Ch. 23 Metabolic Integration and Regulation Flashcards
(140 cards)
1
Q
What are hormones?
A
Small molecules or peptides that are secreted by one tissue and received by a receptor on another tissue.
2
Q
What does a cell require to receive a hormone?
A
It must have the proper receptor. Most cells have multiple types of hormone receptors.
3
Q
Why can cells have different responses to the same signal?
A
Two cells with the same hormone receptor can have wildly different responses due to intracellular signaling.
4
Q
What are hallmarks of hormone and receptor binding? (2)
A
Hormone receptors bind hormones with high specificity and high affinity so low [hormone] are needed.
5
Q
What are the types of instantaneous intracellular effects due to hormones? (4)
A
Second messengers (DAG, IP3, cAMP, Gɑ)
Receptor Tyrosine Kinases
Phosphotases
Receptors that trigger ion pores/ion channels
6
Q
What is the slower intracellular effect due to hormones?
A
Nuclear Receptors
7
Q
What are nuclear receptors and what does the ligand need to be?
A
Nuclear receptors always act on gene expression. The ligand must be partially hydrophobic because it has to go through the plasma membrane→cytosol→nuclear membrane.
8
Q
How is amplification present in hormone signaling?
A
One hormone binding to a receptor can lead to 100s or 1000s of second messengers being released.
9
Q
What are endocrine hormones?
A
Systemic hormones that are transported/secreted into the bloodstream.
10
Q
What are paracrine hormones?
A
Non-systemic hormones that are secreted by one cell and have an effect on a neighboring cell.
11
Q
What are autocrine hormones?
A
Hormones secreted from one cell with the receptor on the same cell. “Cell talking to itself.”
12
Q
What are peptide hormones made of?
A
Made up of amino acids, so a gene must code for them.
13
Q
How are peptide hormones usually expressed?
A
They are usually expressed as a larger, immature molecule that undergoes post-translational modification (usually proteolysis).
14
Q
Why are peptide hormones usually modified with proteolysis?
A
The pre/pro sequence of an immature peptide hormone molecule usually acts as an address label.
15
Q
What is preproinsulin and what does the prepro mean?
A
The immature form of insulin; the pre-sequence is an address label that tells the cell to send insulin to vesicles just inside the p.m.
16
Q
How does insulin get produced from preproinsulin?
A
Specific proteases cleave specific amino acid sequences on specific hormones. One protease cleaves the pre sequence and another cleaves the pro sequence.
17
Q
Where does preproinsulin end up in the cell?
A
It makes it to the secretory granules just inside the plasma membrane.
18
Q
Where do proteins that need to be transported get made?
A
ALL proteins that need to be transported are synthesized in the Golgi. ER→cis Golgi→trans Golgi.
19
Q
What are small molecule hormones?
A
Hormones that are made from metabolizing other molecules.
20
Q
How can tyrosine make a small molecule hormone? (2)
A
Tyrosine can be metabolized to dopamine and eventually get to epinephrine.
21
Q
Where does epinephrine production occur?
A
The metabolism of tyrosine to epinephrine occurs in the adrenal glands.
22
Q
Where is epinephrine stored?
A
Stored in secretory vesicles just inside the plasma membrane just like insulin.
23
Q
What do nuclear receptor hormones often start as?
A
They are small molecule hormones that usually start as cholesterol.
24
Q
What is the chemical nature of nuclear receptor hormones and how does this impact transport?
A
They are hydrophobic, so they are carried in the blood by transport proteins.
25
How do nuclear receptor hormones work?
They all work through gene expression.
26
What do cortisol, aldosterone, and testosterone each affect?
