energy is the same on both sides of the reactions which makes it reversible.
32
Substrate Level Phosphorylation
Substrate Level Phosphorylation — In the absence of Oxygen
33
Oxidative Phosphorylation
Oxidative Phosphorylation — Requires Oxygen.
34
Phosphoglycerate Mutase Step
35
Formation of ATP by Pyruvate Kinase
36
What are the 3 Irreversible Steps of Glycolysis?
37
PFK-1
38
Inhibitors of PFK1
39
Activators of PFK-1
40
ATP's role in PFK-1
ATP = Key Inhibitor — Indicates high energy levels.
41
Where does glycolysis occur?
Glycolysis — Occurs in the Cytoplasm
42
Where is Citrate Made?
Citrate is made in the Mitochondria
43
Explain Citrate's Role in Glycolysis
When Energy levels are high in the Mitochondria citrate accumulates and leaves mitochondria. When it leaves and goes into the cytoplasm it tells Glycolysis to slow down because we have lots of energy.
44
What's AMP Role's in Glycolysis
AMP tells glycolysis to speed up
45
Storing Energy
Can’t store ATP because if we stored energy as ATP it would feedback inhibit ATP production. That’s why we store as creatine phosphate in muscle.
46
F-2,6-BisPhosphate's role in Glycolysis?
Fructose 2,6 Bisphosphate is a major activator of PFK-1 which activates glycolysis.
47
Where does F2,6BP come from?
48
What is velocity?
The rate at which the product of the reactoin is formed.
49
How does F-2,6-BP Effect the Activity Profile of
PFK-1?
F-2,6-BP reduces substrate concentration required for enzyme to reach 1/2 maximal velocity.
The Maximum velocity does not change but the amount of substrate required to reach that velocity is decreased.
50
Which curve is more active and which is more inhibited?
More active curve is to the left — enzyme is active at lower substrate concentrations.
More inhibited curve to the right
51
What are ATP's two roles with PFK-1?
ATP has two roles in this enzyme — at low ATP conc. it allows it to proceed because its a substrate. But as we increase the ATP it starts to be an inhibitor. That’s why we see the curve go up then down.
Mixed allosteric function. First as a substrate then once too it becomes too much it becomes inhibited.
52
The glycolytic rate can be increased by which one of the following?
## Footnote
Increasing G6P levels
Increasing ATP levels
Increasing citrate levels
Increasing pyruvate levels
Increasing NAD+ levels
**Increasing G6P levels (We increase g6p we’ll make more F6P which will increase substrate and increase the rate)**
Increasing NAD+ levels — won’t allow glycolysis to increase rate unless we also increase the substrate in that specific enzyme.
53
A key difference between liver and muscle glycolysis is which one of the following?
F2,6 bp is not Important in muscle
Lactate formation Is exclusive to liver
Glucokinase vx. Hexokinase
Amp only actives in muscle
Muscle will not slow down glycolysis in presence of ATP
Lactate formation Is exclusive to liver
54
What hormone is released when blood glucose levels drop?
## Footnote
Insulin
Glucagon
Vitamin D
Acetylcholine
Glucagon
55
Hormonal Regulation of PFK-2 in Liver
R is regulatory subunit
C is catalytic subunit
56
Why don't muscle cells respond to low blood sugar?
Muscle cells do not have glucagon receptors. Muscle cells don’t respond to low blood glucose.
57
When PFK2 is NOT phosphorylated
When PFK2 is not phosphorylated it acts as a kinase
58
When PFK2 is phosphorylated...
When PFK2 is phosphorylated it acts as a phosphatase
59
By phosphorylating PFK2
By phosphorylating PFK2 we are destroying F 2,6 BP.
60
Skeletal Muscle Isozyme of PFK-2...
Skeletal Muscle Isozyme of PFK2 never gets phosphorylated. PFK2 in skeletal muscle is only regulated allosterically.
61
More on PFK-2
62
Skeletal muscle does have protein kinase A but...
Skeletal muscle does have protein kinase A but it does not phosphorylate PFK2 because in the skeletal muscle it’s not a substrate for that enzyme.
63
PFK-2 Regulation in the Liver vs. Muscle
64
Heart PFK-2
65
Regulation of Hexokinase vs. Glucokinase
66
G6P's effect on Glucokinase vs. Hexokinase
G6p is an allosteric inhibitor of Hexokinase. G6p is not however a regulator of Glucokinase.
67
3 Forms of Pyruvate Kinase
68
L-Form of Pyruvate Kinase
69
M-Form of Pyruvate Kinase
70
Explain the Role of cAMP dependent protein kinase in the liver
71
Which one of these correctly describes the activity state of key glycolytic enzymes if you go for a run after waking up without eating breakfast.
