Carbohydrate Metabolism 1 Flashcards
(131 cards)
1
Q
What is the ideal blood glucose concentration?
A
Around 100 mg/dL(5.6 mM)
2
Q
Briefly state some consequences high blood sugar
A
- Long term damage to the retina
- long term damage to the kidney
- long term damage to nerves and blood vessels
- coma
3
Q
What is the normal glucose concentration in peripheral blood? Give a range and average
A
5.6 mM ( 4-6 mM)
4
Q
What are the 4 glucose transporters and what are the most important ones?
A
GLUT 1 - GLUT 4
GLUT 2 and GLUT 4 are the most important
5
Q
Why are GLUT 2 and GLUT 4 the most significant glucose transporters?
A
They are only located in specific cells and are highly regulated
6
Q
Describe GLUT 2
A
A low-affinity transporter in hepatocytes and pancreatic cells
7
Q
What is the specific scenario/function of GLUT 2?
A
- After a meal when blood in the hepatic portal vein is rich in glucose
- GLUT 2 captures glucose primarily for storage
8
Q
What is the Km of GLUT 2?
A
15 mM
9
Q
What is the consequence when blood glucose concentration drops below the Km of the GLUT 2 transporter?
A
Much of the remainder bypasses the liver and enters peripheral circulation.
10
Q
Liver will pick up glucose in proportion to its….
A
Concentration in the blood(first order kinetics)
11
Q
What does the Glucose sensor for insulin release comprise of?
A
In the B-islet cells of the pancreas, GLUT 2, along with glycolytic enzyme glucokinase
12
Q
Where is GLUT 4 located? What type of blood does it regulate?
A
Adipose tissue and muscle
Regulates glucose concentration in peripheral blood
13
Q
What is Km?
A
The concentration of substrate when an enzyme is active at half of its maximum velocity (vmax)
14
Q
Explain the correlation of km and enzyme affinity for the substrate
A
The lower the km the higher the enzyme’s affinity for the substrate
15
Q
What can increase the rate of glucose uptake in adipose and muscle tissue?
A
Insulin
16
Q
What is the normal Km of GLUT 4 ?
A
About 5 mM
17
Q
How does insulin increase the uptake of glucose by adipose and muscle tissue?
A
Insulin stimulates the movement of additional GLUT 4 transporters to the membranes by a mechanism involving exocytosis
18
Q
What is the consequence of GLUT Km being 5 mM?
A
Transporter is saturated when blood glucose levels are just a bit higher than normal
19
Q
How can GLUT 4 transporters increase their take intake of glucose?
A
By increasing the number of GLUT 4 transporters on their surface
20
Q
Decreased insulin ______________ the number of plasma membrane GLUT 4 transporters and…
A
Decreased
Endocytosis of cytoplasmic vesicles with membrane-bound GLUT 4 transporters
21
Q
Increased insulin ____________ the number of plasma membrane GLUT 4 transporters and…..
A
Increased
Exocytosis and fusion of vesicles with plasma membrane
22
Q
Why in certain cells, such as red blood cells is glycolysis so important?
A
Glycolysis represents the only energy yielding pathway as they lack a mitochondria
23
Q
All cells carry out …
A
Glycolysis
24
Q
Why do red blood cells extrude their mitochondria?
A
Helps them carry oxygen for 2 reasons :
- Maximizing volume available for hemoglobin, the primary oxygen-carrying protein
- Stopping the red blood cell from utilizing the oxygen it’s supposed to be carrying to oxygen- depleted bodily tissues
25
What does glycolysis produce?
2 pyruvate molecules
A modest amount of energy
26
What purpose does glycolysis serve in the liver?
Helps liver convert glucose to fatty acids for storage
27
Give the first steps in the glycolysis pathway
1. Glucose is phosphorylated by ATP( gives ADP)(catalyzed by Mg 2+ and Hexokinase Glucokinase)
2. Isomerase converts Glucose 6-P to Fructose 6-P
3. Phosphorylation from ATP and catalysis from PFK-1 (Phosphofructokinase), converts Fructose 6-P to Fructose 1,6-bis P
28
Give the steps in the second part of the steps of glycolysis
4. Aldolase converts Fructise 1,6 bis P to Glyceraldehyde 3-P and Dihydroxyacetone-P
5. NAD+,Pi and Glyceraldehyde-3-P dehydrogenase convert Glyceraldehyde 3-P to 1,3-Biphosphoglycerate
6. 1,3-Biphosphoglycerate is phosphorylated by ATP and Phosphoglycerate kinase to 3-phosphoglycerate
(In RBC, 1,3- Biphosphoglycerate becomes 2,3-biphosphoglycerate and becomes 3-phosphoglycerate
29
Give the final steps Glycolysis(from 3-Phosphoglycerate go down)
7. 3-Phosphoglycerate reacts with mutase to become 2-Phosphoglycerate
8. 2-Phosphoglycerate reacts with enolase to become phosphoenrolpyruvate(PEP)
9. Phosphoenrolpyruvate is dephosphorylated by ADP and pyruvate kinase to form pyruvate
30
What happens to pyruvate in the absence of oxygen?
