Session 4 Flashcards
(168 cards)
1
Q
Name some cells/tissues that have an absolute requirement for glucose (4)
A
Red blood cells
Neutrophils
Innermost cells of kidney medulla
Lens of the eye
2
Q
What are some symptoms of hypoglycaemia?
A
Confusion, weakness, nausea, muscle cramps, brain damage, coma, death
3
Q
Hypoglycaemia is generally considered as a blood sugar level below…
A
4 mM/L
4
Q
Glycogen is a polymer of _________
In what form is glycogen stored?
A
Glucose
As granules
5
Q
What are two types of glycogen found in the body?
A
Muscle glycogen
Liver glycogen
6
Q
How is muscle glycogen and liver glycogen distinguished from each other?
A
Muscle glycogen - found as either intra- or intermyofibrillar granules
Liver glycogen - found as granules within hepatocytes
7
Q
Which parts of the body use liver glycogen stores?
A
The whole body calls upon the liver glycogen stores affecting whole body glucose levels
8
Q
How are the chains of glycogen arranged?
A
Like the branches of a tree
9
Q
Glycogen consist of chains of glucose originating from…
A
A dimer of the protein glycogenin
10
Q
Which bonds between glucose residues does glycogen contain?
A
a-1-4 glycosidic bonds
With a-1-6 glycosidic bonds forming branch points ever 8-10 residues
11
Q
How often are a-1-6 glycosidic bonds found between glucose residues in glycogen?
A
Every 8-10 residues
12
Q
Why can cellulose not be digested in humans?
A
There are no enzymes present to break down the B-1-4 glycosidic bonds
13
Q
Does synthesis of glycogen require energy? If so, in which form?
A
Yes
ATP, UTP
14
Q
Glucose has to be converted into which form to be added onto an existing glycogen chain?
A
UDP-glucose
15
Q
Which enzyme phosphorylates glucose to glucose-6-phosphate?
A
Hexokinase
In liver - glucokinase
16
Q
Which enzyme converts glucose-6-phosphate to glucose-1-phosphate?
A
Phosphoglucomutase
17
Q
Which enzyme forms UDP glucose from G1P?
A
G1P uridylyltransferase
18
Q
Which enzyme forms the a-1-4 glycosidic bonds seen in glycogen?
A
Glycogen synthase
19
Q
Which enzyme forms the a-1-6 glycosidic bonds seen in glycogen?
A
Branching enzyme
20
Q
What is glycogenolysis?
A
Glycogen degradation
21
Q
During glycogenolysis, glycogen is first broken down to which molecule?
A
Glucose-1-phosphate
22
Q
Which enzyme breaks the a-1-4 glycosidic bonds in glycogen?
A
Glycogen phosphorylase
23
Q
Which enzyme breaks the a-1-6 branches in glycogen?
A
De-branching enzyme
24
Q
Which enzyme converts glucose-1-phosphate into glucose-6-phosphate during glycogenolysis?
A
Phosphoglucomutase
25
Glucose-6-phosphate is produced as the end-product of glycogenolysis. What happens to this glucose-6-phosphate in the...
I) muscle
II) liver
I) glycolysis for energy production
II) converted to glucose released into the blood, travels to other tissues
26
What are the functions of glycogen in the liver?
Gluconeogenesis
G6P produced from glycogen degradation converted to glucose and released into the blood
27
Liver glycogen acts as a __________ of blood glucose levels
Buffer
28
Which enzyme converts glucose-6-phosphate to glucose in the liver? Why does this not take place in the muscle?
Glucose-6-phosphatase
Muscle does not have this enzyme
29
What is the function of glycogen in muscle?
To be broken down into glucose-6-phosphate which can enter glycolysis
30
Which enzyme regulates glycogen synthesis in liver? (Rate-limiting enzyme)
Glycogen synthase
31
Which enzyme regulate glycogen degradation in the liver?
| Rate-limiting enzyme
Glycogen phosphorylase
32
What effect does glucagon/adrenaline have on the activity of glycogen synthase and glycogen phosphorylase?
By which mechanism does it affect these enzymes?
Glycogen synthase - decreased
Glycogen phosphorylase - increased
Phosphorylation
33
What effect does insulin have on the activity of glycogen synthase and glycogen phosphorylase?
