Integration of Metabolism Flashcards
1
Q
What do you get when you put storage fuels, O2, and ATP together?
A
you get CO2, H20, and urea
2
Q
To maintain homeostasis what do you need?
A
continuous input of energy
3
Q
What does the liver do?
A
process fats, carbs, proteins from diet, syntehsizes and distributes lipids, ketone bodies, and glucose for other tissues, converts nitrogen to urea
4
Q
WHen the brain is well fed, how much glucose does it consume?
When it is fasting?
A
90g/day
30g/day
5
Q
What is considered the checking account of the body?
What is considered the savings account of the body?
how is this coordinated?
A
liver
adipose tissue
nervous and hormonal signals
6
Q
When you fast what happens to your adipose tissue?
A
you increase your FFAs
adipose tissue has 100X more energy than glycogen
7
Q
When are insulin levels the highest and what does it do?
A
after a high carb meal
stores glucose via liver adipose and muscle
8
Q
Besides glucose what else can potentiate insulin?
A
amino acids
9
Q
What does the liver use to transport glucose and is this a high or low affinity glucose transporters?
A
GLUT 2 (Km=15 mM)
10
Q
What does glucokinase do?
A
increase glucose phosphorylation
11
Q
What does PFKI and pyruvate kinase stimulate?
A
glycolysis
12
Q
What does PEPCK, F1,6 BPtase, and G6Ptase do?
A
Increases gluconeogenesis
13
Q
What does glycogen synthase do?
A
increase glycogen synthesis
14
Q
What does glycogen phosphorylase do?
A
increases glycogenolysis
15
Q
What does acetyl CoA carboxylase do?
A
it increases fatty acid synthesis
16
Q
What does ATP-citrate lyase do?
A
Converts citrate to OAA and acetyl coa for fatty acid synthesis
17
Q
What does the malic enzyme do?
A
Produces NADPH which is necessary for fatty acid biosynthesis (coverts malate to pyruvate)
18
Q
What does G6P dehydrogenase do?
A
The regulated step of the pentose phosphate pathway and the step that provides NADPH to allow for proper RBC development
19
Q
What are insulins affects on the liver?
A
increases glucose phosphorylation increases glycolysis decreases gluconeogenesis increase glycogen synthesis decreases glycogenolysis increase FA synthesis increase pentose phosphate pathway (i.e gets rid of glucose through storage or through breakdown and puts the breakdown products into other storage areas like FAs)
20
Q
What are insulin’s affects on adipose tissue?
A
increase glucose uptake increased glycolysis Increase PPP increase pyruvate oxidation(to become acetyl CoA) increase TAG (FFA) uptake Increase TAG synthesis decreased lipolysis
21
Q
What is the main idea of insulins affects on adipose tissue?
A
to decrease the amount of glucose via glycolysis and place the breakdown products (pyruvate) into storage (fat)
22
Q
How does insulin decrease lipolysis?
A
by inhibited HSL (the rate limiting step of lipolysis)
23
Q
How does insulin increase TAG (FFA) uptake?
A
Increases LPL which will turn release TAGS into capillaries
24
Q
How will insulin increase pyruvate oxidation?
A
by increasing pyruvate dehydogenase
25
How will insulin increase activity of PPP?
via increase in G6PD
26
How will insulin increase glucose uptake?
via Glut4 receptors (low affinity receptors)
27
How does insulin affect the skeletal muscle and how?
increases glucose uptake via GLUT4
Increase glucose breakdown via PFK1
increases protein synthesis by nonselective translation
increase glycogen synthesis via glycogen synthase
28
What breaks down glycogen?
Glycogen phosphorylase
29
What 2 things are insulin INDEPENDENT?
brain and RBCs cuz they need glucose NO MATTER WHAT
30
what kind of transporter does the brain use?
| What kind of transport does the RBC use?