Pyruvate is converted to lactate by lactate dehydrogenase and NADH which is converted to NAD+
31
Give 3 differences between hexokinase and glucokinase
1. Hexokinase is present in most tissues while Glucokinase is in hepatocytes and pancreatic B-islet cells
2. Hexokinase has a Low Km while Glucokinase has a high Km
3. Hexokinase is inhibited by glucose-6-phosphate while glucokinase is induced by insulin in hepatocytes
32
In the first steps of glucose metabolism in any cell are phosphorylation by kinase enzymes. Why is that?
To prevent the glucose from leaving via the transporter
33
What is the rate limiting enzyme and main control point in glycolysis?
Phosphofructokinase-1
34
What is the function of. phosphofructokinase 1/ PFK-1 ?
Fructose-6-phosphate is phosphorylated to fructose 1,6-bisphosphate using ATP and PFK 1
35
What chemicals inhibit and activated PFK-1?
ATP inhibits PFK-1
AMP activates PFK-1
36
What do high levels of citrate in a cell indicate? Why?
They indicate the cell is producing sufficient energy
Citrate in an intermediate of the citric acid cycle
37
What is the function of PFK-2 (and by extension insulin) in glycolysis?
Insulin activates Phosphofructokinase-2 ( PFK-2) which converts a small amount of fructose 6-phosphate to fructose 2,6-biphosphate (F2,6-BP)
38
What is the function of Fructose 2,6 -bisphosphate in glycolysis?
It activates OFK-1,Therefore insulin indirectly activatesPFK-1 while glucagon indirectly inhibits PFK-1
39
What is the function of glucagon in glycolysis?
Glucagon inhibits PFK-2, lowering Fructose 2,6 bisphosphate and inhibiting PFK- 2
40
Where is PFK -2 found?
In the liver
41
How does phosphofructokinase-2 allow glycolysis to continue when ATP requirements are satisfied?
By activating PFK-1, inhibition caused by ATP is overridden
42
What happens to metabolites of glycolysis when ATP requirements are already met?
They are fed into the production of glycogen, fatty acids and other storage molecules
43
What is the function of Glyceraldehyde-3-Phosphate dehydrogenase?
It catalyze the an oxidation and addition of inorganic phosphate (Pi) to it’s substrate, glyceraldehyde 3-phosphate
44
What is the effect of Glyceraldehyde-3-phosphate dehydrogenase after producing glyceraldehyde 3-phosphate?
A high-energy intermediate 1,3-biphosphoglycerate and reduction of NAD+ to NADH
45
What is the rate limiting enzyme of fermentation?
Lactate dehydrogenase
46
What is the rate limiting enzyme of glycogenesis?
Glycogen synthase
47
What is the rate limiting enzyme of glycogenolysis?
Glycogen phosphorylase
48
What is the rate limiting enzyme of gluconeogenesis?
Fructose-1,6- bisphosphatase
49
What is the rate limiting enzyme of the pentose phosphate pathway?
Glucose-6-phosphate dehydrogenase
50
What is a substrate level phosphorylation reaction?
A reaction where ADP is phosphorylated to ATP
51
What is the function of 3-phosphoglycerate kinase?
3-phosphoglycerate kinase transfers the high energy phosphate from 1,3-bisphosphoglycerate to ADP
This forms ATP and 3-phosphiglycerate
52
What is feed-forward activation?
The product of an earlier reaction stimulates a later reaction in the pathway/reaction
53
How is Pyruvate Kinase activated?
Activated by fructose-1,6-bisphosphate from the PFK-1 reaction (feed-forward reaction)
54
What is the funcation of pyruvate kinase?
