32 - Integration and Regulation of Metabolism Flashcards
(68 cards)
1
Q
What are two ways in which metabolic pathways can be regulated by cellular energy?
A
- Direct regulation by ATP or AMP as allosteric regulator
- Regulation through AMP kinase (activated by high AMP)
This allows energy-costly processes to be inhibited when the cell cannot afford them
2
Q
What two enzymes are regulated in liver glycolysis? What regulates them?
A
- Pfk-1 (activated by AMP, inhibited by ATP)
- Pyruvate kinase (inhibited by ATP)
3
Q
What three enzymes are regulated in gluconeogenesis (in the liver)? What regulates them?
A
- Pyruvate carboxylase (inhibited by ADP)
- Phosphoenolpyruvate carboxykinase (PEPCK) (inhibited by ADP)
- Fructose-1,6-bisphosphatase (inhibited by AMP)
4
Q
What two proteins regulated fatty acid synthesis? What regulates them?
A
- acetyl-CoA carboxylase (inhibited by AMP kinase)
- Tricarboxylate transport (requires ATP to transport acetyl-CoA into cytosol)
5
Q
What enzyme regulates glycogenolysis in the liver? What regulates it?
A
- Non-phosphorylated phosphorylase (deactivated by ATP, activated by AMP)
6
Q
What enzyme regulates glycogen synthesis? What regulates it?
A
- Glycogen synthase (inhibited by AMP kinase)
7
Q
Long-term positive energy balance causes what in animals?
A
obesity
- Due to increasing energy storage with low energy expenditures
8
Q
What is the genetic component of obesity?
A
Susceptibility genes
- May impact food intake control and/or metbaolic efficiency
9
Q
What are the environmental components of obesity?
A
- Availability of food
- High calorie food
- Larger portion size
- Lack of physical activity
- Intestinal microflora
10
Q
What does leptin do? Where is it from?
A
Leptin from adipose tissue signals the presence of long term energy stores to decrease appetite and food intake
11
Q
What does insulin signal to the brain? Where is it from?
A
Signals acute availability of glucose/energy, decreases food intake and appetite. From the pancreas
12
Q
What does PYY and CKK from the small intestines do?
A
Signals from intestine when food is present, decreases appetite and food intake.
13
Q
What does ghrelin do? Where is it from?
A
Signals the absence of food from the stomach. It increases food intake
14
Q
Besides ghrelin, what other hormone increases food intake?
A
Cortisol, in response to stress increases food intake.
15
Q
What two types of neurons in the brain receive signals from appetite hormones? What inhibits and activates them? Which ones signal for more food intake? Less?
A
AgRP/NPY neurons and POMC neurons
- AgRP/NPY neurons send signals to increase food intake, they are inhibited by leptin and PYY, activated by ghrelin
- POMC neurons send signals to decrease food intake. They are activated by leptin
16
Q
What tissues have a lot of glucose/glycogen? (2)
A
Liver and muscle
17
Q
What tissue has a lot of triacylglycerols?
A
Adipose tissue
- The liver and muscle have a bit, but nowhere near as much as adipose tissue
18
Q
What tissue has the most mobilizable protein?
A
Muscle
19
Q
What two energy metabolites are secreted by adipose tissue?
A
Fatty acids + glycerol
20
Q
What two energy metabolites are secreted by muscle tissue?
A
Lactate + amino acids (alanine)
21
Q
What three energy metabolites are secreted by the liver?
A
Glucose + ketone bodies + lipoproteins
22
Q
What energy metabolites are secreted by the brain?
A
Trick question, none!
23
Q
What tissues/organs store energy for distribution? In what form?
A
- Liver (glucose/glycogen)
- Adipose tissue (triacylglycerols)
- Muscle (mobilizable protein)
24
Q
What is the metabolic goal during the ‘fed state (absorptive state)?’ Which hormone most active in this state
A
To remove glucose from blood and store energy for later. Insulin active
25
What are the metabolic goals in the post-absorptive state, what is the dominant hormone?
Povide glucose to the tissue that need glucose and provide energy to other tissues. Also maintain glucose levels in the blood.
Dominant hormone is glucagon
26
What are the metabolic goals during the fasting state? What is the dominant hormone?
The goals are the same as postabsorptive state, as well as to reduce glucose requirements as much as possible. Main hormone is glucagon.
27
What are the metabolic goals during exercise? What is the dominant hormone?
Provide energy to muscles and increase oxygen supply to muscle. Dominant hormone is epinephrine
28
What four things does insulin do to reduce blood glucose and build energy stores (anabolic)?
- Upregulation of GLUT4 transporter in muscle and adipose tissue
- Increased glycolysis
- Increased fatty acid uptake into adipose tissue
- Increased glycogen synthesis, fatty acid synthesis and protein synthesis
29
What five things does glucagon due to increase blood glucose and mobilize energy stores (catabolic)?