## Footnote
Muscle and liver pfk1 are active
Only liver pfk1 is active
Muscle and liver pfk2 are active (kinase activity)
Only liver Pfk2 is active (kinase activity)
Only muscle PFK-1 and PFK2 kinase activities are active
**Only muscle PFK-1 and PFK2 kinase activities are active**
Muscle and liver pfk2 are active (kinase activity) — no in the liver its the phosphatase activity
Only liver Pfk2 is active (kinase activity) — no again it’s phosphatase activity is active
72
Allosteric Regulation vs. Covalent Modification
73
Regulation of Liver vs. Skeletal Muscle
74
Where does the liver get its energy for its own function when blood glucose is low?
Liver gets its own energy from the Fatty Acids which are released when glucagon is present.
75
Arsenic poisoning is due to the presence of arsenate and arsenite in the toxin arsenal was as a phosphate analog but arseon-anhydride bonds are unstable and rapidly hydrolyzed in water which glycolytic enzyme catalyzers a reaction that would be most affected by the presence of arsenate:
## Footnote
Glucokinase
PFK -1
PFK-2
Glyceraldehyde 3-phosphate dehydrogenase
Pyruvate Kinase
Lactate dehydrogenase
Glyceraldehyde 3-phosphate dehydrogenase (only enzyme that uses a free inorganic phosphate so it will be affected)
76
Fluoride inhibits enolase, and is used in water and toothpaste to keep oral bacteria from growing and creating dental caries. Red blood cell pyruvate kinase deficiency can lead to mild anemia. which of the following glycolytic intermediates would accumulate in common in both of these conditions?
Pyruvate only
Glucose only
Pep only
3-phosphoglycerate only
2-phosphoglycerate only
Glyceraldehyde 3-phosphate only
1, 2, 3
4, 5, 6
1, 3, 5
2, 4, 6
Pyruvate only
Glucose only
Pep only
**3-phosphoglycerate only**
**2-phosphoglycerate only**
**Glyceraldehyde 3-phosphate only**
1, e, 3
**4, 5, 6**
1, 3, 5
2, 4, 6
77
Differential Regulation
78
Describe the Cori Cycle
79
Why Enzyme Kinetics?
80
Enzyme Kinetics
81
What are the two Major Assumptions in Enzyme Kinetics
82
K1
Rate constant for ES complex Formation
83
K2
Rate constant for ES complex Breakdown
84
K3
Rate consent for Product formation
85
Derive the Michaelis-Menton Equation based on the assumptions made.
86
What happens when V = 1/2 Vmax
87
Km for glucokinase vs. Hexokinase
Km for Glucokinase is about 7mmolar which is much higher than km for hexokinase
88
Is Km a true measure for affinity?
Km for Glucokinase is about 7mmolar which is much higher than km for hexokinase
This is is not a true measurement for affinity
89
Graphical Representation of the Michaelis Menton Equation
90
Lineweaver Burk Derivation
91
Lineweaver Burk Plot
92
Km and Vmax
93
Competitive Inhibitors
94
Non-Competitive Inhibitors
95
Explain the concept of Apparent Km
When an inhibitor is present you need more substrate to kickoff inhibitor and get to the necessary km that is half Vmax. That’s why we call it the apparent km because the concentration is much more not because the actual km has changed but because you also have to take into account additional substrate amount to kick off the inhibitor.
96
How do most drugs effect enzyme activity?
Most drugs inhibit enzyme activity.
97
Lineweaver Burk of Competitive Inhibition
98
Lineweaver Burk Plot for Non-Competitive Inhibition
99
If the Vmax of enzyme 1 is 20 units per sec and the Vmax of enzyme 2 is 10 units/sec then the Km”s of the enzymes can be related by which of the following?
The km of enzyme 1 is one half that of enzyme 2
We cannot determine it from the data we have.
We cannot determine it from the data we have.
100
Summary of Enzyme Kinetics
101
Summary of Inhibitors in Enzyme Kinetics
102
Hyperglycemia
103
An individual has inherertided a mutation in the regulatory subunit of pea which has greatly reduced affinity for camp during fasting this mutation lead to which one of the following?