Glut 3 Km (high affinity)
| Glut 1
31
Where does fatty acid synthesis take place?
in the liver
32
Where do you get increase glucose uptake via inuslin?
muscle, adipose tissue, liver
33
Where do you get increase glycogen synthesis via insulin?
liver and muscle
34
Where do you get increased glycolysis via insulin?
liver and muscle
35
Where do you get TAG synthesis via insulin?
adipose tissue
36
What does glucagon do?
makes glucose via cAMP second messengers
37
What is reduced to 50% of basal levels during hyperglycemia?
glucagon
38
How does glucagon effect the liver?
```
forms glucose (build up glucose and breaks down glycogen)
Breaks down fatty acids
```
39
So why does glucagon break down FA's and insulin build FAs?
because when you have glucagon you dont have enough glucose so you dont want to use glucose for energy so you want to build your glucose levels and break down your FAs for energy instead
40
How does glucagon decrease glycolysis?
by making down regulating PFK2 so that it cannot allosterically activate PFK1 and thus pyruvate kinase. Instead it will result in high levels of F6P and promote gluconeogenesis
41
How does glucagon increase gluconeogenesis?
Increases the activity of PEPCK, F1,6BPtase, G6Ptase
42
How does glucagon decrease glycogen synthase?
downregulates glycogen synthase
43
How does glucagon increase glycogenolysis?
increases glycogen phosphorylase :)
44
How does glucagon decrease FA synthesis?
It inhibits acetyl- Coa carboxylase
| remember acetyl Coa Carboxylase turns acetyla coa into malonyl coa into palmitic acid (FA)
45
How does glucagon increase FA oxidation?
it up regulates CPT1 (carnitine palmitoyl transferase 1) which will allow for acyl carnitine to cross the the mito membrane for beta oxidation
46
Where does glucagon exclusively act on?
the liver
47
What is the most important response of catecholamines?
mobilization of glycogen and fat for muscle use
48
Catecholamine release is potently stimulated by (blank). It is also stimulated by what 2 things?
hypoglycemia
| pain, hypoxia, and hemorrhage
49
Explain how you get epinephrine?
Tyrosine-> L-DOPA-> Dopamine-> Norepinephrine-> Epinephrine
50
How does epinephrine effect the liver?
Increases levels of glucose (by decreasing glycolysis and increasing gluconeogenesis, decreasing glycogenesis and increasing glycogenolysis)
Decrease levels of FA synthesis
51
How does epinephrine decrease glycolysis in the liver?
inhibits PFK2 so you end up with a lot of PFK1 and thus gluconeogenesis
52
How does epinephrine increase gluconeogenesis?
decreases pyruvate kinase levels and increase F26BPtase which will result in decreased levels of PFK1 and thus increased gluconeogenesis
53
How does epinephrine decrease glycogen synthesis in the liver and increase glycogenolysis?
It phosphorylates glycogen synthase (which takes away its activity) and phosphorylates glycogen phosphorylase thus increasing its activity
(remember glycogen phosphorylase is the first step in glycogen breakdown)
54
How does epinephrine decrease FA synthesis in the liver?
It decreases Acetyl-CoA Carboxylase activity (step that converts acetyl coa into malonyl coa to make fatty acids) by phosphorylating acetyl coa carboxylase which will deactivate it
55
What does epinephrine do to calcium levels?
raises calcium levels through alpha 1 adrenergic receptors via ca2+/calmodulin sensitive phosphorylase kinase which will make all the effects of epinephrine in the liver possible
56
(Blank) is activated via vasopressin, oxytocin, and angiotensin II via Ca2+ or phophpatidylinositol bisphosphatase.
Glycogenolysis
57
What are the effects of epinephrine on adipose tissue?
increased lipolysis and decreased TAG uptake from lipoproteins
58
How does epinephrine increase lipolysis in the adipose tissue?
By increasing HSL (hormone sensitive lipase) which will convert DAGs to MAGs :) and increase breakdown of fats
59
How does epinephrine decrease TAG uptake from lipoproteins in the adipose tissue?
by decreasing LPL levels
60
What is the mechanism that epinephrine affects adipose tissue?