By which mechanism does it affect these enzymes?
Glycogen synthase - increased activity
Glycogen phosphorylase - decreased activity
De-phosphorylation
34
What effect does glucagon have on muscle glycogen stores?
No effect - no receptors for glucagon in muscle
35
What effect does AMP have on glycogen stores?
Only has an effect in the MUSCLE
Increases activity of glycogen phosphorylase
36
What type of disease are glycogen storage diseases? What do they involve?
Inherited diseases?
Deficiency or dysfunction of enzymes of glycogen metabolism
37
Excess glycogen storage can lead to...
Tissue damage
38
Dimished glycogen stores can lead to...
Hypoglycaemia/poor exercise tolerance
39
Give an example of a glycogen storage disease and its cause?
Von Gierke's disease
Glucose-6-phosphatase deficiency
40
What is gluconeogenesis?
Production of new glucose
41
When does gluconeogenesis occur?
Beyond ~8 hours of fasting when liver glycogen stores begin to deplete
42
Where does gluconeogenesis take place? (2)
In the liver
And to a lesser extent in the kidney cortex
43
What are three major precursors for gluconeogenesis?
Lactate
Glycerol
Amino acids
44
Where does the lactate come from that can be used as a precursor for gluconeogenesis?
From anaerobic glycolysis in exercising muscle and red blood cells
45
Where does the glycerol that can be used as a precursor for gluconeogenesis come from?
From the breakdown of TAGs in adipose tissue
46
Which amino acid is typically used as a precursor for gluconeogenesis?
Alanine
47
Why can there be no net synthesis of glucose from acetyl-CoA?
It is too small
48
What are three key enzymes in gluconeogenesis?
How do they play an important role in gluconeogenesis?
Glucose-6-phosphatase
Fructose-1,6-bisphosphatase
PEPCK
Bypass the irreversible reactions of glycolysis so the precursors can be used to synthesise new glucose
49
Which two key enzymes are involved in the regulation of gluconeogenesis?
PEPCK
| Fructose-1,6-bisphosphatase
50
PEPCK and fructose-1,6-bisphosphatase are regulated by hormones which respond to... (3)
Starvation/fasting
Prolonged exercise
Stress
51
Which hormone has an overall effect of stimulating gluconeogenesis?
Glucagon
| Cortisol
52
Which hormone has the overall effect of inhibiting gluconeogenesis?
Insulin
53
What effect does glucagon (and cortisol) have on PEPCK and fructose-1,6-bisphosphatase?
Increased amount of PEPCK
| Increased amount AND activity of fructose-1,6-bisphosphatase
54
What effect does insulin have on PEPCK and fructose-1,6-bisphosphatase?
Decreased amount of PEPCK
| Decreased amount AND activity of fructose-1,6-bisphosphatase
55
Which type of receptors does glucagon act on?
GPCR type receptors
56
What type of receptors does insulin work on?
Tyrosine kinase type receptors
57
What type of receptors does cortisol work on?
Intracellular steroid receptors
58
In what form are lipids stored?
As TAGs
59
What is a TAG composed of?
Glycerol and 3 fatty acids
60
Are lipids stored in hydrous or anhydrous form? In which tissue?
Anhydrous form - lipids are hydrophobic
Adipose tissue
61
How many kg of TAG will be found in a typical 70kg man?
~15kg
62
How does the energy content of TAGs compare to carbohydrates/protein?
Energy content per gram twice that of carbohydrate/protein
63
In what circumstances are TAGs used for energy production?
Prolonged exercise
Stress
Starvation
Pregnancy
64
Storage/mobilisation of fatty acid stores is under _____________ control
Hormonal
65
What happens to adipocytes as a result of weight gain?
Can increase in size around fourfold
| Then divide and increase total number of fat cells
66
How does an adipocyte appear under the microscope?
With a large lipid droplet and the cytoplasm/organelles pushed to the edge of the cell
67
Which enzyme in the small intestine breaks down fat into fatty acids and glycerol?
Pancreatic lipase
68
What happens to the fatty acids and glycerol formed from the breakdown of TAGs in the small intestine?
