Valencik: Integration of Metabolism Flashcards
(87 cards)
1
Q
Each organ has a unique metabolic profile - how is it all coordinated?
A
nervous and hormonal signals
2
Q
Hormone of the well fed state: signal to stimulate storage of excess nutrients as glycogen and fat
A
insulin
3
Q
Three main targets of insulin
A
liver
adipose
muscle
4
Q
What stimulates insulin synthesis and release? What potentiates it?
A
glucose; amino acids
5
Q
What does insulin do to the following pathways in the liver, and what is the enzyme involved? glucose phosphorylation glycolysis gluconeogenesis glycogen synthesis glycogenolysis fatty acid synthesis pentose phosphate pathway
A
increase, glucokinase; increase, PFK1, pyruvate kinase; decrease, PEPCK, F16BPase, G6Pase; increase, glycogen synthase; decrease, glycogen phosphorylase; increase, acetyl-CoA carbox, ATP-citrate lyase, malic enzyme; increase, G6P DH
6
Q
What does insulin do to the following pathways in adipose tissue and what enzyme is involved? Glucose uptake Glycolysis Pentose phosphate pathway Pyruvate oxidation FFA uptake TAG synthesis Lipolysis
A
increases via Glut4 increases via PFK1 increases via G6P DH increases via pyruvate DH increases via LPL increases decreases via HSL
7
Q
This is the rate limiting step of glucose metabolism, increases glucose 10-20x in adipose and skeletal muscle in response to insulin
A
Glut4
8
Q
What does insulin do to the following pathways in skeletal muscle and what enzyme is involved? Glucose uptake Glycolysis Glycogen synthesis Glycogenolysis Protein synthesis
A
increases via Glut4 increases via PFK1 increases via glycogen synthase decreases via glycogen phosphorylase increases via translation
9
Q
Is glucose metabolism in the brain and RBCs insulin dependent?
A
No
10
Q
In summary, what does insulin do to the following and what enzyme is involved:
- glucose uptake (muscle, adipose)
- glucose uptake (liver)
- glycogen synthesis (liver, muscle)
- glycogen breakdown (liver, muscle)
- glycolysis, acetyl-CoA production (liver, muscle)
- fatty acid synthesis (liver)
- TAG synthesis (adipose tissue)
A
1.increase via increased GLUT4 transporter2.
2. increase via glucokinase
3. increase via glycogen synthase
4. decrease via glycogen phosphorylase
5. increase via PFK-1
increase via pyruvate DH
6. increase via acetyl-CoA carboxylase
7. increase via LPL
11
Q
Stimulates the liver to maintain blood glucose
Secreted by pancreatic alpha cells
Increases 2-3 fold by hypoglycemia
Reduced to 50% of basal levels during hyperglycemia
Acts through second messenger cAMP
A
glucagon
12
Q
What is the effect of glucagon in the liver on the following pathways? glycolysis gluconeogenesis glycogen synthesis glycogenolysis FA synthesis FA oxidation
A
decrease increase decrease increase decrease increase
13
Q
Fight-or-flight response, Acute, (response time is within seconds) and Chronic stress
A
catecolamines
14
Q
What is the pathway for formation of the catecholamines?
A
tyrosine –> L-DOPA –> Dopamine –> norepi –> epi
15
Q
What is the most important response of the catecholamines?
A
the mobilization of glycogen and fat for muscle use
16
Q
What potently stimulates catecholamine release?
What else stimulates release of catecholamines?
A
hypoglycemia; pain, hypoxia, and hemorrhage
17
Q
What does epinephrine do the following pathways in the liver? glycolysis gluconeogenesis glycogen synthesis glycogenolysis FA synthesis
A
decreases it increases it really decreases it really increases it decreases it
18
Q
How does epinephrine act on the liver?
A
Raises the Ca2+ level through a1 adrenergic receptors
19
Q
What does epinephrine do to the following in adipose tissue?
lipolysis
TAG uptake from lipoproteins
A
increases way
decreases
20
Q
How does epinephrine act on adipose tissue?