## Footnote
Hypoglycemia
Hyperglycemia
Hyperactive muscle glycolysis
Hyperactive liver glycolysis
Hypoglycemia
104
## Footnote
A classification of pre-obese refers to a BMI of
15-18.4
18.5 -24.9
25-29.9
30-39.9
\> 40
25-29.9
105
What is the velocity of an enzyme catalyses reaction when [S] is 0.5 k
Vmax
0. 25 vmax
0. 33 vmax
0. 5 vmax
0. 67 vmax
0. 75 vmax
0.33 vmax
106
Dietary fructose is obtained primarily from which one of the following?
Starch
Milk
Apples
French Fries
Pizza
Apples
107
Fructose Metabolism
108
Fructose and Galactose come from...
Fructose and Galactose come from dishaccarides.
They enter glycolysis but in different ways.
109
Where does all of our fructose get metabolised?
Liver metabolizes all of our Fructose
110
Features of Fructokinase
This enzyme has a low Km and High Vmax\* — Low substrate concentration and works very fast.
111
Aldolase B
Aldolase B — Found in Liver— Only in liver— F1,6BP
112
Which key regulatory step is skipped when fructose enters glycolysis?
Hexokinase
Glucokinase
Gructokinase
PFK-1
PFK-2
Pyruvate
PFK-1 — Which means it’s hard to regulate
113
IV Fructose Loading
115
Is IV Fructose loading the same as eating excess fructose?
No, Direct injection of fructose into the veins not through eating
116
Fructokinase Velocity and Substrate Concentration
High Vmax but low Km
117
Essential Fructosuria
118
Explain what happens when you give someone IV Glucose
If you give someone IV fructose you get lots of lactic acid which overcomes the buffering capacity of the blood and blood pH begins to drop — not good
Individuals given IV fructose almost died so we use IV glucose instead.
119
Hereditary Fructose Intolerance
121
Is Essential Fructosuria Worrysome?
No ill effects from this disorder. But because there’s fructose in the urine it gives a positive test for a reducing sugar test. Glucose also tests positive which is used to test for diabetes so fructosuria can misleadingly tell you someone has diabetes
123
Explain how Hereditary Fructose Intolerance is Managed
Self-limiting disease — if born with mutation — they would throw up after apple sauce and you’d then stop giving it to them. The treatment is an appropriate diet that doesn’t have fructose.
124
Aldolase A and C vs. Aldose B
Aldolase A and C cannot split F-1,6-BP but B can split either F1P or F16BP
125
What happens when F1P is high
When F1P is high you have a problem with glycogen degradation
126
How Does Uric Acid Effect the Kidney?
Uric acid blocks ability of the kidney to remove lactate from the blood making acidosis worse.
127
The net yield of ATP when fructose is converted to 2 Molecules of Pyruvate is:
## Footnote
No ATP
1 ATP
2 ATP
3 ATP
4 ATP
2 ATP
128
How Much Net Yeild of ATP does Fructose use compared to Glucose
Fructose has the same net yield of ATP as Glucose
129
Galactose Metabolism
130
What is Galactosemia?
131
Galactosemia Classic Type
132
Non-Classical Galactosemia
133
What foods have Galactose?
Galactose is from anything derived from milk. E.g. Cheese
134
Galactose vs. Glucose
Galactose is an epimer of Glucose — Hydroxyl is on opposite side at carbon 4 of glucose.
135
UDP-Glucose
UDP-Glucose is an Activated Glucose
UDP-Glucose is always regenerate so you only need small amount
138
The Polyol Pathway
140
How do you treat Galactosemia?
By removing Galactose from Diet.
141
Phosphoglucomutase
Phosphoglucomutase is necessary to get glucose from Glycogen.
142
Digestion and Absorbtion of Carbohydrates
143
Starch
144
Dietary Carbohydrates
145
Digestion of Starch
146
Galactitol
Galactitol creates an osmotic Imbalance in the eye.
147
Cataract Formation in Galactosemia
Rapid formation of cataracts in both classical and non-classical
148
Starch Digestion Continued
149
The net yield when one mole of galactose is converted to 2 moles of pyruvate is:
0 Moles of ATP
1 Mole of ATP
2 Moles of ATP
3 Moles of ATP
4 Moles of ATP
2 Moles of ATP
Just like glucose it only takes one ATP to get from Galactose to G6P just like one Glucose takes one ATP to Get to G-6P
150
Brush Border Membrane of Intestinal Epithelial Cells
151
Sucrase Iso-Multase Complex
152
Glucoamalyse Complex
153
More Brush Border Enzymes
154
Isomaltase Enzyme Activity
155
Sucrase, Isomaltase, and glucoamylase enzyme activities
156
Lactase Activity
157
Lactose Intolerance
158
Transport of Monosaccharides
## Footnote
Transporter allows glucose to be concentrated inside the lumen.