Raise cAMP through B-adrenergic receptors
61
What are the effects of epinephrine on the pancreas?
increased glucagon secretion and decreased insulin secretion
62
What are the effects of epinephrine on the skeletal muscle?
increased glycolysis
decreased glycogen synthesis
increase glycogenolysis
increased TAG uptake from lipoproteins
63
How come in the skeletal muscle you get both increased glucose levels as well as increased breakdown of glucose via epinephrine?
Because F2,6 BP will stimulate PFK1 activity (i.e increase glycolysis) However the Kinase activity of PFK2-F2,6BPtase is sitmulated by cAMP induced phosphorylation SO what does this mean?
This means that epinephrine (which phosphorylates things) will phosphorylate PFK2 and it will act as a kinase !!! This kinase activity will stimulate glycolysis
64
So what will catecholamines do to glycolysis?
increases glycolysis via B-adrenergic receptors and cAMP (in muscle ONLY)
65
Explain the effects of epinephrine on the pancreas, liver, adipose, and muscle
glycogenolysis in muscle, liver
gluconeogenesis in liver
lipolysis in adipose tissue
glycolysis in liver
66
What hormone does epinephrine increase the secretion of?
glucagon (inhibits insulin)
67
How is cortisol regulated?
gene regulation
68
What is this:
| in large synergistic to epinephrine, but work through gene regulation and are cumulative over many hours and days
cortisol
69
What does cortisol stimulate in the liver, protein, and adipose tissue?
gluconeogenesis in the liver (increased PEPCK synthesis)
Breakdown of muscle protein
TAG degredation in adipose tissue (glucose sparing)
increased glycogenesis (excess G6P from gluconeogenesis)
70
What is the net effect of cortisol?
blood glucose restored, glycogen stores increase and you use fats (cuz glucose sparing)
71
What are the negative effects of long term cortisol secretion?
over time destroys muscle and bone and impairs endocrine and immune function
72
Explain the overall effects of glucocorticoids (i.e cortisol)
- stimulate fat breakdown in adipose tissue
- release of AAs from muscle protein
- in the liver stimulates gluconeogenesis and glycogen synthesis
73
The breakdown of liver glycogen is stimulated by what?
epinephrine
74
How do glucocorticoids increase lipolysis?
increased HSL activation
| Increased ATGL
75
How do you increase glucose levels in the liver with glucocorticoids?
via PEPCK synthesis and excess G6P
76
What is involved in nitrogen balance and muscle wasting?
glucocorticoids
77
What effects the uptake and oxidation of fuels in adipose tissue, muscle and liver?
Growth hormone
78
What is the overall action in growth hormones and what does this result in?
increases FFA availability for energy generation
| results: indirectly spares the oxidation of glucose and amino acids
79
What are the direct effects of growth hormone in the adipose tissue?
increases epinephrine sensitivity
decreased insulin sensitivity
decreased FA esterification (making TAGs)
impairs insulin post receptor signaling
(i.e increased sensitivity and esterification)
80
Since growth hormone in adipose tissue increases epinephrine sensitivity, what will be the indirect effect of this?
increased lipolysis (i.e. fatty acid degredation)
81
Since growth hormone in adipose tissue decreases insulin sensitivity, what will be the indirect effect of this?
increased plasma FFA and glycerol (i.e increased lipolysis)
82
Since growth hormone in adipose tissue decreases FA esterification what will be the indirect effect of this?
decreased TAG synthesis (remember FA esterification makes TAGS)
83
Since growth hormone in adipose tissue impairs insulin post receptor signaling what will the indirect effect be?
decreased glucose uptake
84
What are the direct effects of growth hormone on the liver?
increased protein synthesis
increase FFA oxidation
Increased gluconeogenesis (due to increased glycerol)
decreased glycolysis
85
Since GH hormone makes the liver increase protein synthesis, what will the indirect effect of this be?
increase IGF1 (insulin like GF effects on cell growth)
86
Since GH hormone makes the liver increase FFA oxidation, what will be the indirect effect of this?
increased ketogenesis
| remember fatty acids make ketone bodies
87
Since GH hormone makes the liver increase gluconeogenesis, what will be the indirect effect of this?
