Lecture 2: CHO transport and metabolism 1 Flashcards
1
Q
What is called the energy currency of the body
A
adenosine triphosphate (ATP)
2
Q
How is energy derived from the oxidation of carbohydrates used in the production of energy?
A
Used to convert adenosine diphosphate (ADP) to ATP
3
Q
ATP is present in which cell types(s)?
A
All cells
4
Q
ATP production is a cycle. What do we mean by this?
A
ATP is continous made and broken down
ATP ⇔ ADP + Pi
5
Q
How long does quantities of ATP present in the tissues sufficient for?
A
•Quantities of ATP present in tissues are sufficient for a few seconds only unless replenished.
6
Q
Name the 3 mechanisms used by the cells to replenish ATP stores?
A
- Creatine phosphate (in muscle but only short term)
- Anaerobic metablism of carbohydrate to lactate.
- Aerobic metabolism of carbohydrate, fat and/or protein (in mitochondria)
7
Q
Which mechanism will RBC use to replenish ATP stores?
A
Anaerobic metabolism only.
Requires mitchondria in order to undertake aerobic metabolism (which is lacking in RBCs)
8
Q
Why must blood glucose levels be regulated?
A
So blood sugar is available in all cells of the body, including those that only utilise anaerobic metabolism e.g. RBCs.
These anaerobic cells depend on carbohydrate being present to allow their ATP stores to be replenished (cannot replenish using fat or protein)
9
Q
Which macronutrients must be used for aerobic metabolsm to replenish the ATP store in cells?
A
Carbohydrate, protein, and fat
10
Q
Which macronutrients must be used for anaerobic metabolsm to replenish the ATP store in cells?
A
Carbohydrate
11
Q
Name the three classes of carbohydrates?
A
- Polysaccharides
- Dissachrides
- Monosaccharides
All found in the diet of humans
12
Q
Name the two types of polysacchrides found in our diet? How do they differ in their metabolism
A
- Starch (broken down into glucose)
- Cellulose (cannot be digested)
13
Q
Why can’t we digest cellulose?
A
Starch contains beta-1,4 glycosidic bonds
Enzymes capable of hydrolyzing cellulose (cleaving the beta-1,4 glycosidic bonds) are not secreted in the human digestive tract
Consequently, cellulose cannot be considered a food for humans.
14
Q
Starch is hydrolyzed into which diaccharide?
A
Maltose
15
Q
Name the 3 types of dissacharides?
A
- Maltose
- Sucrose
- Lactose
16
Q
Maltose is hydrolyzed into which monosacchardies?
A
Glucose + Glucose
17
Q
Sucrose is hydrolyzed into which monosacchardies?
A
Glucose + Fructose
18
Q
Lactose is hydrolyzed into which monosacchardies?
A
Glucose + Galatase
19
Q
Which class of carbohydrate is the final product of carbohydrate metabolism?
A
Monosaccharides
20
Q
Monosaccharides are all water ____ and are absorbed immediately into which vessel?
A
Water soluble.
Absorb into the portal vein.
21
Q
Describe the types of carbohydrates in the diet
A
3 classes of carbohydrates
Polysaccharides
- Starch
- Cellulose **not digested by humans**
Dissacharides
- Maltose
- Sucrose
- Lactose
Monosaccharides
- Glucose
- Fructose
22
Q
Fill in the blanks
A
23
Q
D part of D-glucose refers to what?
A
to the way solution of glucose will rotate plane of polarised light to the right (dextro).
24
Q
alpha/beta part of alpha-D-glucose or beta-D-glucose refers to what?
A
refers to whether –OH group below (alpha) or above (beta) C1 atom.
25
Monosaccharides in disaccharides and polysaccharides are held together by which kind of bond
Glycosidic bonds
26
Which glycosidic bond holds together the monosaccharides fructose and glucose (in the disaccharide surcose, table sugar)?
alpha (1→2)Glycosidic bond
27
Which glycosidic bond holds together the monosaccharides in the polysaccharide starch?
alpha (1→4)Glycosidic bond
28
Digestion of carbohydrate occurs in which sites of the Gi tract?
* Begins in the **mouth**- saliva
* Final part in the **small** **intestine** - pancreatic secretions and intestinal epithelial enzymes
29
Describe the process of carbohydrate digestion in the mouth?