A
raises cAMP through beta-adrenergic receptors
21
Q
Direct effects of epinephrine on the pancreas?
glucagon secretion
insulin secretion
A
increases glucagon secretion (need more blood glucose!!!)
decreases insulin secretion
22
Q
What does epinephrine do to the following pathways in skeletal muscle? glycolysis glycogen synthesis glycogenolysis TAG uptake from lipoproteins
A
increases way
decreases way
increases way
increases
23
Q
What is the difference in effect on glycolysis by epinephrine in the liver vs the skeletal muscle?
A
In the liver, epinephrine reduces glycolysis, but in the skeletal muscle, it increases glycolysis and TAG uptake (counter-intuitive)
24
Q
Catecholamines through beta-adrenergic receptors and cAMP (blank) rather than inhibit glycolysis in skeletal muscle
A
stimulate
25
Cortisol is in large synergistic to epinephrine, but works through (blank) and accumulates over many hours to days
gene regulation
26
```
Cortisol stimulates:
(blank) degradation in adipose tissue
Breakdown of muscle (blank)
Gluconeogenesis to the liver
Glycogenesis
```
TAG; protein
27
Net effect of glucocorticoids
blood glucose restored
| glycogen stores increase
28
Effects of glucocorticoids on fuel metabolism: GCs stimulate (blank) in adipose tissue and the release of (blank) from muscle protein. In liver, GCs stimulate (blank) and the synthesis of (blank). The breakdown of liver glycogen is stimulated by (blank)
lipolysis; amino acids; gluconeogenesis; glycogen; epinephrine
29
What do glucocorticoids do to protein degradation in muscle? Protein synthesis in muscle? Glucose utilization?
Lipolysis in adipose tissue?
increase protein degradation; decrease protein synthesis; decrease glucose utilization; increase lipolysis
30
(blank) effects uptake and oxidation of fuels in adipose tissue, muscle and liver
growth hormone
31
Overall effect of growth hormone:
increases (blank) availability for energy generation
What is the benefit of this?
FFA; indirectly spares the oxidation of glucose and amino acids
32
```
Direct effects of growth hormone on adipose tissue:
Epi sensitivity
Insulin sensitivity
FA esterification
Insulin post receptor signaling
```
```
Indirect effects:
Lipogenesis
Plasma FFA + glycerol
TAG synthesis
Glucose uptake
```
increases
decreases
decreases
impaired
```
indirect:
increases
increases
decreases
decreases
```
33
```
Direct effects of growth hormone in the liver:
Protein synthesis
FFA oxidation
Gluconeogenesis
Glycolysis
```
Indirect:
IGF1
Ketogenesis
Glycogenesis
increases
increases
increases (increased glycerol)
decreases
Indirect:
increases
increases
increases
34
Effects of growth hormone on muscle:
FFA oxidation
AA transport
```
Indirect:
Glucose use
Glucose uptake
Glycolysis
Protein synthesis
```
increases
increases
```
Indirect:
decreases
decreases
decreases
increases
```
35
In the muscle, growth hormone spares these two things
glucose and protein
36
In the muscle, growth hormone causes positive (blank) balance
nitrogen
37
What does thyroid hormone do to fuel consumption? What does it do to sensitivity of receptors that have insulin counter-regulatory effects?
increases; increases
38
Effect of thyroid hormone on pancreatic beta-cells
increases sensitivity - leading to insulin release
39
Effects of thyroid hormone on adipose tissue:
Epinephrine sensitivity
Lypolysis
Insulin-->Glucose uptake-->TAG synthesis
This shows that effects of TH in adipose tissue can be bipolar!! What determines if TAG synthesis occurs?
increases; increases; increases
| the amount of glucose and insulin available
40
What determines if TAG synthesis occurs in adipose tissue?
the amount of glucose and insulin available
41
Effect of thyroid hormone in muscle:
Gene expression
Epi sensitivity
Indirect:
Glucose uptake
Protein synthesis
Glycogenolysis - Glycolysis
increases all
42
```
Effect of thyroid hormone on the liver:
Glycolysis
Cholesterol synthesis
Bile salts
Sensitivity to epinephrine --> gluconeogenesis --> glycogenolysis --> glucose
```
Indirect:
FFA --> TAGs
increases all
43
The liver is analogous to a (blank), while adipose tissue is analogous to a (blank). The liver processes fats, carbs, proteins from diet, synthesizes and distributes lipids, ketone bodies, and glucose for other tissues, and converts excess nitrogen to urea. Adipose tissue has 100x more energy than glycogen
checking account; savings account
44
Fasting increases FFAs (blank) times in plasma
4-8 times
45
What percent of dietary glucose is metabolized in the liver? The majority of glucose is made into (blank).
