MCM - Carb Metabolism Flashcards
1
Q
What chemical reaction do all cells carry out for energy?
A
Glycolysis
2
Q
What are 3 major monosaccharides that can be used in Glycolysis
A
Glucose, Fructose, and Galactose
3
Q
Which cell group can only use Glycolysis
A
Red Blood Cells
4
Q
Whats the brain’s primary source of energy when in “fed” state
A
Glycolysis
5
Q
How does Glucose enter a cell
A
Through the use of GLUT transporters; facilitated diffusion
6
Q
How many types of GLUT are there for uptake of solely Glucose
A
GLUT 1, GLUT 2, GLUT 3, GLUT 4
7
Q
GLUT 1 characteristics
A
Found everywhere, but high concentration in RBC’s and Brain; high affinity
8
Q
GLUT 2 Characteristics
A
Main transport in liver; low affinity. But picks up any source of glucose
9
Q
GLUT 3 Characteristics
A
Main transporter in neurons; High Affinity
10
Q
GLUT 4 Characteristics
A
Present in skeletal muscle, heart, adipose tissue; Insulin Dependent
11
Q
Where is GLUT 4 located in the cell
A
Sequestered in vesicles until insulin is bound
12
Q
What enables GLUT 4
A
Binding of insulin, which releases GLUT 4 to the plasma membrane
13
Q
Basic Steps of Glycolysis
A
1 molecule of glucose -> generate 2 molecules of pyruvate; generate 2 ATP; generate 2 NADH
14
Q
Is glycolysis Anaerobic or Aerobic
A
Anaerobic
15
Q
Where does glycolysis occur in the cell
A
Cytoplasm
16
Q
First Part of Glycolysis
A
Phosphorylation of Glucose to Glucose-6 Phosphate by Hexokinase/Glucokinase
17
Q
What main energy source does Glycolysis require
A
One molecule of ATP
18
Q
Differences between Hexokinase and Glucokinase
A
Hexokinase is the general enzyme; glucokinase is specific to the liver and pancreatic Beta cells
19
Q
What is the Rate Limiting Step of Glycolysis
A
The phosphorylation of Fructose-6 Phosphate to Fructose 1,6-biphosphate
20
Q
What enzyme performs the first reaction of Glycolysis
A
Hexokinase/Glucokinase
21
Q
What enzyme performs the Rate Limiting Step of Glycolysis
A
Phosphofructokinase-1; PFK-1
22
Q
What does Phosphofructokinase do
A
Phosphorylates Fructose 6-Phosphate to Fructose 1,6-biphosphate
23
Q
Does Phosphofructokinase use ATP
A
Yes
24
Q
What does the phosphorylation of G3P produce
A
One NADH; no use of ATP
25
Where does the first pay off of Glycolysis occur
When G3P is phosphorylated
26
What is the second pay off stage of Glycoysis
Conversion of 1,3-BPG to 3-PG; 2 ATP created
27
What is the third and final pay off stage of Glycolysis
Formation of Pyruvate from Pyruvate Kinase; 2 ATP created; also irreversible
28
What are the 3 pay-off stages of Glycolysis
1. Phosphorylation of G3P; 1 NADH
2. Conversion of 1,3BPG to 3-PG; 2 ATP
3. Formation of Pyruvate; 2 ATP
29
What enzyme phosphorylates Glucose to Glucose 6-Phosphate
Hexokinase (general)/ glucokinase (liver and pancreas)
30
What enzyme Phosphorylates Fructose 6-P to Fructose-1,6- Biphosphate
Phospofructokinase-1
31
Which enzymes in Glycolysis use ATP
Phospofructokinase-1 and Hexokinase (general)/ glucokinase (liver and pancreas)
32
Which enzyme takes 1,3-BPG to 3-phosphogylcerate
Phosphoglycerate Kinase
33
Which enzyme takes Phosphoenolpyruvate to Pyruvate
Pyruvate Kinase
34
Which enzymes in Glycolysis produce ATP via their reaction
Pyruvate Kinase and Phoshoglycerate Kinase
35
Which enzyme takes Glyceraldehyde 3-P to 1,3-Bisphosphoglycerate
Glyceraldehyde 3-P dehydrogenase
36
Which enzyme in Glycolysis produces one NADH
Glyceraldehyde 3-P dehydrogenase
37
