Week 5 Flashcards
1
Q
What is metabolism?
A
Sum of all chemical reactions in a body
2
Q
Anabolic
A
large molecules synthesised from smaller ones
3
Q
Catabolic
A
Breakdown of larger molecules into smaller ones
4
Q
What are the two states?
A
Fed (absorptive) and Fasted (postabsorptive)
5
Q
Fed state
A
anabolic state
Uses glucose for energy
6
Q
Fasted state
A
catabolic, uses glucose, fat for energy
7
Q
Basal Metabolic rate (BMR)
A
An individual’s energy expenditure when resting, comfortable temperature, fasted
8
Q
Energy balance
A
we control caloric intake and exercise
9
Q
Glycogenolysis
A
Breakdown of glycogen from liver and muscle to glucose
10
Q
Glycogenesis
A
creation of glycogen from glucose
11
Q
Glycolysis
A
the breakdown of glucose releasing ATP (energy and pyruvic acid)
12
Q
what does glycolysis occur along with ?
A
tricarboxylic acid cyle and oxidative phosphorylation
13
Q
Lipogenesis
A
fatty acid and glycerol to triglycerides (adipose tissue)
14
Q
Lipolysis
A
break down of trigylcerides to fatty acids and glycerol
15
Q
what happens when fatty acid and glycerol breakdown ?
A
beta oxidation of FFA, releases ATP
16
Q
Protein synthesis
A
amino acids to protein (muscle)
17
Q
Protein degradation
A
protein to amino acids
18
Q
Gluconeogenesis
A
synthesis of glucose from non-carbohydrate substrates such as glycerol and amino acids
19
Q
How does glucose get inside cells?
A
Glucose transporters (there are 14 different types)
20
Q
2 main types of glucose transporters that were are focusing on?
A
GLUT 2 and GLUT 4
21
Q
GLUT 2
A
Liver, Pancreas (intestines, kidneys)
Glucose transport and insulin secretion
22
Q
GLUT 4
A
Adipose tissue, skeletal muscle
Glucose transport (insulin dependent)
23
Q
what does beta cells in the pancreas contain and release?
A
it contains proinsulin, it releases insulin+c peptide
24
Q
what do alpha cells in pancreas release?
A
glucagon
25
what do delta cells in pancreas release ?
somatostatin
26
exocrine (acinar cells) of the pancreas
contain zymogens
The produce bicarbonates and proenzymes that are used for digestion
27
islet of Langerhans
cluster of cells in the pancreas (alpha, beta, delta epsilon) that release different hormones
28
glucagon and glucose
opposing actions
Glucagon increases when glucose is lowered
29
insulin and glucose
same action
insulin gets lowered when glucose is lowered
30
insulin
the dominant hormone of the fed state, it is synthesized as a typical peptide
31
what receptor does insulin bind to?
tyrosine kinase
32
what does insulin do?
it helps reduce blood glucose and promotes the formation of glycogen, fat, and protein
33
Mechanisms of insulin action
1. Insulin binds to tyrosine kinase receptor
2. Receptor phosphorylates insulin-receptor substrates (IRS)
3. Second messenger pathways alter protein synthesis and existing proteins
4. membrane transport is modified
5. Cell catabolism is changed
33
Low insulin/glucagon ratio
fasted
34
High insulin/glucagon ratio
fed
35
Insulin and Glucose transport in liver through GLUT2
Liver expresses GLUT2 transporter on the plasma membrane (independent of insulin)
35
what happens when there is a high insulin/glucagon ratio?
1. Insulin binds to the receptor.
2. Signal transduction cascade.
3. exocytosis of GLUT 4 onto the plasma membrane
4. glucose enters cell from bloodstream
36
GLUT2 mechanism
In the fed state, Insulin activates hexokinase maintaining a high glucose concentration gradient which indirectly increases glucose uptake by the liver.
37
Intravenous v/s intrajejunal glucose infusion
intrajejunal causes a much HIGHER increase in insulin after the addition of glucose
38
Incretin effect
the difference in plasma insulin after intravenous and intrajejunal glucose addition.
higher plasma insulin for intrajejunal
38
What does hexokinase help with?
Hexokinase-mediated conversion of glucose to glucose 6-phosphate keep intracellular (glucose) low
39
Insulin release mechanism
1. Increase of glucose in the blood
2. glucose will enter beta cell through GLUT
3. Increase in glycolysis and citric acid cycle
4. Increase in ATP
5. the potassium channels close
6. Less K+ leaves the cell
7. cell depolarizes
8. Ca2+ channel opens
9. Ca2+ entry triggers exocytosis and insulin is released
40
what was GIP-1 previously known as?
Gastric inhibitory peptide
40
Incretin hormones
GIP-1 (Glucose-dependent Insulinotropic polypeptide) and GLP-1 (Glucagon-Like peptide)
41
What does glucagon do?
Increases glycogenolysis, gluconeogenesis, and ketogenesis.
it prevents hypoglycemia.
41
what releases GLP-1?
It is released by L cells in the small and large intestine in response to nutrients in the intestinal lumen.
GLP-1 Receptor (GPCR, Gas) on beta cells to stimulate insulin release.