20-30%; glycogen;
46
What four pathways can Glucose-6-phosphate take?
1. can form glycogen in liver
2. can become blood glucose
3. can go through glycolysis to pyruvate
4. can go through PPP
47
What are three fates of acetyl-CoA?
1. TCA cycle (combined with OAA to form citrate)
2. cholesterol (through HMG coa)
3. Fatty acids (acetyl-CoA carboxylase)
48
In the liver, what is the first step in conversion of carbs (glucose) to fat?
glycolysis!
| glucose-6-P --> pyruvate --> acetyl-CoA --> fatty acids
49
The liver makes (blank) at all times
VLDL
50
What is the only major fate of FAs in the mitochondria?
B-oxidation
51
Acetyl-CoA is portioned between what two fates?
TCA cycle and ketogenesis (incomplete oxidation of FAs)
52
Carnitine palmitoyl transferase-1 is inhibited by (blank)
malonly-CoA
53
Acetyl-CoA carboxylase is stimulated by what two things?
insulin (indirectly)
| citrate
54
After a 12 hour fast, carnitine palmitoyl transferase-1 is induced by (blank) and there is no malonyl-CoA to inhibit it. Acetyl-CoA carboxylase is inhibited by by what three things?
glucagon; increased acyl-CoA, decreased citrate, and phosphorylation via glucagon/epi signaling
55
Liver after a 4 day fast:
What are the main sources of blood glucose?
What supplies ATP and NADH?
The (blank) is inhibited and (blank) enzymes are induced.
amino acids and lactate; a high rate of beta-oxidation; TCA cycle; ketogenic
56
The liver converts dietary carbohydrates to what?
| The liver supplies what two things during fasting?
glycogen and fat; glucose and ketone bodies
57
In adipocytes after a mixed meal, what does increased insulin do to HSL? Glucose uptake? LPL?
Therefore, what happens to FA synthesis because glucose --> DHAP --> glycerol phosphate?
inhibits HSL (HSL takes TAGs to glycerol + FFAs)
stimulates glucose uptake
stimulates LPL (LPL takes up components of chylomicrons)
increases FA synthesis
58
During fasting, what happens to fatty acids from LPL cleavage in adipocytes? What happens to HSL activity? What about transport of glucose to adipocytes?
fatty acids are taken to muscle and other tissues for oxidation and to the liver for ketogenesis; HSL is stimulated by epinephrine and takes TAGs to glycerol and FFAs; no more transport of glucose to adipocytes because no GLUT4
59
Muscle when well fed is strong and well supplied. When fasting, muscle is (blank) sparing and (blank) degrading.
glucose; protein
60
Does insulin stimulate LPL in muscle?
No
61
During starvation, what provides energy to the brain? During a normal diet, what supplies energy to the brain?
ketone bodies; glucose
62
Immediately after a calorie-rich meal, glucose, fatty acids, and amino acids enter the liver. Insulin released in response to the high blood glucose concentration stimulates (blank) uptake 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 (blank), which is used to synthesize fatty acids for export as (blank) in VLDLs to adipose and muscle tissue
glucose; Acetyl-CoA; TAGs
63
...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 lymphatic system, as (blank), from the intestine to muscle and adipose tissues.
PPP; amino acids; chylomicrons
64
Early in fasting, (blank) becomes the principal source of glucose for the brain? Liver (blank) is broken down. The G1P produced is converted to (blank) then to free glucose which is released into blood. What does the muscle use to produce ATP rather than using blood glucose? The (blank) produced by RBCs/muscle is converted to glucose in the liver.
the liver; glycogen; G6P; glycogenolysis; lactate
65
Later in fasting/starving, amino acids from degradation of (blank) in liver and muscle, and glycerol from the breakdown of (blank) in adipose tissue are used for gluconeogenesis. The liver uses (blank) as its main fuel, and excess (blank) is converted to ketone bodies.
proteins; TAGs; fatty acids; Acetyl-CoA
66
Many tissues use ketone bodies more easily than (blank) as a source for energy. This contributes to glucose sparing.
