Lectures 11-15 Flashcards
(109 cards)
1
Q
What is Acetyl CoA derived from what? (For FA synthesis)
A
From beta-oxidation/the glycolysis reaction in the mitochondria
2
Q
How does glucagon work?
A
I’m works to raise the concentration of glucose and fatty acids in the bloodstream
3
Q
How does insulin work?
A
It acts to lower the concentration of glucose and fatty acids in the bloodstream
4
Q
How is lipogenesis regulated?
A
Acetyl CoA carboxylase
5
Q
Describe allosteric regulation during lipogenesis
A
Acetyl CoA carboxylase is activated by citrate
Tells the cell that Acetyl CoA and ATP are available for lipogenesis
6
Q
Describe hormone regulation during lipogenesis
A
Insulin promotes activation of Acetyl CoA carboxylase and therefore lipogenesis
7
Q
Slide 12
A
Lecture 11
Fatty acids synthesis simple
8
Q
What happens when there is an excess of glucose? (Fatty acid synthesis)
A
Fatty acids are synthesised in the cytosol of the cell from Acetyl CoA
9
Q
How do we get Acetyl CoA? (Fatty acid synthesis)
A
From the ‘link reaction’ which links glycolysis and the TCA cycle
10
Q
Acetyl CoA is synthesised to form what? (Fatty acid synthesis)
A
Malonyl CoA
11
Q
When is fatty acid synthesis inhibited? (Fatty acid synthesis)
A
When there are plenty of fatty acids in the cell
12
Q
When is fatty acid synthesis activated?
A
By excess glucose
And/Or
A decrease in fatty acid availability
13
Q
The Malonyl CoA is used for what? (Fatty acid synthesis)
A
To create a new fatty acid
14
Q
What is triglyceride synthesis?
A
Joining 3 fatty acids together with a glycerol
15
Q
When is triglyceride synthesis more likely to occur? And less likely to occur?
A
More - after each meal
After - during exercise
16
Q
How is a triglyceride formed?
A
Three fatty acids are attached to a glycerol backbone
17
Q
Triglyceride synthesis is promoted by what?
A
Insulin
18
Q
Triglyceride synthesis is inhibited by what?
A
Glucagon
19
Q
What are the 3 main ketone bodies we have to know?
A
Acetoacetic acid
3-hydroxybutyric acid
Acetone
20
Q
Are ketone bodies produced in large quantities?
A
No, they are produced in small quantities
21
Q
What can ketone bodies be a fuel source for? And when would they be used?
A
For brain - when glucose availability is low
22
Q
When do ketone bodies increase?
A
During hunger
Reduced carbohydrate availability
Starvation
Prolonged exercise
(Basically when there is a large amount of FA use)
23
Q
During circumstances when there is a large amount of FA use, why does ketone body production increase?
A
When large amounts of FA are used, the liver cannot oxidise then quick enough, so the increased Acetyl CoA available is converted to ketone bodies
These are then released in the blood for energy
24
Q
How are ketone bodies transported?
A
The blood
25
What organs use ketone bodies?
Brain
Heart
Kidney
Skeletal muscle
26
Why does the brain/heart/kidneys/skeletal muscle use ketone bodies?
To produce ATP via the TCA cycle in these cells
27
What has to happen to ketone bodies before they can be used to produce ATP via the TCA cycle in certain tissues?
Has to be re-concerted back to Acetyl CoA
28
What you really need to know slide
Lecture 11, slide 22
29
What are hormones?
Chemical messengers that regulate and co-ordinate metabolic activity within the body
30
What is an endocrine hormone?
A hormone produced in one tissue (gland) and travel through circulation to reach a target cell which has a receptor for that hormone
31
What is a paracrine hormone?
A hormone produced in one cell and only travels a short distance to reach a neighbouring target cell which has a receptor for that hormone
32
What is an autocrine hormone?
A hormone produced in a cell which is also the target cell for that hormone
33
What triggers insulin and glucagon?
Pancreas
34
What glands produce Adrenalin?
Adrenal glands
35
Are insulin and glucagon triggered by the hypothalamus?
No
36
What is the hormonal cascade?
Hormones released by one gland often stimulate the release of a hormone from another gland
37
How many different types of endocrine hormone are there?
Three
38
What are the different types of endocrine hormones?
Steroid
Peptide/protein
Amino acid derived (catecholamines)
39
What do the different types of endocrine hormones differ in?
Solubility characteristics
Mechanism of action
Speed of action
40
Describe the steroid type of endocrine hormone - are they lipid soluble?
Yes
41
Describe the steroid type of endocrine hormone - what is their structure?
A basic steroid structure
42
Describe the steroid type of endocrine hormone - how are they transported?
In the blood bound to specific transport proteins
43
Describe the steroid type of endocrine hormone - how do they enter the target cell?
The transport protein binds to a receptor on the cell surface, the hormone then enters the target cell
44
Describe the steroid type of endocrine hormone - how does the hormone act?