increased glycogenesis
88
What are the direct effects of growth hormone on the muscle?
increase FFA oxidation
increased AA transport (+ nitrogen balance)
impairs insulin post receptor signaling
89
Since GH hormone makes the muscle increase FFA oxidation, what will be the indirect effect of this?
decrease use of glucose (since you are using FFA you wont be needing to use glucose)
90
Since GH hormone makes the muscle have impaired insulin post receptor signaling, what will be the indirect effect of this?
decreased glucose uptake and decreased glycolysis
91
Since GH hormone makes the muscle increase AA transport, what will be the indirect effect of this?
increased protein synthesis
| allows for nitrogen balance and protein sparing
92
Does T4 or T3 have a longer half life?
T4 (remember less potent and lasts longer)
93
What are the main effects of thyroid hormones?
increased fuel consumption
| increased sensitivity of receptors that have insulin counter-regulatory effects (i.e. glucagon)
94
T or F, pathological effects of thryoid hormones are not simple extensions of physiological effects
T
95
How will Thyroid Hormone effect the pancreas?
it will increase the sensitivity of beta cells and thus increase insulin release
96
What are the effects of TH on adipose tissue?
increased epinephrine sensitivity and thus increased lypolysis
ABD
increased insulin secretion via the pancrea, thus increased glucose uptake and TAG synthesis
97
Isnt it weird that you have lipid breakdown and TAG synthesis in adipose tissue when TH is around?
yes it is therefore the amount of glucose and insulin available determines if TAG synthesis occurs
98
What are the direct effects of TH on the muscle?
increased Gene expression
| increased epi sensitivity
99
If TH causes increased Gene expression in the muscle, then what will be the indirect effect of this?
increased glucose uptake (via insulin)
| increased protein synthesis
100
If TH causes increase epi sensitivity, then what will be the indirect effect of this?
Increased glycogenolysis and increased glycolysis
101
What are the direct effects of TH on the liver?
increased glycolysis, cholesterol synthesis, increase cholesterole (and bile salts), increased sensitivity to epinephrine
102
If Th causes increased glycolysis in the liver, then what will be the indirect effect of this?
FFA being converted to TAGS in adipose tissue
103
If Th causes increased sensitivity to epinephrine in the liver, then what will be the indirect effect of this?
increased glucose (via gluconeogenesis, glycogenolysis)
104
What organ is central to metabolism?
liver
105
20-30% of dietary glucose is metabolized in the (blank). What happens to the majority of this glucose?
liver
| it is made into glycogen
106
Does the liver have LPL?
NO it doesnt, so it cant take in tags, can only take chylomicron remnants
107
In the liver, what is the first step in the conversion of carbs to fats
glycolysis
108
In the liver, what kind of lipoprotein will it make all the tiem?
VLDL
109
What is the only major fate of FAs in the mitochondria?
beta oxidation
110
In the liver, when fatty acids undergo breakdown/oxidation, what are the two places the breakdown products can go?
to make ketone bodies or go into TCA cycle
111
What is FA utilization controlled by?
substrate availability
112
After a meal in the liver, carnitine palmitoyl transferase-1 (for FA degredation) is inhibited by (blank) which will result in decreased FA degredation.
malonyl-CoA
113
After a meal in the liver, Acetyl-CoA carboxylase (FA synthesis) is stimulated by (blank) and (blank) which will result in increased FA synthesis
insulin (indirectly)
| citrate
114
3-4 hours after the meal the liver becomes a net producer of (blank)
glucose
115
After a 12 hour fast in the liver, carnitine palmitoyl transferase 1 is induced by (blank) and there is no malonyl CoA to inhibit it. What will this do?
glucagon
| increased FA degredation
116
After a 12 hour fast in the liver, acetyl- CoA carboxylase is inhibited by (blank), (blank) and (blank) via glucagon/epi signaling.
```
Increased acyl coA (intermediate in FA breakdown)
decreased citrate ( means your not having glycolysi)
phosphorylation
```
117
After a 4 day fast in the liver, what are the main sources of blood glucose?
amino acids and lactate
118
After a 4 day fast in the liver, what does a high rate of beta oxidation supply?