- Increased gluconeogenesis in liver
- Increased glycogenolysis (breakdown of glycogen),
- Increased lipolysis,
- Increased fatty acid oxidation
- Increased proteolysis
30
What happens to glucagon levels after a meal?
They decrease quickly.
31
Insulin inhibits glucagon secretion, does glucagon inhibit insulin secretion?
No, it promotes glycogenolysis, which increases blood glucose levels, which in turn activate insulin. So in a round about way, glucagon actually stimulate insulin release.
The key thing to remember though, is that insulin does directly inhibit the secretion of glucagon.
32
Total urinary nitrogen increases or decreases as a person fasts? Why?
Total urinary nitrogen decreases as a person fasts. This happens when growth hormone is suppressed by fasting, causing greater urea-nitrogen excretion, and therefore a drop in total urinary nitrogen. This is to strike a balance with free amino acids, which need nitrogen.
The accumulation of lipids in the liver is also involved with fasting, nitrogen and amino acids, but I'm not sure how...
33
When insulin stimulates adipocytes to take up glucose and store it as triacylglycerol, what happens?
- Insulin sensitive GLUT-4 glucose transporters on the adipocyte open
- Glucose enters the cell and is phosphorylated to glucose-6-phosphate
- It is then converted to pyruvate and glycerol by glycolysis
- Pyruvate is converted to acetyl-CoA, acetyl-CoA is then used to convert fatty acids (from gut chylomicrons and liver VLDLs) and the glycerol produced into triacylglycerol
34
How does the liver respond to high blood glucose levels?
Enters the absorptive phase
- Insulin insensitive GLUT2 transporters allow hepatocytes (liver cells) to intake glucose in a non-rate-limiting way.
1. Increaes phosphorylation of glucose by glucokinase
2. Converts G6P to glycogen
2. Converts G6P to pyruvate by glycolysis
2. Sends G6P into the pentose phosphate pathway
3. Fatty acid and TG synthesis with the acetyl-CoA produced from pyruvate and chylomicrons remnants uptake
4. Amino acid degradation also happens in the liver, able to become pyruvate, acetyl-CoA or enter TCA cycle, a side product of this is ammonia (NH3)
35
What does muscle do in the absorptive phase?
1. Intake glucose
2. Store glycogen
3. Uptake amino acids
4. Synthesize protein
Insulin sensitive GLUT4 transporters cause muscles to uptake glucose when insulin levels are high (like adipocytes)
36
What does the brain do in the absorptive phase (just after eating)?
Engages in glycolysis for energy production, resulting pyruvate is converted to acetyl-CoA for TCA cycle.
37
True or false? Muscles can use fatty acids for energy during the postabsorptive phase and fasting?
True
38
During the postabsorptive state and fasting, what three things can act as glucose precursors?
- Amino acids (from protein breakdown, as well as alanine from urea cycle)
- Lactate (from anaerobic respiration)
- Glycerol (from lipolysis in adipose tissue)
39
Lipolysis in adipose tissues provides two materials that act as precursors for energy giving molecules. What are these two precursors and what do they produce? And where?
- Glycerol (can be made into glucose in liver)
- Fatty acids (can be made into ketone bodies in the liver)
Fatty acids can also be used in muscles into amino acids in muscle, which can be converted to protein, which can be broken down into alanine, which can be made into glucose and urea in the urea cycle (in the liver)
40
Where is alanine (from muscle degradation) broken down into urea and glucose?
The liver
41
Why is aerobic exercise favoured over anaerobic exercise for burning fat?
Fatty acid metabolism is the principle energy production in cells during normal activity, producing acetyl-CoA with every two carbons taken off (this acetyl-CoA can then enter TCA cycle). To oxidize fatty acids however, oxygen is required. When cells are depleted of oxygen during anaerobic exercise, they are forced to use glucose in glycolysis to make energy (ATP)
42
How many ATPs are made in fatty acid oxidation?
For every two carbons cleaved
- 5 ATP made generating acetyl-CoA
- 12 more made oxidizing CoA
Total, 17 ATP and 1 CoA made per 2 carbons cleaved
43
What do adipocytes do during fasting phase?
Lipolysis, resulting in fatty acids bound to albumin being secreted in bloodstream.
- TG produce glycerol (which goes free into blood)
- TG also produce fatty acids, which can go into bloodstream with albumin or be converted to acetyl-CoA and enter TCA cycle in the cell.
44
What do muscles do during fasting phase (3 things)? What regulates this?
- Fatty acid breakdown for energy use
- Ketone body breakdown for energy use
- Proteolysis provides amino acids for liver gluconeogenesis
This isn't regulated by glucagon, but instead by nutrient availability, glucocorticoids, and other mechanisms.
45
What does the liver do during the fasting phase (4 things)?
- Glycogenolysis
- Gluconeogenesis
- Fatty acid oxidation
- Ketogenesis
46
What does the brain do during the fasting phase?
Uses ketone bodies for energy, by converting them to acetyl-CoA, which can be used in TCA cycle.
