Integration of Metabolism. Flashcards
1
Q
How much oxygen does the Brain use at rest?
A
20% of resting O2
2
Q
In the fed state, the brain relies primarily on ____ for energy?
A
Glucose
3
Q
How is glucose transported in the endothelial cells of capillary walls?
A
GLUT1
4
Q
How is glucose transported in neurons?
A
GLUT3
5
Q
What is the mechanism of GLUT1 and GLUT3?
A
Facilitated Diffusion
6
Q
During a fast what is the main alternative fuel for the brain?
A
Ketones
7
Q
How do ketones enter the brain?
A
Monocarboxylate transporters [MCT]
8
Q
During starvation what proportion of fuel does glucose make up for the brain?
A
1/3rd of the Brain’s fuel is glucose even in starvation.
9
Q
What is the route that all nutrients take to get to the liver following ingestion?
A
Portal Vein
10
Q
Why is the Liver in metabolism?
A
It plays a central role in glucose homeostasis.
11
Q
How does the liver control glucose homeostasis:
A
- Synthesizes glycogen from glucose
- Gluconeogenesis: Makes glucose from non-carb precursors.
- Releases glucose during the post-absorptive state.
- Responds to insulin and glucagon that regulate blood glucose levels.
12
Q
What is the energy utilization of Skeletal muscle at rest and during vigorous exercise.
A
- At Rest: 30% total oxygen
- Vigorous Exercise: 90% total oxygen
13
Q
What are the major characteristics of Brown Adipose Tissue (BAT)?
A
- Utilize uncoupling protein 1
- Plays an important role in thermogenesis.
14
Q
What are the major characteristics of White adipose Tissue (WAT)?
A
- Principle function: Storage of Triglycerides
-
Two forms:
- Subcutaneous (under skin)
- Visceral (Abdominal cavity and around organs): VERY BAD
-
Beige Adipocytes
- WAT cells that gain traits of BAT
- Secrete adipokines that have signal functions.
- Example: Leptin
15
Q
What are two major regulators of Fuel Homeostasis?
A
Insulin and Glucagon
16
Q
Role of insulin?
A
Promotes utilization and storage of nutrients following ingestion of a meal.
17
Q
Role of Glucagon?
A
Acts primarily on the liver to mobilize glucose when exogenous nutrients are unavailable.
18
Q
Insulin follows a daily pattern with _____ following a meal, and a sustained _______ that occurs in the abscence of stimuli.
A
Episodic Peaks
Low Basal Level
19
Q
What is the principle physiological stimulus for insulin release?
A
Glucose
20
Q
Insulin is released by what cells?
A
Pancreatic Beta-cells
21
Q
How does glucose enter into B-cells to induce insulin release?
A
GLUT2
22
Q
What happens to glucose once it enters into the B-cell and what is the mechanism for insulin release?
A
- Glucose is phosphorylated into glucose 6-phosphate
- G6P is then metabolized which results in an increase in intracellular concentration of ATP
- Increasing ATP levels inhibit K+ efflux through ATP-Sensitive K+ Channels.
- Plasma membrane depolarized
- Ca+ channels opened and it floods in. This triggers the release of insulin by exocytosis.
23
Q
B-Cell ATP-sensitive K+ channels have what special subunits?
A
- Sulfonylurea receptor (SUR)
- Activated by sulfonylureas
- which are used to treat Type 2 diabetes mellitus.
- Activated by sulfonylureas
24
Q
What is the role of incretins and what are the two good canidates for this at physiological conditions?
A
-
Incretins: hormones released by cells in the intestinal mucosa that promotes glucose stimulated insulin release.
- Responsible for about half of insulin release.
- Candidates:
- GIP
- GLP-1
25
What inhibits insulin release by **sympathetic stimulation?**
**Exercise** and **Stress**
26
How do Stress and Exercise inhibit insulin release?
**Sympathetic Stimulation**
27
What is the **most important physiological stimulus** for the release of glucagon?
And what two conditions cause this?
**Hypoglycemia**
**Stress** and **exercise.**
28
What is BMR and how may it be measured both directly or indirectly?
* Basal Metabolic Rate
* Directly: **Heat Production**
* Indirectly: **Oxygen consumption**
29
What is an example of another hormone besides insulin and glucagon that also effects the mobilization and utilization of nutrients?
* **Thyroid Hormones**
* ****T4: Inactive form
* T3: Active form
* Increase in T3 in bloodstream, increases **BMR**
* **Epinephrine**
* Promotes glucose release by the liver and stimulates lipolysis.
30
What is the absorptive state?
Period of time during and after the ingestion of a meal when cell metabolism is fueled primarily by the nutrients absorved from that meal.
31
Where does **Carbohydrate metabolism** occur duing the **absorptive state?**
**Liver**
32
What does **insulin-to-glucagon ratio** help indicate?
**It is an important determinant of hepatic function.**
33
What does **GLUT2** do? and how?
* It is a **bidirectional transporter**, with a **low affinity for glucose.**
* **Absorptive State**: Glucose enters liver cells due to elevated glucose levels in the portal vein.
* **When plasma glucose levels are low**: GLUT2 limits entry into liver cells.
* **When hepatic glucose production is stimulated**: Glucose exits the GLUT2 transporter.
34
When glucose enters the liver it is converted to _____ by \_\_\_\_\_\_\_.
Glucose 6-phosphate
## Footnote
**Glucokinase**
35
What hormone increases glucokinase expression?
**Insulin**
36
When fasting why is glucose not converted to G6P.