* When food is chewed, it is mixed with saliva, which contains the digestive enzyme salivary α-amylase secreted mainly by the parotid glands.
* α-amylase hydrolyzes starch into the disaccharide maltose.
* However, the food remains in the mouth only a short time, so probably not more than 5 percent of all the starches will have become hydrolyzed by the time the food is swallowed.
* Does not digest the disaccharides.
* Once in the stomach, activity of the salivary amylase is then blocked by acid of the gastric secretions because the amylase is inactive once the pH of the medium falls below about 4.0.
30
Describe the process of carbohydrate digestion in the small intestine?
_Pancreatic amylase:_
* Pancreatic secretion contains a large quantity of α-amylase that is almost identical in its function to the salivary α-amylase but is several times as powerful
* Completes the digestion of starch into maltose
_Intestinal epithelial enzymes:_
* The the enterocytes covering the intestinal microvilli brush border contain four enzymes (lactase, sucrase, maltase, and α-dextrinase)
* These enzymes are capable of splitting the disaccharides lactose, sucrose, and maltose, plus other small glucose polymers, into their constituent monosaccharides.
* FInal product of carbohydrate digestion is monosaccharides
31
all the carbohydrates in food are absorbed in which form?
Absorb as monosaccharides
32
the most abundant of the absorbed monosaccharides is?
Glucose
accounts for more than 80 percent of the carbohydrate absorbed
33
Give examples of how the properties of the food influence the digestibility of starch.
* The digestibility of starch varies with properties of food i.e. some starches are slowly digested.
* Some starches are very dense and are slowly digested as this tightly packed structure reduces the number of active sites available for enzyme activity.
* Dietary fibre present can slow digestion and the gut contents become more viscous.
* Foods with a high fat content may have delayed gastric emptying and because a lot of the digestion of CHO occurs in the SI, this delays digestion.
34
Describe the term "glycaemic index"?
* GI is a rating system for foods containing carbohydrates. It shows how quickly each food affects your blood glucose level when that food is eaten on its own
* _high GI_ - foods are quickly digested and absorbed so affects blood glucose levels quickly.
* _Low GI_- foods are slowly digested and absorbed so affects blood glucose levels slowly.
35
Give examples of carbohydrates who have a high glucaemic index
**Cereals** e.g. wholemeal bread and cornflakes
36
Give examples of carbohydrates who have a low glucaemic index
Beans and lentils e.g. soya beans, kidney beans and lentils
37
Glucose is ____ form of carbohydrates in humans
Glycogen is ____ form of carbohydrate in humans
A) Transport
B) Storage
38
Why is the brain dependent on the constant supply of glucose as these cells are capable of aerobic metabolism (as they contain mitochondria)?
* Brain contains lots of mitochondria, so capable of aerobic metabolism
* However the other forms, lipids and proteins, cannot past easily across the BBB.
* Therefore glucose is the fuel as others cannot gain entry into the brain.
39
Why are the erythrocytes dependent on the constant supply of glucose
As they do not contain mitochondria therefore unable to do aerobic metabolism.
Therefore can only do anaerobic metabolism, which glucose is the only supply for.
40
Plasma glucose concentration is tightly regulated. Which range of concentrations are maintained by the body?
between concentrations of 4-5 mM (in fasted state).
Can raise to 8-12 mM after a meal.
41
What are the two pricinipal hormone regulators for glucose homeostasis?
Insulin and glucagon
42
Which hormone acts in the excess carbohydrate state?
A) Insulin
B) Glucagon
A) Insulin
43
Which hormone acts in the fasted carbohydrate state?
A) Insulin
B) Glucagon
B) Glucagon
44
Insulin reduces blood sugar in two ways. What are these two ways?
* It causes cells in the body to absorb glucose from the blood and use it as fuel
* Tt causes muscle and liver cells to absorb glucose from the blood and store it as glycogen
45
Define gluconeogenesis
Process in which glucose is synthesised by the liver
The liver converts proteins and fats into glucose.
46
Define glycogenolysis
Process in which glycogen stores are broken down into glucose.
Occurs in the liver only
Even though glycogen stores are found in the muscle cells, these are not reversible.
47
Define ketogenesis
* Ketogenesis occurs when there is insufficient glucose supply and glycogens stores are exhausted, such as in prolonged fasting.
* The liver takes fatty acids and converts them to ketones.