ATP and NADH
119
Since after a 4 day fast you have high rates of beta oxidation and thus high amounts of ATP and NADH, what will be inhibited and what will be induced?
TCA cycle is inhibited and ketogenic enzymes are induced
120
What does malonyl-Coa inhibit?
Fatty acid oxidation (degredation)
121
What does this do:
| 3-hydroxy-3-methyl-glutaryl-CoA lyase
conversation of HMGCoA to acetoacetate
122
50g of FA converted to acetoacetate supplies a lot of energy. It makes as much as (blank) grams of glucose from lactate.
190g
123
What happens to the liver after it is re-fed after a 4 day fast?
start using glucose primarily and start utilizing the TCA cycle and increasing FA synthesis and glycogen synthesis and TAG synthesis
124
How come in the 4 day fast stage (i.e. starvation) TCA cycle is inihibited?
because of high levels of ATP and NADH
125
The liver converts dietary carbohydrates to (blank) and (blank)
glycogen and fat
126
The liver supplies glucose and ketone bodies during (blank)
fasting
127
What do adipocytes do after a mixed meal?
```
inhibit HSL (so that you wont have FA degredation)
stimulates glucose uptake (Glut 4)
stimulates LPL (takes FA from blood and puts it into TAGS in adipocytes)
```
128
What are active in the starved state?
```
glycogenolysis
gluconeogenesis
lipolysis
proteolysis
ketogenesis
```
129
How come you can have increased FA synthesiss in the adipocyte after a mixed meal?
because glucose will be converted to DHAP which will be converted to glycerol phosphate
130
How do adipocytes respond during fasting?
TAGs are mobilized via increased HSL (i.e converted to FA and glycerol)
Increased Beta oxidation
131
How does HSL get stimulated in the adipocytes during fasting?
by epinephrine
132
Explain how the muscle maintains energy levels during the following stages:
Well Fed?
Fast?
strong and well supplies
| glucose sparing and protein degradation
133
Does muscle LPL get stimulated by insulin?
no
134
In the starved state how does the brain get energy?
uses ketones via beta hydroxybutyrate
135
Immediately after a calorie-rich meal, glucose, fatty acids, and amino acids enter the (blank). Insulin released in response to the high blood glucose concentration stimulates glucose (blank) by the tissues. Some glucose is exported to the brain for its energy needs, and some to adipose and muscle tissue. In the liver, excess glucose is oxidized to acetyl-CoA, which is used to synthesize (blank) for export as triacylglycerols in VLDLs to adipose and muscle tissue. The NADPH necessary for lipid synthesis is obtained by oxidation of glucose in the (blank). Excess (blank) are converted to pyruvate and acetyl-CoA, which are also used for lipid synthesis. Dietary fats move via the (blank) system, as chylomicrons, from the intestine to muscle and adipose tissues.
```
liver
uptake
fatty acids
pentose phosphate pathway
amino acids
lymphatic
```
136
Early in fasting, the muscle uses glycogenolysis to produce (blank) rather than using blood glucose (glucose sparing)
ATP
137
Early in fasting, the lactate produced by RBC's and muscle are converted to (blank) in the liver
glucose
138
Later during fasting what happens?
AAs from protein degredation in liver and muscle and glycerol from breakdown of TAGs in adipose tissue are used for gluconeogenesisq
139
Later during fasting, the (blank) uses fatty acids as its principal fuel, and excess acetyl-CoA is converted to ketone bodies for export to other tissues.
liver
140
During late fasting what 2 organs supply the bloodstream with glucose.
the liver (80%) and kidneys (20%)
141
During starvation, gluconeogenesis makes how much glucose/day?
80-160 g glucose/day (1/2 of this is made from AAs)
142
During starvation, the brain will use up to 70% (blank) for energy
ketones
143
Assuming you have 16kg Fat
and BMR 1500kcal/day,
you can survive ≈ (blank) days
on water and vitamins.