Reformed into TAGs in intestinal epithelial cells
69
What happens to the TAG molecules that are reformed in intestinal epithelial cells?
They are transported as chylomicrons in the lymphatic system
70
Where doe TAGs in the lymphatic system enter the blood?
Drains at the thoracic duct and enters the bloodstream via the left subclavian vein
71
Once TAGs enter the bloodstream what two purposes can they be used for?
Mobilisation - fatty acid oxidation to produce energy
| Storage - adipose tissue
72
Fatty acids are transported in the blood bound to...
Albumin
73
Fatty acid oxidation doesn't take place in which cells?
Cells without a mitochondria (e.g. RBCs)
| Brain - can't pass blood-brain barrier
74
Which enzyme is involved in the mobilisation of TAG from adipose tissue?
Hormone sensitive lipase
75
What effect do glucagon, adrenaline and insulin have on hormone sensitive lipase?
Glucagon/Adrenaline - Increase activity
Insulin - Decrease activity
76
What is lipogenesis?
Fatty acid synthesis
77
Where does lipogenesis mainly take place? What acts as the major source of the carbons required for lipogenesis?
Liver
Excess dietary glucose
78
Lipogenesis requires _______ and _______
ATP
NADPH
79
Describe the process of lipogenesis
1) Glucose ---> Pyruvate (Glycolysis - Cytoplasm)
2) Pyruvate ---> Acetyl CoA + Oxaloacetate ---> Citrate (Mitochondria)
3) Citrate ----> Acetyl CoA + Oxaloacetate (Cytoplasm)
4) Acetyl CoA ---> Malonyl CoA (acetyl CoA carboxylase)
5) Building of fatty acids by the sequential addition of 2 carbons provided by malonyl CoA (Fatty acid synthase complex)
80
What reaction is catalysed by...
I) Acetyl CoA carboxylase
II) Fatty acid synthase complex
I) Acetyl CoA ----> Maonlyl CoA (requires NADPH)
II) Fatty acids from sequential addition of 2 carbon units from malonyl CoA (requires ATP)
81
What is a key regulatory enzyme for lipogenesis?
Acetyl-CoA Carboxylase
82
Name two substances that increase the activity of acetyl CoA carboxylase
Insulin
| Citrate
83
Name two substances that decrease the activity of acetyl CoA carboxylase
Glucagon/adrenaline
| AMP
84
Is lipogenesis a reductive or oxidative process?
Reductive - requires NADPH
85
By which mechanism does insulin lead to decreased activity of hormone sensitive lipase?
By which mechanism does glucagon/adrenaline lead to increased activity of hormone sensitive lipase?
De-phosphorylation
Phosphorylation
86
Hormone sensitive lipase breaks down TAGs in adipose tissue to glycerol and fatty acids that travel in the blood. What happens to the glycerol produced?
Travels to the liver and used as a source of carbon or gluconeogenesis
87
Name 5 different classes of lipids
```
TAGs
Fatty acids
Cholesterol
Phospholipids
Vitamins A, D, E & K
```
88
In what two ways are lipids transported in the blood? Why can't lipids travel freely in the blood?
Bound to albumin (usually fatty acids) - only ~2%
As lipoprotein particles - ~98%
They are hydrophobic and insoluble so transported bound to carriers
89
What is the typical plasma lipid concentration range for TAGs?
0-2.0 mmol/L
90
What is the typical plasma lipid concentration range for total lipids?
4000 - 8500 mg/L
91
What is the structure of a phospholipid?
Choline, phosphate and glycerol (hydrophilic polar head)
Fatty acid tail (hydrophobic non-polar tail)
92
What are three structures that phospholipids can form?
Liposome
Micelle
Bilayer sheet
93
What is the structure of liposomes and micelles?
Liposome - bilayer of phospholipids in a sphere, with a central cavity
Micelle - single layer of phospholipids arranged in a sphere, with a cavity able to transport hydrophobic cargo
94
Where do we get most of our cholesterol from?
Most is synthesised in the liver
Some cholesterol is obtained in the diet
95
Where is most of the cholesterol in the body synthesised?
Liver
96
What are three functions of cholesterol?
Essential component of membranes (regulates fluidity)
Precursor for bile acids
Precursor for steroid hormones
97
What is an example of a steroid hormone?