The last enzyme in aerobic glycolysis, it catalyzes a substrate level phosphorylation of ADP using the high-energy substrate Phosphoenrolpyruvate(PEP)
55
In the absence of oxygen, what reaction occurs?
Fermentation
56
What is the function of lactate dehydrogenase in fermentation?
Oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
This prevents glycolysis from turning all NAD+ to NADH when turning pyruvate to lactate
57
In what circumstances is fermentation done in animal cells?
Typically done when oxygen is poor, heart attack, stroke or exercise
58
Describe fermentation in yeast cells
The conversion of pyruvate (3 carbon molecule) to ethanol and carbon dioxide (still replenishes NAD+)
59
What is the use of Dihydroxyacetone-P( DHAP)?
Used in hepatic and adipose tissue for triglycerides synthesis.
-Can be be converted to glyceraldehyde thex3-phosphate which can then be converted for the triglyceride backbones
60
How is DHAP formed in glycolysis?
Formed from fructose-1,6-bisphosphate by aldolase
61
What are the functions of 1,3-biphosphoglycerate (1,3-BPG) and Phosphoenrolglycerate(PEP) in glycolysis?
High-energy intermediates used to generate ATP by substrate level phosphorylation.
This is the only ATP gained in anaerobic respiration
62
What are the 3-irreversible enzymes of glycolysis?
- Glucokinase or Hexokinase
- PFK-1
- Pyruvate kinase
63
What is the importance of gluconeogenesis?
The liver uses gluconeogenesis to obtain new glucose molecules
64
Why does gluconeogenesis not use irreversible enzymes of glycolysis?
Gluconeogenesis is the reverse of glycolysis and therefore uses other enzymes aside from the irreversible enzymes of glycolysis
65
What is the net product of glycolysis in erythrocytes?
2 ATP per glucose
66
Describe the occurrences of adaption to high altitudes?
- Increased respiration
- Increased oxygen affinity for hemoglobin(initial)
- increased rate of glycolysis
- Increased (2,3 -Biphosphoglycerate in RBC over a 12-24 hour period)
- Normalized oxygen affinity for hemoglobin restored by the increased level of 2,3- BPG
- Increased hemoglobin(over days to weeks)
67
What step of glycolysis is different in Red blood cells than most other cells?
1,3-Biphosphoglycerate is converted to 2,3 Biphosphoglycerate by Biphosphoglycerate mutase
68
What are mutases?
Enzymes that move a a functional group from one place in a molecule to another
69
What is the effect of mutase on 1,3-bisphosphoglycerate ?
Moves the phosphate from the 1-position to the 2-position
2,3- BPG binds allosterically to the B-chains of the Hemoglobin A
70
How does 2,3- BPG affect oxygen dissociation (include knowledge of curve)
2,3-BPG decreases affinity for oxygen of HbA
This causes a rightward shift in the oxygen dissociation curve for HbA to allow unloading of oxygen in tissues but still allows for 10p% saturation in lungs
71
What may an abnormal increase in 2,3-BPG cause?
Oxygen-dissociation curve may shift so far to the right, 10l% saturation may nit exist in the lungs
72
What are the chemical changes that promote a rightward shift in the oxygen dissociation curve(Bohr effect)?
- High 2,3-BPG
- Low pH
- High proton concentration
- High pCO2
73
2,3-BPG does not bind well to fetal hemoglobin, why is this?
Fetal hemoglobin HbF has a higher affinity for oxygen the HbA
74
Why does HbF have a higher affinity for oxygen than HbA?
Allows trans placental passage of oxygen from mother to fetus
75
What is primary lactose intolerance?
Caused by hereditary deficiency of lactase
76
What is secondary lactose intolerance?
Due to gastrointestinal damage to intestinal lining wherever lactase is found
77
What are symptoms of lactose intolerance?
- Vomitting
- Bloating
- Explosive and watery diarrhea
- Cramps
- Dehydration
78
What causes the symptoms of lactose intolerance?
Due to bacterial fermentation of lactose, mixtures if methane, hydrogen and small organic acids are produced
This results in the movement of water into the intestinal lumen
79
Explain the metabolism of Galactose(part 1)
1. Lactose converted to galactose and glucose(by lactase) in the intestine
2. Galactose travels in blood to liver, brain and other tissues
3. In tissues, ATP and Galactokinase phosphorylates Galactose to Galactose-P
4. Galactose-1-P is converted to Glucose-P by UDP-Glc and uridyltransferase
80
Explain the galactose metabolism (part 2)
5. Glucose 1-P is converted to Glycogen and Glucose 6-p
| 6. Glucose 6-p may be converted to glucose or used in glycolysis
81
How does galactose arrive to the liver?
