Carbohydrate Digestion & Glycolysis Flashcards
1
Q
What are the 4 major digestible carbohydrates?
A
Starches (amylose and amylopectin)
Sucrose
Lactose
2
Q
What types of carbohydrates do dietary enzymes break down?
A
Monosaccharides. Enzymes are specific for how they are linked together also
3
Q
Major carbohydrates are broken down into _____ which enter the blood
A
monosaccharides
4
Q
List the 3 major monosaccharides
A
a-D-Glucose
a-D-Galactose (epimer of glucose)
a-D-Fructose (ketose hexose, sweetest)
5
Q
Which monosaccharides make sucrose? How are they linked?
A
Fructose and glucose
a-1,2 link
6
Q
Which monosaccharides make lactose (major sugar of milk)? How are they linked?
A
Galactose and glucose
b-1,4 link
7
Q
Starches are polymers of?
A
glucose
8
Q
What are the types of starches?
A
Amylose
Amylopectin
9
Q
How are the monosaccharides linked in amylose
A
a-1,4
10
Q
How are the monosaccharides linked in Amylopectin?
A
a-1,4 amylose chains (linear) linked by a-1,6 (branched)
11
Q
What kind of linkage do lactase hydrolyze?
A
b-1,4 (the link in lactase)
12
Q
What kind of linkage do sucrase hydrolyze?
A
a-1,2
13
Q
What kind of linkage do amylase hydrolyze?
A
a,1-4
14
Q
What kind of linkage do isomaltase hydrolyze?
A
a-1,6
15
Q
What two enzymes do amylopectin needs in order to be broken down?
A
amylase & isomaltase
16
Q
What is one indigestible carbohydrate?
A
Fiber
17
Q
What enzyme is there in the mouth and what does it break down?
A
Salivary amylase.
Starch into a-dextrin
18
Q
What enzyme is there in the pancreas and what does it break down?
A
Pancreatic amylase
Secreted into the small intestine for further degradation of a-dextrin and trisaccharide
19
Q
What is the significance of brush border in the small intestine?
A
More surface area to break down food we eat
20
Q
What enzyme is there in the small intestine and what does it break down?
A
Disaccharidases (sucrase, lactase, maltase, isomaltase)
Degrades disaccharides into monosaccharides
21
Q
What happens to monosaccharides after the small intestine?
A
Transported to intestinal epithelial cells
22
Q
How do you tell the difference between amylose and amylopectin
A
Amylopectin is branched
23
Q
What is the difference between the two types of fiber?
A
Soluble fiber - dissolves in water and forms gel substance in the stomach. Broken down by bacteria in the large intestine (found in oats, beans flesh of dry fruits)
Insoluble fiber - does not dissolve in water. Passes through digestive system intact (found in flour nuts, beans)
24
Q
Benefits of fiber
A
Reduces risk of colon cancer and cardiovascular disease
Soluble fiber - slows absorption of food, lowers glycemic index, lowers cholesterol
Insoluble fiber - increases frequency of bowel movements
25
Which carbohydrate is the most common?
cellulose
it is insoluble fiber
Polysaccharide of glucosyl residues (b-1,4)
We cant break it down bc we do not have enzyme for linkage
26
How does water soluble fiber lower cholesterol
Some bacteria in the colon that break down water soluble fiber, also breaks down cholesterol
Compound class is b-glucans - a nutrient for bacteria that can break down cholesterol
27
What is lactose intolerance
The lack of the enzyme that breaks down lactose
- causes gas and diarrhea when a large amount of milk is consumed (bc having all that sugar in the colon draws in water)
- Lactic acid produced by anaerobic bacteria draws water by osmosis into the intestinal lumen to produce diarrhea
- Bacterial fermentation also produces hydrogen and methane gas
28
How is glucose transported from diet into tissues
First we need to transport it from the lumen of small intestine to epithelial cells
Small intestine:
1. From diet to lumen
- SGLT2 - secondary transport (glucose and galactose)
- GLUTT5 passive transport (fructose)
2. From lumen into blood
- GLUT2 passive transport (fructose, glucose, galactose)
Into Tissues:
- GLUT passive transport system
29
What classification does SGLT (sodium-linked glucose transporter) belong to and which tissue is it located inb
secondary active transport
| small intestine
30
What classification does GLUT2 belong to and which tissue is it found?