Cortisol (glucocorticoid from cholesterol): carbohydrate metabolism
Aldosterone (mineralocorticoid from cholesterol): uptake of Ca, K, and Na
Testosterone (sex hormone from cholesterol): reproduction
27
What is the systemic process of hormone signaling? (4)
1. Hypothalamus in the brain receives a signal starting the process of hormone release
2. Hypothalamus sends signal to pituitary gland
3. Pituitary glands send signal to the tissue that will synthesize and release hormone
4. Hormone is received by final target tissue
28
Why are there so many steps to hormone signaling? (3)
Multiple levels of regulation (positive and negative)
Amplification
Multiple stages of decision making (~modularity)
29
What are the consequences of the liver being well vasculated? (2)
Blood goes from the pancreas directly to the liver. Blood goes from the small intestine to the liver which means nutrients absorbed go to the liver first.
30
Why does the high amount of blood flow from the pancreas and small intestine mean for the liver?
The liver can handle constantly changing concentrations of metabolites.
31
Where does glucose mainly come from in the diet? (2)
Mainly starch and glycogen ingestion.
32
What happens immediately after ingesting glucose?
The liver immediately senses and increase in BGL.
33
What is glucokinase?
Glucokinase is a hexokinase isoform found in the liver. It phosphorylates any incoming glucose to G6P.
34
Why does BGL ≃ liver intracellular [glucose]?
The liver is insanely good at taking up glucose, and because of glucokinase the carbons stay trapped in the liver.
35
What is the fate of G6P? (5)
1. Dephosphorylated by G6Pase and released back into the blood when BGL is low
2. Used as a feedstock to make glycogen and maintain BGL in the future
3. Go to the citric acid cycle where carbons are oxidized to make energy or metabolites
4. Go through glycolysis and produce acetyl-CoA; acetyl-CoA will go through CA cycle, FA synthesis, and/or cholesterol production
5. Go through pentose phosphate pathway to produce NADPH and carbons for nucleotide production
36
Where do proteins come from in our diet?
We eat proteins.
37
What happens to proteins once eaten?
The stomach has proteases and a low pH that break down proteins→a.a. The a.a→small intestine→liver.
38
What is the fate of amino acids? (3)
1. Use amino acids to make liver proteins
2. Transport to the ER and secrete them so other cells can use them
3. Catabolize them and convert them to nucleotides with ammonia sent to the urea cycle
39
What happens to ketogenic amino acids?
Ketogenic amino acids are converted to nucleotides with ammonia to the urea cycle.
40
What happens to glycogenic amino acids?
Glycogenic amino acids are converted to pyruvate.
41
What happens to lipids in our diet?
Lipids are eaten and enter the small intestine→liver.
42
What is the fate of lipids? (4)
1. Liver can make phospholipids
2. Liver can do β-oxidation if the liver has low needs. Acetyl-CoA can go to ketone bodies and/or CA cycle
3. Fatty acids can be reassembled as TAGs and packaged into VLDL
4. Fatty acids can be secreted into blood and carried by serum albumen
43
Why is the liver essential in metabolic integration and regulation?
The liver determines where glucose, proteins, and lipids are going based on the regulation of its metabolic pathways,
44
What else does the liver do beside metabolic integration?
It also detoxifies/metabolizes other molecules very well. (e.g alcohol, drugs, ingested small molecules)
45
What are the two types of adipose tissue?
White adipose tissue (more abundant)
Brown adipose tissue
46
What is white adipose tissue?
It is almost completely hydrophobic with 60% of its weight being a lipid droplet.
47
What is a lipid droplet?
A phospholipid monolayer that contains TAGs and cholesterol esters ONLY.
48
How is adipose tissue usually regulated?
They are highly regulated by hormones like insulin and glucagon.
49
What do adipose tissues have on their plasma membrane and why?
The p.m. is full of hormone receptors. The hormones tell cells whether to store or release TAGs and therefore, size and number of adipocytes is under hormonal control.
50
What can adipocytes secrete?
Adipocytes can secrete their own hormones too.
51
What is brown adipose tissue?
The cells are slightly smaller and more vasculated than white adipose cells, but are FULL of mitochondria.
52
Why are brown adipose cells brown?
Becuase of cytochromes in the ETC of mitochondria.
53
What is thermogenin/uncoupling protein I?
An enzyme that makes the inner mitochondrial membrane leaky to protons. Glycolysis, CA cycle, and ETC crank out protons without ATP production so heat is produced instead. (It is found in brown adipose cells!)