What are the three irreversible steps of Glycolysis
1. Hexokinase/Glucokinase (Trap Glucose)
2. Phosphofructokinase (Add another Phosphate)
3. Pyruvate Kinase (Split the 6 Carbon molecule to two 3 carbon molecules)
38
Hexokinase has a low or high affinity
High affinity; binds all glucose
39
Glucokinase has a low or high affintiy
Low affinity
40
What is Hexokinase inhibited by
G6P; the product of this enzymes action
41
What is Glucokinase inhibited by
Nothing really, but Glucagon
42
When is Glucokinase most active
High Glucose
43
Insulin induces the synthesis of
Glucokinase
44
Glucagon inhibits the synthesis of
Glucokinase
45
PFK-1 Activators
AMP, Fructose 2,6-Bisphosphate
46
What makes Fructose 2,6-Bisphosphate
PFK-2
47
PFK-1 Inhibitors
ATP, Citrate (TCA Cycle)
48
When is PFK-1 Activated; when its phosphorylated or dephosphorylated
Dephosphorylated
49
Hormonal Regulation of PFK-1
Glucagon Inhibits; Insulin Activates
50
What activates Pyruvate Kinase
Fructose 1,6-Bisphosphate and Glucagon
51
What inhibits Pyruvate Kinase
ATP, Alanine, and Glucagon
52
High Insulin Effect on Pyruvate Kinase
Stimulates protein phosphatase, dephosphorylation of PK, activate
53
High Glucagon Effect on Pyruvate Kinase
cAMP activates PKA, phosphorylation, PK Inhibited
54
Glucose 6-Phosphate Use in Other Pathways
Precursor for the PPP
Can be converted to Glucose 1-Phosphate
{used in galactose metabolism, glycogen synthesis, ironic acid pathway}
55
Glucose 6-Phosphate's Outcome in the Pentosephosphate Pathway
Ribose and NADPH
56
Use of Ribose
For DNA Synthesis
57
Use of NADPH
Resythesizing Glutathione, a Selenium co-factor for getting rid of Hydrogen Peroxide
58
What are some fates of Pyruvate
1. Reduced to lactate; to regenerate NAD+ in anaerobic conditions
2. Oxidized in TCA cycle to Acetyl CoA and the CO2
3. Converted to Alanine; used in gluconeogenesis and protein synthesis
4. Converted to ethanol
59
Disorders of Glycolysis effect what two areas the most
The brain and the RBC's
60
What do disorders of glycolysis usually cause
hemolytic anemia; because RBC's cannot maintain there molecular gradients
61
Which enzyme is most affected in glyosis disorders
Pyruvate Kinase (95%)
62
What are the 2 types of Diabetes
1. Type 1- autoimmune disorder affecting the Beta Cells of the Pancreas in the Langhorn area
2. Type 2: Insulin resistance, usually caused by being extremely overweight
63
Other Potential causes of Diabetes than obesity
mutations, aberrant conversion of proinsulin to mature insulin, defective insulin receptor
64
What is the normal blood glucose range; fasting
70-100 mg/dL
65
What is the normal blood glucose range; fed
<140 mg/dL
66
Prediabetic glucose range; fasting
100-125 mg/dL
67
Prediabetic glucose range; fed
>125 mg/dL
68
Tarui Disease
Deficient in PFK-1; least common Glycolysis Disorder; exercise induced muscle cramps and weakness
69
How much glucose does the brain need in one day
120 grams
70
How much glucose is present in body fluids
20 grams
71
How much glycogen is readily available in the body
190 grams
72
How long can glycogen stores supply the body
About one day without eating glucose
73
Where does Gluconeogenesis Occur
Liver, Kidney, and Small Intestine
74
What does Gluconeogenesis accomplish
converts pyruvate back to glucose
75
What can be fed into gluconeogenesis
lactate, amino acids, and glycerol
76
What are the two enzymes where gluconeogenesis converts (2x) pyruvate
Pyruvate Carboxylase and PEP Carboxylase