* **Glucose is spared for use by other tissues during interdigestive periods**
37
What role does **insulin** have in the liver?
* **Promotes storage of glucose as glycogen**
* **Promotes glycolysis**
* **Promotes FA synthesis**
* **Inhibits:**
* **Release of Glucose******
* ******Glycogenolysis**
* **Gluconeogenesis**
38
How does insulin promote glycolysis in the liver?
* Pyruvate -\> Acetyl CoA
* Acetyl CoA is **oxidized** via the TCA cycle.
* High glucose levels = Acetyl CoA used for FA synthesis.
39
How does insulin inhibit release of glucose in the liver?
**Repressing the expression** of the gene for **G6P**.
40
How does insulin inhibit gluconeogenesis in the liver?
**Inhibit protein catabolism**
41
Liver glycogen levels peak ______ after the ingestion of a meal
4 to 6 hours
42
How does the liver change in response to a change in the composition of ones diet?
* High in carbohydrate = produce more enzymes for carb metabolization and fat synthesis.
* High Protein Content = produce more enzymes for amino acid metabolism and gluconeogenesis.
43
How does insulin promote glucose uptake in skeletal muscle?
* By stimulating the **translocation of GLUT4**
* **Exercise** also does this.
44
Can glycogen in skeletal muscle be used to maintain blood glucose levels? Detail?
* No it cannot assit.
* Skeletal muscle lacks **Glucose 6-Phosphatase.**
45
Describe Lipid Metabolism during the Absorptive State?
* **FA** are converted by **chylomicrons** into **TAGs.**
46
What role does insulin play in lipid metabolism?
Insulin induces the synthesis and secretion of Lipoprotein lipase (LPL).
47
What does lipoprotein lipase do?
It **catalyzes** the **breakdown** of **Triacylglycerols** into **VLDLs to monoglycerides & fatty acids.**
48
Insulin inhibits _____ in fat cells by acting \_\_\_\_\_\_\_\_\_\_.
**basal and hormone-stimulated lipolysis**
**Hormone-sensitive lipase**
49
What catalyzes the breakdown of intracellular TAGs to fatty acids and glycerols?
Hormone-sensitve Lipases
50
In the liver, Insulin surpresses \_\_\_\_\_\_, since the liver is the principle provider of ______ bodies.
Ketogenesis
Ketone
51
How does insulin supress ketogenesis?
* Decreasing the flow of fatty acids to the liver
* Stimulates the **malonyl CoA** which **blocks FA transport into the mitochondria.**
52
Ketone Disorder?
**Ketosis**
53
The liver is the primary site of _____ FA synthesis
De novo
54
In skeletal muscle insulin stimulates?
* Amino acid uptake and protein synthesis.
* Inhibits Proteolysis of muscle.
55
Liver is the primary source of _____ during a fast.
What is the process called and where else can it occur?
* Glucose
* Gluconeogenesis
* Kidneys.
56
What role does **glucagon** play in the liver during a fast?
Stimulates glycogenolysis and inhibits glycogen synthase.
57
Peripheral regulation of gluconeogenesis involves?
* Cortisol: Promotes protein catabolism
* Insulin: inhibits protein catabolism
58
During the first 3 days to a fast:
* Blood glucose & insulin decreases
* Blood glucagon increases
*
59
After about 3 days of fasting:
* Plasma glucose, FFA, and glycerol stabilize.
* Ketones level continue to increase.
* Growth hormone levels increase.
60
During a prolonged fast:
* Drop in BMR
* Decreased Thyroid activity.
* T4 is same; T3 is lower.
* Reflects decrease in peripheral conversion of T4 to T3.
* **Brain begins using ketones.**
* **Spares proteins.**
61
How is Hypoglycemia regulated?
* When: Blood glucose drops
* Hypothalmus activates the sympathetic NS
* Stimulates glucagon release and inhibit insulin relase .
* Epinephrine: inhibits glucose utility by muscle
* Stimulating Glycogenolysis and gluconeogenesis.
62
What is the primary counter regulator in restoring blood glucose levels.
Glucagon.
63
How quick do glucagon and epinephrine elicit responses?
Very rapid; provide minute-to-minute regulation.
64
How does the pituitary help with hypoglycemia?
* Releases GH and ACTH
* ACTH stimulates cortisol
* Promotes gluconeogenesis and blocks glucose uptake by certain peripheral tissues.
65
What is neuroglycopenia?
Deficient supply of gluocse in the CNS
66
What is the "Satiety center"
Ventromedial nucleus
67
What is the "hunger center"?
Lateral Hypothalamus
68
What are the two neuronal groups that activate the arcuate nucleus of the hypothalmus.
* POMC/CART neurons
* NPY/AgRP -secreting neurons.
69
What do POMC/CART neurons release and what is the effect?
* Release **a-MSH** (aka, **melanocortin**)
* Decrease food intake
* increase in energy expenditure
70
What do NPY/AgRP -secreting neurons release and what is the effect?
* Neuropeptide Y (NPY):
* Promotes feeding behavior
* Reduce energy expenditure
* AgRP:
* antagonist that competes with a-MSH for binding on melanocortin receptors.
71
As the mass of adipose tissue increases, _____ release also increases.
Leptin
72
What role does leptin have?
* Inhibits: NPY and AgRP
* Stimulates: a-MSH
Net effect: Decrease food intake, increase energy expenditure.
73
What does Ghrelin do?
Stimulates appetite.
74
What is the role of PPY3-36
Appetite surpressant
75
PPY3-36 disorders?
PYY3-36 crosses the BBB and can lead to anorexic effects.
76