54
What happens to brown fat over a lifetime?
Human infants have brown fat that changes to white fat within the first year. (SIDS?)
55
What are the two types of muscle?
Red muscle (slow twitch)
White muscle (fast twitch)
56
What is red muscle?
AKA slow twitch: don't contract very strongly but are resistant to fatigue (OxPhos)
ENDURANCE!
57
What do red muscles have a lot of? (2)
They are well vasculated (lots of oxygen delivery)
They have lots of mitochondria (lots of CO₂ removal)
58
What is white muscle?
AKA fast twitch: much stronger contractions that are faster, but are anaerobic (power lifting, hockey, sprint)
59
What is a main structural difference of white muscle compared to red muscle? (2)
White muscle doesn't have as many mitochondria and isn't as well vasculated.
60
What do muscles prefer as a fuel source?
They prefer fats via β-oxidation and acetyl-CoA
61
What muscles burn fats only? (state)
Resting muscles burn fat only.
62
What will muscles burn when working moderately hard?
They will burn anything when working moderately hard... ketone bodies, fats, glucose
63
What do rapidly working muscles burn?
They must work anaerobically, so they can't oxidize NADH/FADH2. It can only happen for a short time!
64
What does rapidly working muscle produce?
It will produce a backup of OxPhos metabolites and produce lactate.
65
What does the buildup of lactate cause in rapidly working muscles? (4ish steps)
lactic acid will build up in muscles→pH drops in muscles→hydrolysis of ATP is less energetic→contraction is not as strong or fast
66
What is phosphocreatine?
A molecule that can donate a phosphate to ADP to make ATP via creatine kinase. It is bidirectional!
67
What does phosphocreatine do for muscles?
It is a short term energy source that buffers [ATP] during anaerobic conditions.
68
Which phosphocreatine reaction direction is favored during exercise? Rest?
During exercise, the forward reaction is favored (make ATP). During rest, the reverse reaction is favored (make ADP).
69
What is the Cori Cycle?
It removes lactic acid buildup and is what anaerobic athletes train to do.
70
How does the Cori Cycle work? (6)
Lactic acid goes to the liver→liver does gluconeogenesis to make glucose→liver sends glucose to tissues→tissues convert glucose to pyruvate→pyruvate is fermented to lactate→lactate goes back to the liver.
71
How does heart muscle work and what fuel source does it prefer?
Heart muscle ONLY operates aerobically. It prefers fatty acids and β-oxidation.
72
What does heart muscle contain? What is it lacking?
It is FULL of mitochondria (50% volume). It has almost no glycogen.
73
What is fatal for heart muscle?
Any lack of oxygen is quickly fatal because there is no other energy source other than aerobic respiration.
74
Do brain cells store glycogen?
No. There is no glycogen storage, so there needs to be a constant supply of glucose.
75
How do brain cells work?
They operate aerobically and need a constant supply of oxygen.
76
What can brain cells burn in the absence of glucose?
They can burn ketone bodies in place of glucose, but oxygen is still needed. (ketone body→acetyl-CoA→CA cycle)
77
What is the path of insulin from production to use? (3)
Insulin is secreted by pancreatic β-cells into the blood. Blood and insulin go directly to the liver. Liver determines where carbon flows based on signaling and regulation.
78
Where is insulin made and why?
Insulin is a peptide, so it is made via protein synthesis. Made in the ER→Golgi→vesicles just inside the p.m.
79
What do β-cells have on their surface and what does this mean?
They have GLUT2 transporters ALWAYS on the surface of their p.m. This means that if BGL rises, β-cell intracellular [glucose] also rises.
80
What is the energy status of β-cells?
They have high levels of ATP and low levels of AMP and ADP.
81
What kind of pumps do β-cells have?
They have K⁺ pumps that allow K⁺ to leave the cell.
82
What inhibits K⁺ pumps?
ATP inhibits the pumps.
83
What is the typical intracellular charge of a β-cell?