Testosterone
98
In which form is cholesterol transported?
As cholesterol esters
99
What is the structure of a cholesterol ester?
Which enzyme catalyses the esterification of cholesterol ---> cholesterol ester?
Cholesterol with an added fatty acid
LCAT
100
What is the function of lipoproteins?
Transport lipids around the body
101
What is the general structure of a lipoprotein?
Consists of a phospholipid monolayer with a small amount of cholesterol
Has peripheral and integral apolipoproteins in its monlayer and a cargo within
102
What are two examples of peripheral apolipoproteins?
What are two examples of integral apolipoproteins?
apoC
apoE
apoA
apoB
103
Give three examples of cargo that can be transported in lipoproteins
Fat soluble vitamins
TAGs
Cholesterol ester
104
What are the 5 different types of lipoproteins (ordered by density)
```
Chylomicrons
VLDL
IDL
LDL
HDL
```
105
Chylomicrons are the main carrier of...
Dietary TAG
106
VLDLs are the main carrier of...
Liver synthesised TAGs
107
IDLs mainly carry...
Cholesterol
108
LDLs mainly carry...
'Bad' cholesterol
109
HDLs mainly carry...
'Good' cholesterol
110
Each type of lipoprotein contains variable amounts of ___________________
Apolipoproteins
111
How is the density of lipoproteins obtained?
By flotation ultracentrifugation
112
How is the density of lipoproteins related to their diameter?
Diameter inversely proportional to density
113
Chylomicrons are only normally present in the blood...
4-6 hours after a meal
114
What sort of appearance will chylomicrons take in a fluid, e.g. The blood?
Creamy appearance
115
Apolipoproteins can be either...
Integral or peripheral
116
State a structural and functional function of apolipoproteins?
Structural - package hydrophobic lipids
Functional - acts as a cofactor for enzymes/ligands for cell surface receptors
117
Chylomicrons are loaded in the _________ _____________ and ____________ added before entering the ______________ __________
Small intestine
ApoB-48
Lymphatic system
118
Which apolipoprotein is added to chylomicrons in the small intestine before they enter the lymphatic system?
ApoB-48
119
Where do chylomicrons in the lymphatic system drain into the bloodstream?
At the thoracic duct which drains into the left subclavian vein
120
What happens to the chylomicrons once they enter the blood at the left subclavian vein?
They acquire 2 new apoproteins - apoC and apoE
121
What is the function of apoC on chylomicrons?
It binds lipoprotein lipase on adipocytes and muscle, releasing the fatty acids into the cells
122
When does apoC dissociate from the chylomicrons? What happens to the chylomicron at this point?
When TAG content reduces to ~20%
Becomes a chylomicron remnant - returns to the liver
123
What happens to the chylomicron remnant in the liver?
LDL receptor on the hepatocyte binds to apoE and the chylomicron is taken up by receptor mediated endocytosis
124
By which process is the chylomicron remnant taken up by the hepatocyte?
Receptor mediated endocytosis
125
What happens to the remaining contents of chylomicrons in the hepatocytes?
Released by lysosomes for use in metabolism
126
What is the function of lipoprotein lipase?
What does it require as a cofactor?
Where is it found in the body?
Hydrolyses TAG in lipoproteins
ApoC-II
Attached to the surface of endothelial cells in capillaries of muscle/adipose
127
Where are VLDLs made?
In the liver
128
What is added to VLDLs during their formation?
ApoB100
ApoE
ApoC
129
The apoC and apoE added to VLDLs during their formation comes from...
HDL particles in the blood
130
How do VLDLs transport TAG to other tissues from the liver?
Bind to LPL on endothelial cells in muscles/adipose
| Becomes depleted of TAG
131
What are the fatty acids released from VLDLs used for in...
I) muscle
II) adipose
I) energy
II) storage
132
What happens to the VLDL as the TAG content drops?
VLDL dissociates from LPL and returns to the liver
133
When does a VLDL become an IDL?
When VLDL content drops to ~30%
134
What happens to the IDL once it is produced?
Either taken up by liver or rebinds to LPL
135
When does an IDL become an LDL? What changes does the lipoprotein undergo from IDL ---> LDL?