Binds to specific receptors (either in cytosol or nucleus)
If it binds to the cytosol the whole complex moves into nucleus
The hormone-receptor complex binds to specific regions of DNA
45
Describe the steroid type of endocrine hormone - what happens once the hormone-receptor complex is bound to a specific region of DNA?
Influences transcription (up or down)
Alters proportions of specific proteins in a cell
Slow response hormone
46
Describe the peptide/protein and amino acid derived (catecholamines) types of endocrine hormone - what size are they?
Small molecules - proteins/peptides/amino acid derivatives
47
Describe the peptide/protein and amino acid derived (catecholamines) types of endocrine hormone - how are they transported?
In free form in blood
48
Describe the peptide/protein and amino acid derived (catecholamines) types of endocrine hormone - how do they act?
They bind to specific cell surface receptors on the outside of the cell
They do not enter the cell
This binding initiated response in the target cell via second messenger
49
Describe the peptide/protein and amino acid derived (catecholamines) types of endocrine hormone - what is the main function?
To influence activity of proteins already present in cells
50
Describe the peptide/protein and amino acid derived (catecholamines) types of endocrine hormone - how long does the change in the cell take once hormone is bound etc?
There is a rapid response to the hormone
51
Describe the peptide/protein and amino acid derived (catecholamines) receptors - what are they?
Transmembrane proteins with distinct domains
A ligand binding domain to interact with the hormone of the cell surface
Transmembrane domains crossing the membrane
52
Describe the peptide/protein and amino acid derived (catecholamines) receptors - what happens after the binding of a hormone?
Induced a conformational change which results in either activation of intrinsic enzyme activity
Or
Interaction with other proteins in the membrane to affect enzyme activity
53
What type of peptide and catecholamine receptor activates intrinsic enzyme activity?
Receptor tyrosine kinase
54
What type of peptide and catecholamine receptor activates interaction with other proteins in the membrane to affect enzyme activity?
G Protein-linked receptor
55
Describe the peptide/protein and amino acid derived (catecholamines) receptors - what is the effect of enzyme activation?
Induces a second messenger to be formed within the cell
56
Describe the peptide/protein and amino acid derived (catecholamines) receptors - what do the second messengers activate?
A phosphorylation cascade initiated by protein kinases (PKs) which phosphorylate Ser or Thr residues on existing cell proteins
57
Describe the peptide/protein and amino acid derived (catecholamines) receptors - what does phosphorylation of specific proteins do?
Converts them from inactive to active or vica versa, depending on the protein
58
What is the process of signal transduction?
Signal -> Receptor -> Transduction -> Effect
59
Describe G-protein linked receptors - how many subunits are there?
Three
60
Describe G-protein linked receptors - what are the different subunits?
Alpha
Beta
Gamma
61
Describe G-protein linked receptors - when the hormone binds to its receptor what does induce?
A change in shape in the intracellular part of the receptor molecule
62
Describe G-protein linked receptors - what happens when the G protein interacts with the receptor?
It induces a change in the confirmation of the alpha subunit and replacement of GDP with GTP
63
Describe G-protein linked receptors - what happens after conformational change of the alpha subunit?
The alpha subunit also interacts with its target enzyme
64
Describe G-protein linked receptors - are G proteins stimulators or inhibitory?
Can be either stimulatory (Gs and Gq) or inhibitory (Gi) depending upon whether the alpha subunit is stimulatory or inhibitory
65
Lectures 13&14 in folder
With recap, go through process she drew up on the board
Slide 19 (lecture 13 pp)
66
G protein activation stuff
Slide 19, 22&23
| Lecture 13
67
What are tyrosine specific kinases?
Transmembrane receptor proteins (insulin receptor)
68
Describe tyrosine specific kinases - what happens when their “x” binds
Also what is “x”
“x” = ligand
It causes a conformational change
69
Describe G-protein linked receptors - what happens after the conformational change
It becomes a tyrosine kinase
70
What does tyrosine kinase initiate?
It initiates cascades
71
What cascades does tyrosine kinase initiate?
PIP3 and protein kinase B (PK(small B))
72
Insulin responsive substrate (IRS-1) has two functions in the PIP3 - PK(small B) cascade - what is the first function?
It binds to and activated the enzyme PI-3K which forms PIP3 from PIP2 in the membrane
73
Insulin responsive substrate (IRS-1) has two functions in the PIP3 - PK(small B) cascade - what happens as a result of the first function?
PIP3 attracts protein kinase B (PK(small B), Akt) which when bound to PIP3 is activated by phosphorylation by the enzyme PDK1
Active PK(small B) is then able to phosphorylate specific proteins modifying their activity
74
Insulin responsive substrate (IRS-1) has two functions in the PIP3 - PK(small B) cascade - what is the second function?
It phosphorylate other proteins which influence gene expression
75
The specificity of proteins for individual ligand gives proteins many of their functions such as:
Catalysis
Recognition
Transport
76
Describe the characteristics of proteins showing sigmoidal kinetics - how many subunits?