Fructose only transported via a Facilitated transporter.
Glucose transport is coupled to sodium transport
Sodium potassium ATP-ase Na is primary transported and Glucosed is secondarily transported.
Sodium gradient drives Glucose active transport
Sodium Potassium ATP-ase uses ATP and 3 Na in to drive movement of glucose and galactose in.
160
Glucose Accumulation and Diabetes
Glucose accumulation, from diabetes, will be reduced to sorbitol which will get trapped in the eye and forms cataracts.
161
High Glucose levels and HbA1C levels?
High glucose leads to non-enzymatic glycosylation— hbA1C is elevated because it is a glycosylated protein. HbAIC is used as a measure of glycemic control, how well you can control your blood sugar. Is it greater than the normal 5%?
162
What happens to Nervous System when Glucose levels are high?
Nervous system proteins also gets glycosylated which leads to neuropathy.
165
Glut -1
GLut1 is a low km transporter
166
Glut 2
167
Glut 3
Glut 3— two glucose transporters are needed to get glucose into the neurons.
168
Glut 4
169
Glut 5
170
Glut 1 Deficiency Syndrome
171
Glycolysis and Diabetes
172
Glycolysis and Diabetes in the Liver
175
Where do Proteins Get Digested?
Proteins get digested in the stomach.
176
Gluconeogenesis
177
Reactions that reverse the Pyruvate Kinase Step of Glycolysis
178
Reaction that Reverses the PFK-1 Reaction
179
Reaction that Reverses Glucokinase (Liver and Pancrease)/Hexokinase (all other tissues)
180
Are fats and carbs digested in the somach?
Fats and carbs are not digested in the stomach.
182
Inflammation of the Pancreas
Inflammation of Pancreas will lead to pancreatic amylase in the blood which makes it a marker for Pancreatic inflammation.
183
Compartmentation issues in Gluconeogenesis
184
Draw out the overview of regulation of Gluconeogenesis
185
Regulation of Glycolysis and Gluconeogenesis when levels of blood sugar is high
186
Regualtion of Glycolysis and Gluconeogenesis when Glucose levels are low in the blood
187
Summary of Gluconeogenesis
188
Signal Transduction
189
Structure of the Insulin Receptor
190
Tyrosine Kinase Activity
191
What is IRS-1
192
Glucagon Receptor
193
G-Proteins
194
G - Protein Cycle
195
G-Protein Regulation
197
Cholera and Pertussis
198
Diabetes Revisited
199
Summary of Signal Transduction
208
Transporters...
Transporter allows glucose to be concentrated inside the lumen.
209
Fructose and Transport
Fructose only transported via a Facilitated transporter.
210
What is Glucose Transport Coupled With?
Glucose transport is coupled to sodium transport
211
Primary vs. Secondary Transport
Sodium potassium ATP-ase Na is primary transported and Glucosed is secondarily transported.
212
What drives glucose into serosal side of the intestine?
Sodium gradient drives Glucose active transport
213
What does the sodium potassium pump use?
Sodium Potassium ATP-ase uses ATP and 3 Na in to drive movement of glucose and galactose in.
222
NASH
Non-Alcoholic Steatohepatitis
NASH— Fat accumulation in the liver. — Found in diabetics with poor control of sugar levels.
223
Young girl has been diagnosed with type 1 diabetes. one of her symptoms was blurry vision, which occurred tue to which of the following:
## Footnote
Elevated glucose in the urine
Elevated glucose in the blood
The production of HbA1c
Altered Glut4 Proteins
Reduction of Glucose
Oxidation of glucose
Reduction of Glucose — ( Glucose going to sorbitol is a reduction of glucose — sorbitol leads to blurred vision)
224
Which one of the following enzymatic reactions needs to be bypassed in synthesizing glucose from pyruvate.
## Footnote
G3PDH
Enolase
Phosphoglyrcerate kinase
Pyruvate kinase
Aldolase
Pyruvate kinase
229
Starting with two molecules of lactate, ho many molecules of ATP/GTP are required to synthesize one glucose molecule?
## Footnote
2
3
4
5
6
7
8
6
230
Anabolic vs. Catabolic
Always takes more energy to make something than to degrade it.
231
What is a symptom for someone with a defect of FATTY Acid Oxidation
Hypoglycemia because a lack of energy to perform gluconeogenesis.
245
If the GTPase activity of a G protein were mutated, and rendered inactive, which one of the following would occur?
Inactivation of a G protein activity
Constant activation of G protein Activity
No effect on G Protein
Constant activation of G protein Activity
246
Galactose Metabolismm