Passive
| Liver, pancreas, small intestine and kidney
31
What classification does GLUT5 belong to and which tissue is it found?
Passive
| small intestine
32
What is the main role of SGLT1
Promotes glucose and galactose absorption coupled with Na+ transport
33
Why is SGLT1 a secondary active transporter?
active -moves monosaccharides into the small intestine epithelial cells against their concentration gradient
secondary - it uses the sodium gradient generated by a primary active transporter (Na/K ATPase -uses energy of ATP hydrolysis to pump NA out of cell and K into cell)
SGLT couples the favorable gradient for sodium to go into the cell with the accumulation of glucose/galactose
34
Regarding SGLT1, what does the rate of glucose transport depend on
[Na+] and [glucose]
Glucose will facilitate Na+ absorption and chloride always follows sodium, thats a way of getting water into the small intestine
35
In the intestinal lumen of the small intestine _____ couples glucose/galactose uptake with _______
SGLT1, Na+
36
In the intestinal lumen of the small intestine _____ transfers fructose into the intestine small epithelial
GLUT5
37
______ facilitates transport of glucose, galactose and fructose from the epithelial cell to the blood (downhill efflux to the blood)
GLUT2
38
Describe a clinical implication of SGLT1
Oral Rehydration therapy (ORT) for treatment of acute diarrhea
- glucose stimulates sodium uptake across brush border membrane of the small intestine. Two Na+ for every molecule of glucose. Water follows
it stimulates SGLT which promotes water reabsorption because of the sodium being absorbed
39
Which is the only GLUT stimulated directly by influence
GLUT4
| in muscle
40
GLUT1 is _____ and is found in the ______
passive, RBC blood brain barrier
41
GLUT2 is ____ and is found in the ______
passive, liver, pancreas, small intestine, kidney
42
GLUT3 is _____ and is found in the ______
passive,neurons
43
GLUT4 is _____ and is found in the ______. It is stimulated by ______
passive,
muscle, adipose
insulin
44
Which GLUT has a very high Kt
GLUT2
45
For transporters, rate of transportation depends on
concentration of substrate (solute that they transport)
ie Kt is equivalent to km
46
What does a high Kt mean for transporters
Glucose will be below that (the Kt) and rate of transport will be very responsive to any increase/decrease in glucose. Increase when glucose is high and decrease when glucose is low
47
How insulin stimulates glucose transport in adipose and muscle: Fasting state
1. Low blood glucose and low insulin
- GLUT4 transporters are sequestered in membrane bound vesicles so they cant be involved in taking up glucose from the plasma membrane
- Therefore since there isn't many GLUT4 at the plasma membrane to take up glucose, the cell takes up less glucose
48
How insulin stimulates glucose transport in adipose and muscle: Fed state
High blood glucose and high insulin
- Insulin stimulates insertion of vesicles containing GLUT4 into the plasma membrane
- More GLUT4 in the plasma membrane of muscle cell, therefore the cell can take up a lot of glucose
49
How is glucose and galactose transported to the lumen
by secondary active transport using the SGLT1
50
How is fructose transported to the lumen?
by passive transport by the GLUT5
51
How is fructose glucose and galactose transported into the blood?
by passive transport via GLUT2
52
How monosaccharides transported to the tissue?
by GLUT passive transport
53
What is glycolysis?
- The enzymatic breakdown of glucose
- Can aerobic or anaerobic
- Can result in the production of ATP
- glycolysis are located in the cytoplasm
- also provides substrates for biosynthetic pathway (lipids, AA)
54
What are the 2 phases of glycolysis?