Two or more
77
Describe the characteristics of proteins showing sigmoidal kinetics - what shape are the subunits?
They can exist in two different shapes
78
Describe the characteristics of proteins showing sigmoidal kinetics - when a target ligand binds to the binding site on one of the sub-units what happens? What is this called?
It increases the affinity of the other sub-units for the ligand
Co-operative binding or cooperativity
79
Describe the characteristics of proteins showing sigmoidal kinetics - what does co-operative binding or co-operativity give rise too?
The sigmoidal curve
80
Describe the characteristics of proteins showing sigmoidal kinetics - what groups show sigmoidal kinetics?
Allosteric enzymes are only one of the groups of proteins that show sigmoidal kinetics
81
What is an allosteric protein?
A protein with multiple ligand-binding sites, such that ligand binding at one site affects ligand binding at another (known as cooperative binding)
82
Look at allosteric proteins
Slide 4, lecture 15
83
Look at effects of positive effectors on sigmoidal curve
Slide 8, lecture 15
84
Questions - Slide 9-15
Lecture 15
85
```
If a cell has high energy stores, it will have:
High/low - ATP
High/low - AMP/ADP
High/low - NAD+
High/low - NADH+H+
```
High ATP
Low ADP/AMP (because most has been converted to ATP)
Low NAD+ (because most is in the form of NADH+H+ waiting to be oxidised through mitochondrial electron transport chain)
High NADH+H+
86
How do positive effectors act on allosteric proteins?
They enhance the activity of the protein
87
How do negative effectors act on allosteric proteins?
They decrease the proteins activity
88
What is the allosteric enzyme in the glycogenolysis pathway?
What is this allosteric enzymes positive effector
What is this allosteric enzymes negative effector?
Allosteric enzyme = glycogen phosphorylase
Positive effector = AMP
Negative effector = ATP
89
What are the allosteric enzymes in glycolysis?
Hexokinase
PFK
Pyruvate kinase
90
What is the positive and negative effector of PFK? (One of the allosteric enzymes present in glycolysis)
Positive = AMP
Negative = ATP
91
What is the negative effector of pyruvate kinase? (One of the allosteric enzymes present in glycolysis)
ATP
92
What are the allosteric enzymes present in the TCA cycle?
Pyruvate deHase
Citrate synthase
Isocitrate deHase
93
What are the positive and negative effectors of Pyruvate deHase? (One of the allosteric enzymes present in the TCA cycle)
Positive = AMP, NAD+
Negative = NADH
94
What is the negative effector of Citrate Synthase? (One of the allosteric enzymes present in the TCA cycle)
Negative = ATP
95
What are the negative and positive effectors of Isocitrate deHase? (One of the allosteric enzymes present in the TCA cycle)
Positive = ADP
Negative = NADH
96
What may happen once control enzymes have been turned off/on?
There may be a build up in concentration of their substrates/products
These substrates/products may act as allosteric effectors of the other enzymes
97
What happens when the allosteric enzyme PFK is turned off? (Slide 17, lecture 15)
There is a build up of its substrate Glc-6-P
Glc-6-P acts as a -ve effector for glycogen phosphorylase and hexokinase
This reduces flow of glucose into glycolysis
98
What happens when the allosteric enzyme citrate synthase is turned off? (Slide 18, lecture 15)
When citrate synthase is turned off there is a build up of its substrates Acetyl CoA
Acetyl CoA acts as a -ve effector for pyruvate dehydrogenase (product inhibition)
This reduces flow of metabolites from glucose into TCA cycle
99
What happens if the flow of metabolites into the TCA cycle is not turned off quickly enough? What is the effect of this? (slide 18, lecture 15)
The concentration of citrate rises
Citrate acts as a -ve inhibitor of PFK
100
What happens when PFK is turned on? (Slide 18, lecture 15)
When PFK is turned on there is a build up of Fru-1,6-bP
| Fru-1,6-bP acts as a +ve effector for pyruvate kinase
101
Go over lecture 15
Dr Helen Mason one
102
Slides 20-22
Lecture 15
103
If a cell has high energy stores it will:
Need to convert excessive ATP into glycogen or lipids because you have too much
This acts as a store for periods of starvation
104
If a cell needs energy it will:
Release energy generating nutrients from stores
| These will go through the energy generating pathways to yield ATP
105
What is the negative effector of the allosteric enzyme glycogen synthetase? (Energy storage pathways) (which acts in what process)
ADP
Glycogen synthesis
106
What are the allosteric enzymes involved in gluconeogenesis? (Energy storage pathways)
Fru-1,6-bPase
Pyruvate carboxylase
PEPCK
107
Positive and negative effector of the allosteric enzyme involved in gluconeogenesis Fru-1,6-bPase? (Energy storage pathways)
Positive = ATP
Negative = AMP
108
Negative effector of the allosteric enzyme involved in gluconeogenesis pyruvate carboxylase? (Energy storage pathways)
ADP
109
Negative effector of the allosteric enzyme involved in gluconeogenesis PEPCK? (Energy storage pathways)
GDP