- However, even after very long starvation, ketone bodies cover only about 70% of energy, the brain always needs some glucose.
47
What is type 1 diabetes? (eg. what goes wrong
No insulin secretion from pancreas
48
What is type 2 diabetes?
Cells are resistant to insulin signal, even though insulin is present.
49
What type of state does diabetes cause in the presence of nutrients?
A catabolic state in the presence of nutrients.
- Glucose uptake is not stimulated (leading to increased blood glucose)
- Ongoing gluconeogenesis (increased blood glucose)
- Glycogen breakdown (increased blood glucose)
- Protein breakdown (abundant gluconeogenic precursors)
- Lipoprotein-TG uptake not stimulated (high lipids in blood)
- Lipolysis ongoing (higher free fatty acids in blood)
In sever type 1 diabetes, ketogenesis is stimulated by glucagon, this can lead to ketoacidosis.
50
What does insulin signal skeletal muscle to do? (5 things)
Upregulates:
- Glucose uptake
- Amino aid uptake
- Protein synthesis
- Glycogen synthesis
Downregulates
- Glycogenolysis
51
What four things does insulin signal adipose tissue to do?
Upregulates
- Glucose uptake
- Triacylglycerol synthesis
- Lipoprotein lipase
Downregulates
- Triglyceride hydrolysis
52
What 7 things does insulin trigger the liver to do?
Upregulates
- Glycogen synthesis
- Cholesterol synthesis
- Fatty acid synthesis
- Triacylglycerol synthesis
- Protein synthesis
Downregulates
- Glycogenolysis
- Ketogenesis
53
What enzymes of glycogen metabolism are activated by insulin (1) and inhibited by insulin (1)? What tissues does this take place in (2)?
Activated
- Glycogen synthase
Inhibited
- Glycogen phosphorylase
Liver and muscle tissue
54
What enzymes of glycolysis/gluconeogenesis are activated by insulin (2) and inhibited by insulin (2)? What tissues does this take place in (1)?
Activated
- Pfk2
- Pyruvate kinase
Inhibited
- FBPase-2 (F-2,6-BP)
- FBPase-1 (F-1,6-BP)
Liver
55
What enzymes (and coenzyme) of lipogenesis/lipolysis are activated by insulin (3) and inhibited by insulin (1)? What tissues does this take place in (2)?
Activated
- Acetyl-CoA
- Carboxylase
- Lipoprotein lipase
Inhibited
- Hormone sensitive lipase
Liver and adipose tissue
56
What enzymes of protein synthesis are activated by insulin (1) and inhibited by insulin (0)? What tissues does this take place in (1)?
Activated
- Various enzymes
Inhibited
- None
This happens in most tissues
57
What processes does glucagon upregulate and downregulate in adipose tissue? (1 each)
Upregulate
- Triacylglycerol hydrolysis
Downregulate
- Triglyceride synthesis
58
What processes does glucagon upregulate (3) and downregulate (3) in liver tissue?
Upregulate
- Glycogenolysis
- Ketogenesis
- Gluconeogenesis
Downregulate
- Glycogen synthesis
- Glycolysis
- Fatty acid synthesis
59
What type of tissue does glucagon not act upon? (that you might expect it to? What tissues does glucagon act on?
Doesn't act on
- Muscle
Acts on
- Liver and adipose tissue
60
What enzymes does glucagon activate (1) and inhibit (1) in glycogen metabolism in the liver?
Activates
- Glycogen phosphorylase
Inhibits
- Glycogen synthase
61
What enzymes does glucagon activate (2) and inhibit (2) in glycolysis/gluconeogenesis in the liver?
activates
- F2,6BPase
- Transcription of PEPCK
Inhibits
- Pfk-2
- Pyruvate kinase
62
What enzymes does glucagon activate (1) and inhibit (1) in lipogenesis and lipolysis in the liver and adipose tissue?
Activates
- Hormone-sensitive lipase
Inhibits
- Acetyl-CoA carboxylase
63
What process does glucagon inhibit in protein metabolism in liver cells?
Uptake of amino acids
64
What does epinephrine upregulate (3) and downregulate (1) in skeletal muscle?
Upregulate
- Glycogenolysis
- Glycolysis
- Lipoprotein lipase
Downregulates
- Glycogen synthesis
65
What does epinephrine do to the heart rate?
Increases it
66
What does epinephrine upregulate (1) and downregulate (1) in adipose tissue?
Same as glucagon
Upregulates
- Hormone sensitive lipase (triglyceride hydrolysis)
Downregulates
- Triacylglycerol synthesis
67
What does epinephrine upregulate (3) and downregulate (2) in the liver?
Same as glucagon
Upregulates
- Glycogenolysis
- Gluconeogenesis
- Ketogenesis
Downregulates
- Glycgeon synthesis
- Glycolysis
68
What four types of tissue does epinephrine affect?
- Skeletal muscle
- Cardiac muscle
- Adipose tissue
- Liver