FAs
67
During starving, what two things provide glucose to the blood?
80% liver
| 20% kidneys
68
T/F: Pathways that maintain adequate levels of fuels in the blood (glycogenolysis, gluconeogenesis, lipolysis, proteolysis, and ketogenesis) are active in the starved state.
True
69
Gluconeogensis makes 80-160g glucose/day. 1/2 of this is used by the brain. During starvation, the brain will use up to 70% (blank) for energy. How long could ya survive on water and vitamins?
ketones; 100 days
70
Type 1 diabetes - no (blank) so lipolysis in adipose tissue is constantly stimulated
insulin
71
```
Type 1 diabetes: what happens to the following?
Glycolysis
Gluconeogenesis
Glycogen synthesis
Glycogenolysis
FA synthesis
FA oxidation
```
```
decreased
increased
decreased glycogen synthesis
increased glycogenolysis
decreased FA synthesis
increased FA oxidation
```
72
Type 1 diabetes patients tend to be thin. Why?
lipolysis in adipose tissue is constantly stimulated - increased FA oxidation - decreased FA synthesis
73
Type 1 diabetes:
Liver makes (blank)
Liver can't make (blank)
Adipose and muscle do not take up (blank)
(blank) in adipose tissue lipolysis
(blank) levels of plasma FFA
Increased (blank) of FFAs in beta-oxidation
(blank) are produced and ketoacidosis can be fatal
```
glucose
glycogen
glucose
increase
increased
B-oxidation
ketones
```
74
In type 2 diabetes, adipose and muscle do not take up (blank). Liver still makes (blank). Adipose tissue (blank) is not substantially increased. What happens to LPL activity? What happens to plasma lipoproteins?
glucose; glycogen; lipolysis; decreases; increases
75
Useless foreign chemicals that have to be removed from the body
Xenobiotics
| ex: plant metabolites, synthetic products, lipid-soluble products
76
Lipophilic xenobiotics must be metabolized to (blank)
water-soluble products
77
Where are lipophilic xenobiotics taken to water-soluble products? How does it happen?
in the liver, intestines, lungs
Phase 1: reactions that usually oxidize a metabolite by the attachment of one or more OH groups
Phase 2: the metabolite is conjugated with a hydrophilic molecule and the inactive products are excreted
78
Phase 1: monooxygenase reactions with (blank) - this hydroxylates a substrate
cyto P-450s
79
Phase 2: Conjugation reactions of drugs and other xenobiotics - where do most of these reactions take place? What happens once the xenobiotics are converted to water-soluble products?
in the liver; they are excreted in bile or in the urine
80
In contrast to insulin, glucagon works almost entirely on the (blank)
liver (no glucagon receptors in muscle/adipose tissue)
81
Two MAIN effects of glucocorticoids
1. RESTORE BLOOD GLUCOSE (GLUCONEOGENESIS)
| 2. RESTORE GLYCOGEN STORES
82
While glucocorticoids (cortisol) causes (blank) nitrogen balance and muscle wasting due to the degradation of protein, growth hormone causes (blank) nitrogen balance via the transport of AA
negative; positive
83
Overall, what seems to be the effect of thyroid hormone?
To increase GLUCOSE!
Increase gluconeogenesis
Increase glycogenolysis
84
After a fatty meal, what happens to LPL vs HSL activity?
You want LPL activity to be high so that chylomicrons are depositing FFAs to the adipose tissue for conversion into TAGs. You want HSL to be low, because it is what breaks down TAGs into glycerol and FFA
85
Differences between type 1 and type 2 diabetes
In type 1, no glycogen formation. In type 2, there will be glycogen formation because insulin is being produced. In type 1, there is lots of lipolysis. In type 2, not so much. In type 2, decreased LPL activity
86
What kind of receptor does epi bind to in the liver? in the muscle/adipose tissue?
alpha; beta adrenergic
87
How is cortisol different from epi?
| In terms of glycogen breakdown?
cortisol works thru gene regulation, epi works thru GPCRs
| cortisol is going to increase glycogenesis, while epi decreases glycogenesis