* Ketones are water soluble fatty acids that can be used as fuel, the can cross the blood brain barrier and be used by the brain.
* Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on very low carbohydrate, high fat diets.
48
Why can't glucose simply diffuse into the cells
Glucose must be transported through the cell membrane into the cellular cytoplasm because the maximum molecular weight of particles that can diffuse readily is about 100, and glucose has a molecular weight of 180.
49
Name the two classes of glucose transporters, which are involved in the absorption of glucose into the enterocytes
1. GLUT (1 -\> 5)
2. SGLT 1 and 2
50
Which class of glucose transporter transports glucose down its concentration gradient by facilitated diffusion
GLUT
51
Which class of glucose transporter transports glucose against its concentration gradient by active transport
SGLT 1 and 2
52
Where are SGLT 1 and 2 transporters located in the body
* The intestinal mucosa (enterocytes) of the small intestine (SGLT1)
* The proximal tubule of the nephron (SGLT1 + 2)
53
Describe the mode of mechanism for SGLT 1 and 2
* Sodium-glucose linked transporter (SGLT 1 and 2)
* Co-transports one molecule of glucose or galactose along with sodium ions (NOT FRUCTOSE)
* Sodium conc inside the cell is low (so sodium travels down its concentration gradient). As the sodium enters the cell, it is actively transported out into the interstitial fluid (via Na:K ATPase).
* Glucose is transported against its concentration gradient using the energy provided by the cotransport of sodium.
54
Why is it important to have SGLT 1 + 2 transporters present in the intestinal and kidneys
Required in intestine to absorb from gut lumen
Required in the kidney, to reabsorb from filtrate.
In these areas, the initial concentration of glucose in the lumen will be greater than the cells. However, as more and more glucose is absorbed the concentration of glucose will be lower in the lumen. Therefore, requires SGLT to actively absorb the rest of the glucose so we get all the glucose out of a meal
55
How many GLUT transporters are there?
14 (GLUT 1 to 14)
GLUT 1 to 5 is . well characterised in glucose transportion
56
Describe the mode of mechanism for GLUT-1 transporters?
* Found in all cells of the body.
* Transports glucose (high affinity) and galactose
* NOT FRUCTOSE
* Facilitative transport of glucose into the cell
57
Which GLUT transporter is the main transporter in the liver and in beta cells in the Islet of Langerhans?
GLUT 2
58
Describe the mode of mechanism for GLUT-2 transporters?
* Main transporter in the liver and in the beta cells
* Located in the liver, beta cells, small intestine and kidneys
* Function is to transport glucose, galactose and fructose.
* Low affinity, high capacity glucose transporter
59
Describe the mode of mechanism for GLUT-3 transporter
* Similar to glut-1 but in the brain.
* Transports glucose (high affinity) and galactose
* Does not transport fructose
* They are the primary glucose transporters for neurones
60
Which GLUT transporter is the primary glucose transporters for neurones
GLUT-3
61
Describe the mode of mechanism for GLUT-4 transporters?
* Insulin sensitive transporter- it is highly responsive to insulin. i.e. after a meal this is activated massively.
* **Present in skeletal and cardiac muscle, and adipose tissue**
* In adipose it stores excess glucose as triglyceride.
* **GLUT 4 is not found in the liver.**
62
Describe the mode of mechanism for GLUT-5 transporter?
* Located in the small intestine and sperm.
* Function is to transport fructose only
* **does not transport glucose or galactose**
63
Insulin stimulates action of ___ cells and inhibits ____ cells in the Islets of Langerhan
A) Beta
B) Alpha
64
Somatostatin leads to inhibition of both ___ and ___ cells in the Islets of Langerhan
A) Alpha
B) Beta
65
66
Describe the mechanism in which GLUT4 is responsive to physical activity?
* In muscle, GLUT4 translocates in response to physical activity/exercise (independent of insulin)
* Results in increase entry of glucose into the cells- which is used in ATP production
67
What are the possible fates for a glucose once inside a cell?
All pathways require phosphorylation of glucose to glucose-6-
phosphate as first step
* Used in the production of ATP
* Glycogenesis
* Stored as glycogen (in muscle and liver cells)
* Storage as lipids in adipocytes
* Synthesis of sugars for RNA/DNA
68
What must happen to the glucose once it gets into the cell, independent on its fate?