Cells usually have a negative intracellular charge because potassium is leaving.
84
What happens when K⁺ pumps are blocked on β-cells? (4)
1.When blocked, you get β-cell depolarization (lose gradient)
2. Calcium channels open (voltage-gated)
3. Calcium pours into the cell and cytosolic [Ca] increases
4. high [Ca] causes secretory granules to fuse to the p.m. and Ca-dependent protein kinases are activated in the cytosol
85
What happens to β-cells if BGL decreases? (6)
1. If BGL decreases, β-cell intracellular [glucose] decreases
2. glycolysis, CA cycle, and OxPhos slow down
3. [ATP] falls back to baseline
4. K⁺ channels open and depolarize
5. Ca channels open and repolarize
6. Ca channels close and pumps remove Ca to return to baseline
86
What is glucagon secreted by and when?
It is secreted by pancreatic β-cells when BGL is low.
87
What does glucagon cause?
It causes an increase in BGL.
88
How does glucagon increase BGL? (3)
Glycogen is broken down to glucose by glycogen phosphorylase.
Glycolysis rate is decreased.
Fatty acid secretion by adipose tissue is increased.
89
What are the potential paths of FAs and TAGs released by an adipocyte in response to glucagon? (3)
Adipocytes release FAs and TAGs which go to the liver. The liver can...
1. release them directly as FAs and TAGs
2. package in TAGs and store in VLDL
3. convert to acetyl-CoA to produce ketone bodies
90
What are the insulin and glucagon levels during long-term fasting?
Insulin levels are nearly zero. Glucagon levels are high.
91
What happens in adipose tissue during long-term fasting?
In adipose tissue, TAGs are broken down into FFAs and glycerol.
92
Where can FFAs go once released from adipose tissue? (3)
FFAs can go to the bloodstream, liver, and/or target cells.
93
What happens to proteins during long-term fasting?
Under fasting conditions, cells start to catabolize proteins to get a.a's and the a.a's will be catabolized.
94
Where can the carbons in glucogenic amino acids go?
They can enter glycolysis.
95
Where can the carbons in ketogenic amino acids go?
They CANNOT enter glycolysis.
96
What happens to oxaloacetate during long-term fasting?
Oxaloacetate is withdrawn rapidly to do gluconeogenesis because BGL is very low and all carbon needs to go to replenishing it.
97
What happens as a result of oxaloacetate being drawn off rapidly due to fasting conditions?
Oxaloacetate levels are nearly zero, so acetyl-CoA builds up.
98
How will TAGs enter glycolysis during long-term fasting?
TAGs come into glycolysis as triose phosphates (because of gluconeogenesis)
99
What does epinephrine cause? (3)
1. It will cause glycogen phosphorylase activity to increase and breakdown glycogen into glucose
2. It will activate cAMP-dependent protein kinases that phosphorylate glycogen synthase inactivating it
3. It will increase lipase activity in adipocytes producing FFAs
100
What is cortisol?
A glucocorticoid hormone that affects glucose concentration.
101
What tissues does cortisol work on? (3)
It works on muscle, liver, and adipose tissue.
102
What does cortisol do? (2)
It stimulates nuclear receptors leading to changes in gene expression, but it is slow to turn on and slow to turn off.
It stimulates FA release from adipose tissue to get energy.
103
When is cortisol secreted?
It is secreted in response to stress and damage (and inflammation).
104
What is type I diabetes?
Early onset diabetes or insulin dependent diabetes that usually presents in youth. This is an autoimmune disease that attacks β-cells.
105
How is type I diabetes usually treated?
Treatment is insulin injections or pumps.
106
What is type II diabetes?
Late onset or non-insulin dependent diabetes associated with chronic obesity. These patients have plenty of insulin, but the receptors are desensitized and not expressed so insulin signaling doesn't occur.
107
Is type II diabetes permanent?
If caught early, you may be able to reverse the effects, but not always.
108
What is the problem with diabetes... why is it a disease?