77
What enzyme does Gluconeogenesis use to bypass PFK-1 process
Fructose 1,6-bisphosphatase
78
What enzyme does Gluconeogenesis use to bypass hexokinase/glucokinase
glucose 6-phosphatase
79
Positive Regulators of Gluconeogenesis
Glucagon, citrate, cortisol, thyrozine, acetyl CoA
80
Positive regulators of Glycolysis
Glucose, insulin, AMP, Fructose 2,6-BP, Fructose 1,6-BP
81
Negative regulators of Gluconeogenesis
ADP, AMP, Fructose 2,6-BP`
82
Negative regulators of Glycolysis
Glucagon, ATP, citrate, Glc 6-P, Fructose 6-P, Alanine
83
4 enzymes that gluconeogenesis uses to bypass glycolysis irreversible steps
1. Pyruvate Carboxylase
2. Phosphoenolpyruvate Corboxykinase
3. Fructose 1,6-BP
4. Glucose 6-phosphatase
84
What is Pyruvate Carboxylase
Mitochondrial Enzyme; activated by acetyl CoA and Cortisol
85
Can Oxaloacetate leave the mitochondria
No; its impermeable
86
How does Oxaloacetate need to be altered to leave mitochondria
Reduced to malate
87
How is Malate changed once it leaves the mitochondria
Re-Oxidized to Oxaloacetate
88
PEP Carboxykinase
Decarboxylation and phosphorylation of Oxaloacetate to PEP
89
What activates PEP Carboxykinase
Cortisol, Glucagon, Thyroxine
90
What is the Rate Limiting step of Gluconeogenesis
Fructose 1,6-Bisphosphatase
91
What is Fructose 1,6-Bisphosphatase Activated by
Cortisol and Citrate
92
What is Fructose 1,6-Bisphosphatase Inhibited by
AMP and F 2,6-BP
93
What is the last step of Gluconeogenesis
Dephosphorylation of Glucose 6-Phosphate to Glucose
94
What enzyme takes Glucose 6-Phosphate to Glucose
Glucose 6-Phosphatase
95
What activates Glucose 6-Phosphatase
Cortisol
96
Where is Glucose 6-Phospatase found
Liver, Kidney, Small Intestine and Pancreas
I.E. Where Gluconeogenesis occurs
97
Where in the cell is Glucose 6-Phosphatase found
The lumen of the ER
98
How does glucose 6-P get into the lumen of the ER to get to Glucose 6-Phosphatase and get back glucose back out
G6P Transporter
and
GLUT7 transporter back into the cytoplasm
99
Cori Cycle Process
2 lactate from the muscle transported to the liver
Once in the liver 2 lactate into 2 pyruvate
Once 2 pyruvate you get Glucose with a 4 ATP investment via Gluconeogenesis
100
Name Four Precursors to Gluconeogenesis
1. Glycerol (Carb)
2. Propionate (from odd-numbered fatty acids)
3. Alanine (Protein Degradation)
4. Amino Acids (Protein Degradation)
101
Name two other sugars that can go into Gluconeogenesis
1. Galactose
| 2. Fructose
102
Fructose 1,6-BP Deficiency Consequences
Cannot have the payoff of Gluconeogenesis
103
Von Gierke Disease
Mutations in the catalytic site in GSD 1a
| Present with hepatomegaly due to buildup of glycogen in the liver
104
Sucrose Structure
Fructose and Glucose
105
What is Sucrose Cleaved by
Sucrase
106
Lactose Structure
Galactose and Glucose
107
What is Lactose cleaved by
Lactase
108
Which GLUT Transporter uptakes Fructose
GLUT 5
109
SGLT1 uptakes which two sugars
Galactose and Glucose
110
Franconi-Bickel Syndrome; Overall effect
GLUT 2 mutation; failing to absorb galactose, glucose, and fructose
111
Location of GLUT 2 Tranporter
Liver, Pancreatic Beta Cells, Enterocytes, and renal tubular cells
112
What process takes Glucose to Fructose
The Polyol Pathway
113
What is the Polyol Pathway
Glucose reduced to Sorbitol, Sorbitol oxidized to Fructose
114
What two enzymes are utilized in the Polyol Pathway
Aldose Reductase and Sorbitol Dehydrogenase
115