When depletion reaches ~10%
Loses apoC and apoE
136
What is the primary function of LDLs?
Provide cholesterol from the liver to peripheral tissues, peripheral cells express LDL receptor and take up LDL through receptor mediate endocytosis
137
Why are LDLs not efficiently cleared by the liver?
They do not have apoC or apoE
138
Why are LDLs associated with 'bad' cholesterol?
They have a long half life so are more susceptible to oxidative damage, oxidised LDLs are taken up by macrophages, forming foam cells which contribute to the formation of atherosclerotic plaques
139
What happens to oxidised LDLs?
Taken up by macrophages
| Macrophages ---> Foam cells
140
Foam cells contribute to the formation of...
Atherosclerotic plaques
141
Cells requiring cholesterol express which receptors?
What acts as a ligand for these receptors?
LDL receptors
ApoB-100
142
LDLs taken up by reactor mediated endocytosis fuse with...
Lysosomes to release cholesterol/fatty acids
143
What controls LDL receptor expression on the surface of cells?
Intracellular cholesterol concentration
144
Name three ways in which HDLs can be produced
Synthesised by the liver/intestine
Bud off from chylomicrons/VLDLs as they are digested
Free apoA-1 can acquire cholesterol and phospholipid to form HDLs
145
What happens to the initially 'empty' HDLs that are produced?
They accumulate phospholipid and cholesterol from cells lining blood vessels
146
Does the filling of HDLs with phospholipids/cholesterol from cells lining blood vessels require the activity of enzymes?
No
147
What is the function of HDLs?
Transport excess cholesterol from cells to the liver for disposal and bile salts or to other cells requiring cholesterol
148
Which protein within the cell allows the transfer of cholesterol to the HDL?
The cholesterol is converted into which form for transport in the HDL? Which enzyme catalyses this conversion?
ABCA1 protein
Cholesterol ester
LCAT
149
What two things can happen to a mature HDL?
Can be taken up by the liver ----> Bile salts
Can be taken up by other cells via scavenger receptors
150
How can HDLs interact with VLDLs?
They can exchange cholesterol ester for TAGs via cholesterol exchange transfer protein
151
Hyperlipoproteinaemias are either as a result of ___________________ or _________________
Over-production
| Under-removal
152
What is the cause of type I hyperlipoproteinaemia? What will be seen in type I hyperlipoproteinaemia?
Defective lipoprotein lipase
Chylomicrons in fasting plasma
153
What is the cause of type IIa hyperlipoproteinaemia?
Defective LDL receptor
154
What is the cause of type III hyperlipoproteinaemia? What will be seen?
Defective apoE
Raised IDL and chylomicron remnants
155
Hyperlipoproteinaemias (excluding type I) are associated with...
Coronary artery disease
156
What is Hypercholesterolaemia?
High level of cholesterol in the blood
157
Name 3 clinical signs of hypercholesterolaemia
Xanthelasma
Tendon Xanthoma
Corneal Arcus
All involve cholesterol deposition at different parts of the body
158
What is a xanthelasma?
Yellow patches on eyelids
159
What is tendon xanthoma?
Nodules on tendons
160
What is corneal arcus?
Obvious white circles around the eye
161
Raised serum LDL is associated with...
Formation of foam cells (lipid-laden macrophages)
Formation of fatty streaks
Formation of atherosclerotic plaques
162
What changes to the diet would be recommended in the treatment of hyperlipoproteinaemias?
Reduce cholesterol/saturated lipids in diet
| Increase fibre intake
163
What lifestyle changes would be recommended in the treatment of hyperlipoproteinaemias?
Increase exercise
| Stop smoking
164
Name two drugs that may be prescribed in the treatment of hyperlipoproteinaemias
Statins
Bile salt sequestrants
165
How do statins work in the treatment of hyperlipoproteinaemias?
Reduce cholesterol synthesis by inhibiting HMG-CoA reductase
166
How do bile salt sequestrants help in the treatment of hyperlipoproteinaemias?
Bind bile salts in the GI tract, forcing the liver to use more cholesterol to produce more bile salts
167
Total cholesterol:HDL ratio above __________ is considered high risk
6
168
What should TAG levels be in a fasted sample?
Less than 2 mmol/L