The hepatic portal veins
82
What are epimerases?
Enzymes that catalyze the conversion of one sugar epimer to another
83
What causes cataracts ?
Caused by the conversion of excess galactose in the blood to galactitol in the lens of the eye by aldose reductive
84
How is galacticol formed in the eye?
1. Lactose broken down into glucose and galactose by lactase
2. Galactose accumulates in the blood
3. In the lens, aldose reductase converts galactose into galactitol
85
How is galactose-1-phosphate converted to glucose-1-phosphate?
By galactose-1-phosphate uridyltransferase and an epimerase
86
What are effects of galactose-1-phosphatase uridyltransferase deficiency?
Causes galactosemia
As well as galactose-1-phosphate getting stuck intracellular LH in the liver, brain and other tissues
Not diffusing out
87
Genetic deficiencies if galactokinase or galactose-1-phosphate uridyltransferase lead to ___________
Galactosemia
88
Where can fructose be found?
In honey and sucrose(table sugar)
89
How can sucrose be converted to glucose and fructose?
Sucrose is hydrolyzed by the duodenal brush-border enzyme sucrase
Resulting in glucose and fructose
90
Explain the metabolism of fructose in the body
1. Fructose from sucrose, fruits and honey enter blood
2. Tissues except for kidney and liver, fructose phosphorylated by Hexokinase
3. Liver and kidney have fructokinase which phosphorylates fructose
91
Explain the metabolism of fructose in the body part 2
4. Fructose-1-P is converted to Glyceraldehyde and DHAP by Aldolase-B
5. Glyceraldehyde converted to Glyceraldehyde-3-P and Glyceraldehyde and DHAP used in glycolysis, gluconeogenesis and glycogenesis
92
How does liver trap fructose within cells?
Phosphorylates fructose via fructokinase
93
Why does a high- fructose drink supply a quick source of energy of aerobic and anaerobic cells?
Fructose metabolism provides dihydrodyacetonephosphate and glyceraldehyde which are downstream from the rate limiting enzyme PFK-1 of glycolysis
94
What happens to pyruvate from aerobic glycolysis?
Pyruvate enters the mitochondria and is converted to Acetyl CoA for entry to the citric acid cycle or to fatty acid synthesis of ATP is present
95
Different Pyruvate dehydrogenase in the liver and the nervous system
Pyruvate dehydrogenase is stimulated by insulin in the liver
Pyruvate dehydrogenase cannot be stimulated by insulin/hormones in the nervous system
96
Why is Pyruvate dehydrogenase not stimulated by hormones in the nervous system but stimulated by insulin in the liver?
High insulin levels signal a well-fed state, this indicates to the liver that should burn glucose for energy and shift fatty acid equilibrium to storage and production and not oxidation
97
The Pyruvate dehydrogenase (PDH)complex reaction is_____________ and thus___________
Irreversible
Acetyl CoA cannot be converted to Pyruvate or glucose
98
Describe the Pyruvate dehydrogenase complex reaction
1. Pyruvate reacts with NAD+, CoA and Pyruvate dehydrogenase and forms NADH, CO2 and Acetyl CoA
2. Acetyl CoA can be converted to fatty acids or Carbon dioxide and water for the citric acid
99
What are the possibilities of vitamin B1(thiamine) deficiency?
Beriberi- congestive heart failure or nerve damage
Wernicke Kirsakoff syndrome- difficulty walking, uncoordinated eye movements, confusion, memory disturbances
100
What are the consequences of giving glucose to a person with thiamine deficiency?
Can lead to severe acidosis and other metabolic derangements because Pyruvate cannot be converted to Acetyl CoA without the vitamin
101
What happens when cofactors and coenzymes are in insufficient amounts?
Metabolic derrangements
102
What inhibits Pyruvate dehydrogenase?
It’s product, Acetyl CoA
103
What does the build up of Acetyl CoA lead to?
Acetyl CoA build up leads to a shift in metabolism
This prevents Pyruvate from being converted to Acetyl CoA(to enter the citric acid cycle) but rather to oxaloacetate(to enter gluconeogenesis )
104
Where does glycogen synthesis and breakdown usually occur?