Cells lacking Sorbitol Dehydrogenase allow build up of sorbital triggering what
Cataracts
116
Fructose Caviet in entering Glycolysis
Can by-pass PFK-1, the rate-limiting step of Glycolysis
| This leads to excess Pyruvate, furthering to storage of Fatty Acids into Triacylglycerols, leading to excess Fat
117
High Fructose Corn Syrup Effect
Can bypass PFK-1 and be stored as fat easier
118
Deficiency of Galactokinase leads to
Build up of Galacitol; leading to cataracts
119
Deficiency in Glucose 1P uridyltransferase
Leads to accumulation of Galacitol because of the side reaction that takes place
120
What does the Pentose Phosphate Pathway Produce
1. Sugar needed for DNA and RNA formation
| 2. NADPH; used to remake Glutathione
121
Where does the P.P.P. take place
Cytosol
122
What does G6P Dehydrogenase produce from the Pentose Phosphate Pathway
NADPH
123
What is the rate limiting step of the P.P.P.
G6P Dehydrogenase
124
G6PD Deficiency
Accumulation of hydrogen peroxide, leads to hemolytic anemia
125
Which Part of the P.P.P. is irreversible
The Oxidative Phase
126
What does the Oxidative Phase of the P.P.P. produce
NADPH and Ribulose 5-P
127
What Part of the P.P.P. is reversible
The Non-Oxidative Phase
128
What does the Non-Oxidative Phase Produce
Several Metabolites that can go into glycolysis and gluconeogenesis
129
When is the Oxidative side of the P.P.P. favored
When cells are rapidly dividing; in need of Ribulose 5-P
130
When there is a high demand for NADPH what does the P.P.P. do
Non-Oxidative products channeled into gluconeogenesis for re-entry into the P.P.P. Oxidative Pathway
131
Where is an area where P.P.P. activity is very high
Phagocytic Cells
132
What kind of chain is produced with the alpha 1,4
Straight chain
133
What kind of chain is produced with the alpha 1,6
Branches
134
Which end of glycogen is free to react?
The non-reducing end
135
Which end of glycogen is not free to react
The reducing end
136
What is the hallmark of the non-reducing end
An OH- group at Carbon 4
137
Where does Glycogen Store
The Liver and Muscle
138
How is glycogen stored inside the liver and muscle
Inside granules; containing the enzymes needed for glycogen metabolism
139
What is the function of Liver Glycogen
To regulate blood glucose
140
What is the function of Muscle Glycogen
To provide a reservoir of glucose for physical activity
141
What is the first step of Glycogenesis
Trapping and Activation of Glucose; hexokinase/Glucokinase phosphorylyze glucose in liver and muscle cells (in the cytosol of the respective cells)
142
What is the rate limiting step of Glycogensis
Glycogen Synthase; adds UDP-Glucose to non-reducing end of glycogen chain
143
What branches the growing glycogen chain
At about 11 residues a fragment is broken off and the reattached elsewhere to with an alpha 1,6 chain via branching enzyme
144
How does branching effect the solubility of glycogen
Increases the solubility as branching is increased
145
What is the rate limiting step of Glycogenolysis
Glycogen Phosphorylase
146
What does Glycogen Phosporylase do
Catalyzes the cleavage of glucose residues as a G1P from the non-reducing end
147
How does the alpha 1,6 bond break
With debranching enzyme, adding the 3 residues back to the straight chain, cleaving the last alpha 1,6 bond that is left to release free glucose
148
Ratio of Glu-1-P to Glu
10:1
149
Fate of Liver Glu-1-P
converted to Glu-6-P and then to Glu. Free glucose released to blood