Phosphorylation of glucose to glucose-6-phosphate must happen once itself the cell
69
Which enzymes causes the phosphorylation of glucose into glucose-6-phosphate
* Glucokinase (aka Hexokinase 4)
* Hexokinase 1 to 3
70
What is the differences between Glucokinase and Hexokinase (1 to 3)?
**_Glucokinase_**
* Expressed only on beta and liver cells
* Low affinity for glucose- therefore takes longer to be saturated so can respond to even high levels of glucose.
* The enzyme synthesis is regulated
**_Hexokinase 1, 2, 3_**
* Expressed in all tissue except beta and liver cells
* High affinity for glucose- saturated very quickly at low concentrations of glucose
* Is inhibited by G6P (negative feedback)- cell saying it has enough
71
Glucokinase is expressed in which cells?
Beta cell in the Islet of Langerhans
Hepatic cells
72
Hexokinase 1,2 and 3 are expressed in which cells?
All cells except beta cells and hepatocytes
73
Glucokinase has a ___ affinity for glucose
Low
74
Hexokinase has a ___ affinity for glucose
High
75
Hexokinase enzyme is inhibited by what?
G6P
Negative feedback
76
Fill in the blanks for this diagram that shows the affinity each hexokinase has for glucose
77
Define the term glycolysis?
It is the process of breakdown glucose into ATP
78
Where does glycolysis occur
In the cytoplasm of all cells
79
What are the net gain products of glycolysis?
2 Pyruvate (goes to TCA cycle)
2 ATP (generates 4 but uses 2 in the initial steps)
2 NADH
4 H+ (which is excreted)
80
At what point in glycolysis is known as the "irreversible stage"
When fructose-6-phosphate is converted to Fructose-1,6-biphosphate
81
The initial stages of glucolysis ____ 2 ATP
Uses
82
Phosphofructokinase converts fructose-6-phosphate into fructose-1,6-bisphosphate.
What inhibits its action
PFK activity is highly regulated
Inhibited by downstream products e.g. ATP, citrate.
It decides the fate of the glucose as pathways are inhibited by their product e.g. if cell has enough ATP the ATP will inhibit the PFK activity therefore the glucose fate will not be to form ATP but will become something else
83
Which enzyme activity determines the fate of glucose
Phosphofructokinase
84
NADH must be used so that NAD+ is replenished. What happens to NADH under anaerobic conditions?
Under anaerobic (without oxygen) conditions get lactate formation (no further ATP produced)
85
NADH must be used so that NAD+ is replenished. What happens to NADH under aerobic conditions?
Under aerobic (with oxygen) conditions, NADH can be used to make more ATP in mitochondria (TCA and electron transport chain)
86
Describe the metabolsm of fructose
Fructose is metabolised to intermediates of glycolysis, which then enters the glycolysis chain of events. Forming ATP.
* Fructose is converted to Fructose-1-phosphate (F1P) by fructokinase
* F1P is converted into DHAP and Glyceraldehyde-3-phosphate
* DHAP and Glyceraldehyde 3-phosphate are intermediates of glycolysis
87
Describe the metabolsm of galactose?
Galactose is metabolised to Glucose-1-phosphate and then to G6P, which then enters the glycolysis chain of events. Forming ATP.
88
What happens to pyruvate after it is formed from glycolysis (under anaerobic conditions)
Pyruvate is converted to lactate by lactate dehydrogenase.
Uses the NADH (therefore replenishing NAD+).
89
What is the net profite of ATP from metabolising glucose under anaerobic conditions
2 ATP
90
What happens to pyruvate after it is formed from glycolysis (under aerobic conditions)
* Pyruvate is converted to acetyl-coA.
* Occurs in the mitochondria by pyruvate dehydrogenase
* Requires coenzyme A and vitamins as co-factors (such as thiamine)
* Acetyl-coA enters the TCA cycle.
* Product is acetyl coA, CO2, NADH and H+
91
What is the net profite of ATP from metabolising glucose under aerobic conditions
36 ATP
However rarely occurs are the mitochondria is not a perfect system
92
For every molecule of NADH, how much ATP can be produced from it
1 : 3
93
For every molecule of FADH2, how much ATP can be produced from it
1 : 2
94
For every molecule of GTP, how much ATP can be produced from it
1 : 1