Mainly in the liver and skeletal muscle
105
Describe a glycogen granule
Each granule has a core protein with poly glucose chains radiating outward to form a sphere
106
How does branching affect glycogen granules?
Glycogen granules composed of entirely linear chains have the highest density of glucose near the core.
If the chains are branched, the glucose density is highest at the periphery of the granule, allowing more rapid release of glucose on demand
107
How do glycogen roles differ in skeletal muscle and liver?
Skeletal muscle- glycogen used to produce glucose for muscle during exercise
Liver- glycogen is broken down to maintain a constant blood level
108
What is glycogenesis?
Synthesis of glycogen granules
109
Explain the addition of glucose to glycogen
1. Glucose is converted to glucose-6-P
2. Glucose-6-P is converted to glucose-1-P
3. Glucose-1-P interacts with Uridine triphosphate (UTP) to form UDP-glucose and pyrophosphate(PPi)
4. UDP-Glucose reacts with glycogen synthase and a branching enzyme forms UDP and glucose is added to glycogen
110
What is glycogen synthase?
The rate-limiting enzyme of glycogen synthesis and forms the a-1,4 glycosidic bond found in the linear chains of glycogen
111
How is glycogen synthase stimulated?
Glycogen synthase is stimulated by glucose-6-phosphate and insulin
112
How is glycogen synthase inhibited?
Inhibited by epinephrine and glucagon through a protein kinase cascade that phosphorylates and inactivated the enzyme
113
What is the glycogen branching enzyme?
Glycosyl a-1,4: a-1,6 transferase
114
What is the function of the glycogen branching enzyme?
Responsible for for introducing a-1,6-linked branches to the glycogen granules
115
How does the glycogen branching enzyme add a-1,6 bonds to glycogen?
- Branching enzyme hydrolyzed an a-1,4 bond
- Branching enzyme transfers oligoglucose unit and attaches it with an a-1,6 bond to make a branch
- Glycogen synthase extends both branches
116
How does a hydrolases differ from phosphorylase?
Phosphorylase uses the an inorganic phosphate instead of water to break bonds
117
What enzyme releases glucose-1-phosphate in glycogenolysis?
Glycogen phosphorylase -the rate limiting enzyme of glycogenolysis
118
How is glycogen phosphorylase is activated in the liver?
By glucagon so glucose can be provided by the rest of the body
119
How is glycogen phosphorylase activated in skeletal muscle?
Activated by AMP and epinephrine which signals that muscle requires more glucose
120
What inhibits glycogen phosphorylase/glycogenolysis?
AMP
121
Explain the process of the debranching enzyme producing free glucose
1. Breaks an a-1,4 bond adjacent to the branch point and small oligoglucose chain that is released to the exposed end of the other chain
2. Forms a new a-1,4 bond
3. Hydrolyzes the a-1,6 bond releasing the single residue at the branch point as free glucose
122
What are the enzymes that make up the debranching enzyme and their function?
1. a-1,4; a-1,4 transferase moves the terminal end of a glycogen chain to the branch point
2. a-1,6 glucosidase removes the glucose monomer actually present at the branch point
123
Give the 4 steps for the overall functional the debranching enzyme
1. Glycogen phosphorylase releases glucose 1-P from the periphery of the granule until it encounters the first branch point
2. Debranching enzyme hydrolyzes the a-1,4 bond nearest the branching point
3. Debranching enzyme transfers the oligoglucose unit to the end of another chain
4. Hydrolyzes the a-1,6 bond, releasing the single glucose from the former branch
124
What are isoforms?
Different versions of the same proteins
125
What are glycogen storage diseases?
Deficiencies of different isoforms of the enzymes in the liver and muscle or lack glycogen in one or more tissues
126
What is von Gierke’s disease?
A defect in glucose-6-phosphatase
127
Explain the effects of von Gierke’s disease?
Because glucose-6-phosphatase is the last step of gluconeogenesis the whole process is affected
128
What are the effect of von Gierke’s disease?
1. Periods of extremely low blood sugar between meals
| 2. Glucose-6-phosphate in liver cells causes liver cells to enlarged and damage over time
129
What are glucogenic amino acids?
Amino acids that can be converted to intermediates that feed into gluconeogenesis
130
What are ketogenic amino acids?
Amino acids can be converted into ketone bodies, which can be used as an alternative fuel, particularly during periods of prolonged starvation
131
What amino acids are NOT Glucogenic amino acids?
Leucine and lysine