150
Fate of Muscle Glu-1-P
Myocytes and cardiac myocytes lack glucose-6-phosphatase. So they use the Glu-1-P to generate energy via glycolysis and the TCA cycle
151
What are 2 important reasons to regulate glycogen metabolism
1. Maintain Blood Sugar
| 2. Provide Energy to Muscle
152
What are the 2 Key enzymes in regulating glycogen metabolism
1. Glycogen Synthase
| 2. Glycogen Phosphorylase
153
What does Glycogen Synthase do
makes alpha 1,4 links and is the rate limiting step of glycogensis
154
What does Glycogen Phosphorylase do
Cuts the alpha 1,4 links and the is the rate limiting step of glycogenolysis
155
When is Glycogen Synthase active
When it is in the Dephospho form
156
When is Glycogen Phosphorylase Active
When it is in the Phospho form
157
When is Glycogen Synthase Inactive
When it is in the Phospho Form
158
When is Glycogen Phosporylase Inactive
When it is in the Depospho Form
159
In which state, fed or fasting, is Glycogenesis favored
Fed
160
In which state, fed or fasting, is Glycogenolysis favored
Fasting
161
Which state is favored while exercising, glycogenolysis or glycogenesis
Glycogenolysis
162
What are the four key proteins involved in Insulin Regulation
1. GLUT 4; insulin sensitive GLUT transporter
2. Protein Kinase B (PKB)
3. Protein Phosphatase 1 (PP1)
4. Glycogen Synthase Kinase 3 (GSK 3)
163
Effect of Insulin Binding on Glycogen Synthase
Binds, excites PKB. PKB excites PP1 which phosphorylates Glycogen Synthase activating it
164
Effect of Insulin Binding on Glycogen Phosphorylase
Insulin binds, excites PKB. PKBB Excites PP1. PP1 inhibits Pyruvate Kinase and dephosphorylates Glycogen Phosporylase
165
Type 2 Diabetes Blood Criteria
Normal: 70-100mg fasting; <140mg fed
PreDiabetic: 100-125mg fasting; >140 fed
Diabetic: >126mg fasting; >199mg Fed
166
Key Enzymes and secondary messengers of Glucagon Regulation
```
G Protein
Adenylate Cyclase and cAMP
Protein Kinase A
Protein Phosphatase 1
Phosphorylase Kinase
```
167
Net Result of Insulin Binding
Glycogen is stored
168
Net Result of Glucagon Binding
Glycogen is broken down for glucose
169
Effect of Glucagon Binding on Glycogen Synthase
Phosphorylates Glycogen Synthase; deactivating it
170
Effect of Glucagon Binding on Glycogen Phosphorylase
Dephosphorylates Glycogen Phosphorylase; activating it
171
Effect of Epinephrine binding to muscle or liver during exercise
Same as Glucagon
172
Glycogen Storage Disease; Genetic Traits
Autosomal Recessive
173
Glycogen Storage Diseases
1. Glycogen Synthase Defective
2. Von Gierke Disease
3. Pompe Disease
4. Cori Disease
5. Anderson Disease
6. McArdle Disease
7. Hers Disease
174
What enzyme is defective in Glycogen Synthase Defect
Glycogen Synthase
175
What enzyme is defective in Von Gierke Disease
Glucose 6-Phosphatase
176
What enzyme is defective in in Pompe Disease
Acid Maltase
177
What enzyme is defective in Cori Disease
Debranching Enzyme
178
What enzyme is defective in Anderson Disease
Glucosyl (4:6) Transferase
179
What enzyme is defective in McArdle Disease
Muscle Glycogen Phosphorylase
180
What enzyme is defective in Hers Disease
Liver Glycogen Phosphorylase
181
Difference between McArdle Disease vs. Hers Disease
McArdle: in Muscle GP; muscle form of isozyme is activated by AMP, Ca-CaM, and G Actin
Hers: in Liver GP; inactivated by free glucose and unaffected by AMP
182
G-3-P and DHAP have an equilibrium; DHAP can also go
Into FA Synthesis and TAG Synth