- Preparatory phase
| - Payoff phase
55
What s the preparatory phase of glycolysis?
phosphorylation of glucose and its conversion to glyceraldehyde 3-phosphate
2 ADP consumed
56
What is the payoff phase of glycolysis?
Oxidative conversion of glyceraldehyde 3-phosphate to pyruvate coupled with formation of ATP and NADH
4 ATP formed
2 NADH
Endpoint pyruvate
57
What are the key enzymes in the glycolytic pathway?
Preparatory phase:
1. Hexokinase/glucokinase - Step 1
2. Phosphofructokinase (PFK-1) - Step 3
3. Aldolase - Step 4
Payoff phase:
1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) - Step 6
2. Phosphoglycerate kinas - Step 7
3. Pyruvate kinase - Step 8
58
What are the enzyme regulated steps in the glycolytic pathway?
Preparatory phase:
1. Hexokinase/Glucokinase
2. Phosphofructokinase (PFK-1)
Payoff phase:
1. Pyruvate kinase
59
What step in the glycolytic pathway is hexokinase/glucokinase?
What does it do?
Step 1
| Phosphorylates glucose, ATP consumed
60
What step in the glycolytic pathway is phosphofructokinase (PFK-1)?
What does it do?
Step 3
| Phosphorylates fructose-6-phosphate, ATP consumed
61
What step in the glycolytic pathway is aldolase?
| What does it do?
Step 4
| Cleaves 6C sugar into two 3C sugars
62
What step in the glycolytic pathway is glyceraldehyde 3-phosphate dehydrogenase (GAPDH)?
What does it do?
Step 6
| Reduces NAD+ to NADH (requires NAD+)
63
What step in the glycolytic pathway is phosphoglycerate kinase?
Step 7
| 1st ATP forming reaction (substrate level phosphorylation)
64
What step in the glycolytic pathway is pyruvate kinase?
Step 8
| 2nd ATP forming reaction (substrate level phosphorylation)
65
Describe step 1 of the glycolytic pathway?
- Hexokinase (glucokinase in the liver) glucose to G6P
- Phosphorylation prevents efflux of glucose from cell
- G6P is a precursor for every pathway that uses glucose
- Highly exergonic step that consumes ATP
- Energy from ATP is conserved in phosphodiester bond
- Enzyme regulated step
66
What is the Km of hexokinase and glucokinase respectively?
~10mM and 0.1mM
67
Which is inhibited by G6P, hexokinase or glucokinase?
Hexokinase
68
Describe step 3 of the glycolytic pathway
- PFK-1 Allosteric enzyme, highly regulated, committed step in glycolysis
- Phosphorylation of F6P to F-1,6-BP and ADP
- 2nd ATP investment
- Delta G = -22kJ/mol
69
What is the substrate for the 1st substrate-level phosphorylation step?
1,3-BPG
It is high energy
Overall reaction is reversible
70
What is the substrate for the 2nd substrate-level phosphorylation step?
PEP
liver pyruvate kinase is an allosteric enzyme
pyruvate is the endpoint of aerobic glycolysis
71
What is the fate of pyruvate in aerobic glycolysis?
- Pyruvate enters mitochondria and is converted to Acetyl CoA
- THE CAC oxidized Acetyl CoA to CO2 and generates NADH
- The ETC oxidizes NADH and reduces O2 to H2O
- NADH from glycolysis enters via shuttle system and enters ETC
72
What is the fate of pyruvate in anaerobic glycolysis?
- pyruvate converted to lactate by lactate dehydrogenase
- occurs in RBC and tissue with low O2 supply
- NADH is oxidized to NAD+ by reducing pyruvate to lactate which allows glycolysis to continue
73
What can happen in excessive anaerobic glycolysis?
```
lactic acidosis
B/c lactate has a carboxylic acid group
Can happen during:
- intense exercise
- heart attack
- severe anemia
- large tumors
```
74
Describe the two mechanisms by which oxidation of NADH can occur?