100
144
You lose 70-150g protein/day. When ≈1/3rd of the bodies nitrogen has been (blank) , it is too late to recover.
catabolized
145
What process are active in the starved state?
glycogenolysis, gluconeogenesis, lipolysis, proteolysis, and ketogenesis
146
Tell me about the metabolism of Type 1 diabetic patints
childhood autoimmune disease due to destruction of pancreatic beta cells which makes them insulin dependent.
Pnts tend to be thin
147
Why are type 1 diabetic patients typically thin?
lipolysis in adipose tissue is constantly stimulated cuz theres no insulin to shut it down.
148
```
Explain how all of these will be affected (i.e either increase or decrease) in type 1 diabetic patients:
glycolysis
gluconeogenesis
glycogen synthesis
glycogenolysis
FA synthesis
FA oxidation
```
```
decreased glycolysis
increased gluconeogenesis
decreased glycogen synthesis
increased glycogenolysis
decreased FA synthesis
Increased FA oxidation
(it will work as if they have a lot of glucagon)
```
149
Tell me about how the liver works in type 1 diabetics?
liver makes glucose (glucagon)
| liver cant make glycogen
150
What does this describe:
Adipose and muscle do not take up glucose (no Glut4 translocation.
↑Adipose tissue lipolysis (fasting response, epi and/or cortisol).
↑ plasma FFAs.
Liver →ß oxidation of FFAs
Ketones are produced and ketoacidosis can be fatal.
Liver makes glucose (glucagon).
****Liver CANT make glycogen (glucagon → GS-P and GP-P).
Type 1 diabetes
151
How do type 1 diabetics prevent ketoacidosis?
insulin injections
152
What is this:
Adipose and muscle do not take up glucose (Glut4).
*******Liver still makes glycogen (insulin).
Adipose tissue lipolysis is not substantially increased.
↓ LPL activity.
↑ Plasma lipoproteins.
Type 2 diabetes
| insulin resistance
153
What is an effective cure for type 2 diabetes?
diet and exercise
154
What is this:
Complex origins, ↓ insulin receptors and altered insulin signaling.
No Ketoacidosis, but hyper-osmolarity can dehydrate the brain leading to coma.
Type 2 diabetes
155
What is the worry with type 1 diabetes?
| what is the worry with type 2 diabetes?
ketoacidosis (can be fatal)
| hyperosmolarity resulting in dehydration in the brain and thus coma
156
Protein requirements are increased during what three things?
growth, trauma, and illness
157
(blank) can present in several forms depending on the age of the patient and the precipitating conditions, but the common feature is compromised immune function leading to decreased resistance to infection.
Protein/energy malnutrition
158
What are xenobiotics?
useless foreign chemicals that have to be removed from the body such as plant metabolites, synthetic products
159
Xenobiotics that are water soluble products are excreted in (blank) but lipid soluble ones are (blank)
urine or bile
| NOT
160
Lipophilic xenobiotics must be metabolized to (blank).
water soluble products
161
Where do lipophilic xenobiotics metabolize to water soluble products?
liver, intestines, lungs
162
What are the two phases that lipophlic xenobiotics are metabolized to water-soluble products?
phase 1: oxidization via addition of hydroxyl groups (this can increase or decrease toxicity)
phase 2: metabolite is conjugated with hydrophilic molecule (glucuronic acid, sulfate, glycine, glutamine, or glutathione) and inactive products are excreted
163
(blank) is a superfamily of heme-containing membrane bound proteins (14 families and at least 150 isoforms).
Generally found in the smooth ER of the liver and lungs.
Inducible enzyme (can effect metabolism of other drugs).
Broad substrate specificity.
Metabolizes xenobiotics :)
Cytochrome P-450
164
What is this:
Monooxygnease reactions with Cytochrome P-450 (electron carrier)
Substrate-H + O2 + NADPH + H+ → Substrate-OH + H2O + NADP +
Phase 1 of Lipophilic xenobiotic metabolism
165
The phase 2 of lipophilic xenobiotic metabolism typically takes place in the (Blank)
liver