No glucose transporters are sent to the p.m. so not glucose uptake occurs. Cells must turn to alternate fuels like FAs (which go to acetyl-CoA and then to ketone bodies).
109
What are the three ketone bodies?
acetoacetate
β-hydroxybuterate
acetone
110
What is ketoacidosis?
From low blood glucose. Ketosis and acidosis.
111
What is leptin?
A 167 amino acid peptide hormone that is thought to somehow control the set-point of body weight.
112
What happens if you knock out the leptin gene and breed mice with it?
Some mice will have leptin and some will be without (leptin knock-outs).
113
What happens to the leptin knock-out mice and how can this be reversed?
They eat ALL THE TIME, but can be rescued by injecting them directly with leptin.
114
Where are the leptin receptors found and what do they do once stimulated?
Leptin receptors are only in the hypothalamus and immediately curb appetite upon stimulation.
115
What is the hypothalamus?
An area of the brain that starts the signal transduction process of leptin and other hormones.
116
What does leptin release indicate about adipose tissue?
Leptin is a signal that adipose tissues have plenty of TAGs available (don't need to eat).
117
What systemic effect can leptin have? (3)
It will increase blood pressure, heart rate, and thermogenesis in brown fat.
118
What does leptin prevent?
Leptin prevents the release of neuropeptide Y (NPY).
119
What is neuropeptide Y (NPY)?
A strong signal that says "eat now" and levels will be elevated during a starvation response.
120
What is leptin blood level correlated with?
Leptin blood levels are correlated with size and number of adipocytes because it is secreted by adipocytes.
121
What will the levels of leptin and NPY be in people who lose weight?
Weight loss will cause people to have low leptin levels and high NPY levels causing them to be hungry all the time.
122
What is the name of the pathway that leptin works through?
Jack-Stat Pathway
123
Why didn't leptin injections "cure" diabetes and what did it indicate about obesity?
Obese people already have high leptin levels because of the correlation with adipocyte size and number, so adding more leptin doesn't affect appetite. There must be a disruption somewhere in the leptin signaling pathway.
124
What is adiponectin?
It is secreted by adipocytes and sensitizes other organs to insulin.
125
What do adiponectin receptors work via?
Adiponectin receptors work via AMP-dependent protein kinases (block anabolism because cell is in a low energy state).
126
What do AMP-dependent protein kinases do? (2)
They stimulate energy production pathways and monitor the energy status of cells.
127
What is ghrelin?
A peptide hormone (has a gene) produced by stomach cells that signals "I'm hungry".
128
What and where are ghrelin receptors?
Ghrelin receptors are GPCRs found in the pituitary gland and hypothalamus.
129
What is the trend of ghrelin blood levels? High? Low?
Blood levels of ghrelin will rise until you eat and dorap as soon as you eat. This cycle continues.
130
What does injection of ghrelin do?
Injection will cause immediate hunger regardless of fed state.
131
What is PYY?
A peptide secreted by the small intestine when food enters it that inhibits NPY, reducing hunger.
132
When do PYY levels rise?
PYY blood levels rise right after eating?
133
Why is PYY an area of interest in obesity?
Injection (not a pill because its a peptide and the stomach would break it down) could potentially reduce hunger.
134
If PYY injections are unfavorable, what are some potential options for alternate delivery (1) or treatment (1)?
Maybe we can make a form that withstands protease cleavage.
Maybe we can silence NPY mRNA with a vaccine.
135
Why is obesity a complex problem? (4)
You have to consider blood levels, entry into cells, different signaling pathways, and different responses in cells.
136
What is THC?
Lipid-based messengers that increase hunger and make food taste better.
137
Where does THC come from?
It comes from arachadonic acid.
138
What are endocannabinoids?
A kind of THC that is released as you eat and lead to a pleasure feeling.
139
Where are symbiotic microbes mainly found in humans?
The digestive system is FULL of these and everyone has a unique microbiome.
140
Why are microbes present in our digestive system? (2-ish)
Microbes have different metabolic pathways than us and our digestive system can take up their metabolites. They can have profound impacts on things like adipocyte size.