1. Aerobic glycolysis:
- NADH enters mitochondria via reversible shuttle system and is oxidized by the ETC
HOWEVER
IMM is impermeable to NADH/NAD+ and that's were the term shuttle system comes into play
2. Anaerobic glycolysis:
NADH is oxidized by lactate dehydrogenase
75
First shuttle that gets electrons from NADH from cytosol to IMM:
glycerol 3-phosphate dehydrogenase
- It oxidizes NADH to produces glycerol-3-P
- Isozyme oxidizes glycerol-3-P to generate FADH2
- Oxidized FADH2 to generate UQH2 (only 2 electrons are shuttled bc FADH2 is tightly bound to glycerol 3-phosphate dehydrogenase)
- UQH2 enters ETC at complex 3
- Complex 3 = 1.5 ATP/NADH
76
second shuttle that gets electrons from NADH from cytosol to IMM:
How does malate-aspartate shuttle works?
Big picture: reversible shuttles NADH from cytosol to NADH in mitochondria
- involves isozymes in cytosol and matrix and transporters in the IMM
- NADH in cytosol gets oxidized to NAD+ and produces malate
- Malate can be imported to mitochondria by transporter
- in the matrix, another malate dehydrogenase oxidizes malate and produces NADH
- NADH enters the ETC at complex 1 (get all the possible energy)
- Carbons that came into cell leaves to the cytosol as aspartate
77
What is the cori cycle
- Pyruvate in the liver is converted to glucose via gluconeogenesis
- Glucose goes to the RBC and intensely exercising muscles.
- Lactate is generated via glycolysis because there is no mitochondria for aerobic glycolysis
- Lactate is released to the blood
- Liver takes up lactate and converts it to pyruvate
78
Relationship of glycolysis to other pathways
slide 44
79
Hormonal regulation of glycolysis in the liver?
- insulin favors glycolysis in the liver
| - glucagon, epinephrine and glucocorticoids inhibit glycolysis in the liver
80
What are the major sites of regulation in the glycolytic pathway?
1. Hexokinase
- muscle (G6P inhibits)
- liver glucokinase (stimulated by insulin and glucose)
2. PFK-1
ATP inhibits
F-2,6-BP, AMP activates
3. Pyruvate kinase (liver only)
ATP inhibits
F-1,6,-BP activates
81
Describe glucokinase regulation
- After a meal, blood glucose levels rise
- Rate of entry into hepatocytes increase through GLUT2
- High glucose in the cytosol. GK is a glucose sensor so increased GK activity in the cytosol
- Increased G-6-P increases flux through glycolysis
82
How does F-2,6-BP regulate glycolysis
Its level in the cell mirrors/favors glycolysis
83
How does insulin influence F-2,6-BP?
| How does glucagon influence F-2,6-BP?
Increases
| Decreases
84
Describe regulation of glycolysis in the liver through pyruvate kinase
1. F-1,6-BP allosterically activates Pyruvate Kinase
2. ATP allosterically inhibits pyruvate kinase
3. Insulin promotes glycolysis by dephosphorylation and it is going to cause the pyruvate kinase to be active
4. cAMP phosphorylated by cAMP depended kinase which makes it inactive
85
Describe pyruvate kinase deficiency
- Most common defect of glycolytic enzymes
- expressed in erythrocytes (all tissue)
- leads to decreases ATP production
- Hemolytic anemia: premature death and lysis of red blood cells
86
Liver and glucose relationship
You only want liver cell using glucose for energy when there is a lot of glucose around.
liver's job when we're not eating is to put out glucose. We don't want to be wasting the glucose on itself
87
How does insulin affect pyruvate kinase and therefore glycolysis
- insulin causes removal of phosphate
- phosphate makes pyruvate kinase inactive'
- if phosphate is removed, it makes it active
- more active pyruvate kinase = more glycolysis
88
How does glucagon and epinephrine affect pyruvate kinase and therefore glycolysis
- glucagon and epinephrine stimulate phosphorylation of pyruvate kinase and slows the enzyme down
- Therefore they slow down glycolysis