41
what releases GIP-1?
it is released by K cells in the small intestine in response to nutrients in the intestinal lumen.
GIP-1 Receptor (GPCR, Gas) on beta cells to stimulate insulin release.
41
Mechanism of GLP-1
1. GLP-1 binds to the GLP-1 receptor
2. the G alpha S subunit is activated
3. adenylate cyclate is released, that releases cAMP
4. cAMP will activate EPAC (exchange protein activated by cAMP)
5. insulin is released from beta cell
this work in conjunction with Ca2+ mechanism
42
Stimulation of insulin secretion
1. increase in plasma glucose
2. Intestinal (incretin) hormones such as GLP-1 and GIP-1, both releases in response to nutrient ingestion=feedforward regulation
3. increased plasma amino acids
4. parasympathetic nervous system - rest and digest
43
inhibition of insulin secretion
1. sympathetic nervoud system- fight/flight
43
what does glucagon target?
liver
44
in what state does glucagon dominate?
fasted
45
mechanism of glucagon
in reponse to fasting, glucagon triggers the activation of a cascade of signalling molecules inside the hepatocytes, each transmitting and amplifying the fastest signal.
it promotes the transport of glucose out of hepatocytes through GLUT2
46
what is there inside hepatocytes
glycogen stores and glconeogenesis
47
What is needed for the full activity of glucagon and epinephrine?
cortisol
48
Stimulation of glucagon secretion
1. decreased plasma glucose
2. increased plasma amino acids
3. sympathetic nervous system
49
what three hormones does proglucagon contain
glucagon, GLP-1, GLP-2
49
inhibition of glucagon secretion
1. glucagon-like peptide-1 (GLP-1)
50
where is proglucagon expressed
alpha cells, L cells on intestine and brain
51
The main product in alpha cells
glucagon
52
The main product in L cells of the intestine and brain
GLP-1 and GLP-2
53
Key points- insulin
Insulin (prevents hyperglycemia): Beta cells (islet of Langerhans) – secreted in response to glucose, GLP1, PNS, amino acids – decreases blood glucose, promotes anabolic pathways, involved with growth
54
Key points - GLP-1
released from intestine in response to glucose/amino acids – stimulates insulin secretion, increases beta cell mass, anorexigen, decreases glucagon
55
Key points- Glucagon
Glucagon (prevents hypoglycemia):Alpha cells secrete
Glucagon in response from low glucose, SNS, amino acids
– increases blood glucose, gluconeogensis, glycogenolysis
– catabolic pathways to increase energy.
56
Type-1 Diabetes
Insulin dependent diabetes- juvenile
-10%
-Insulin secretion reduced or absent
- treated by insulin injections or pumps
57
Type 2 diabetes
Non-insulin dependent diabetes, mature onset
- 90%
- Defect in insulin secretion and target cells responsiveness to insulin is reduced.
- treated by diet, exercise, (translocation of GLUT4 to membrane), oral hypoglycemic (Sulfonylurea, GLP1)
58
Actions of GLP-1 as medication
reduces inflammation, myocardial infarction, atheroscleoris, diabetic kidney disease, metabolic liver disease
59
What is the posterior pituitary?
Neural tissue; extension of the brain that secretes neurohormones made in the hypothalamus.
60
what is the anterior pituitary?
true endocrine gland
61
2 hormones released by posterior pituitary
vasopressin and oxytocin
62
6 hormones secreted by the anterior pituitary
prolactin, thyrotropin. adrenocorticotropin, growth hormone, follicle-stimulating hormone, luteinizing hormone
63
Stalk connecting posterior pituitary and hypothalamus
infundibulum
64
How to hypothalamic hormones reach the anterior pituitary?
portal system
65
Inhibitor of prolactin
dopamine (PIH)
66
Hypothalamic releasing hormone and inhibiting hormone of growth hormone/somatotropin
Hypothalamic releasing hormone- GHRH
Hypothalamic releasing hormone-Somatostatin (Growth hormone inhibiting hormone)
67
The trend seen for bone mass
Decreasing bone mass with age
68
Bones: Adult
Growth plates closed
Bone loss >40 years
68
Bones: adolescent
Bones fully ossified
Growth plates closing towards end of puberty
69
Bones: in-utero
Cartilage not fully ossified
Active growth plates
69
Mechanism of growing bones
1. Osteoblasts lay down on top of bone cartilage
2. Old chondrocytes disintegrate
3. Chrondocytes produce cartilage, causing the epiphyseal plate to widen
4. Diving chronodocytes add length to bone
70
Chrondocytes
They produce cartialge
71
What does IGF-1 do?
Increase recruitment, proliferation, and matrix of chondrocytes.
72
Where does growth hormone act and what does it stimulate?
It acts in the liver to stimulate IGF (Insulin-like growth factors) release
73
Receptor for growth hormone
tyrosine kinase
74
Glucose sparing effect: Catabolic action of GH
ulates adipose cells to breakdown stored fat, fueling growth effects
75
Growth effect: catabolic action of GH
1. Increases uptake of amino acids from blood.
2. Enhances cellular proliferation and reduces apoptosis
76
Diabetogenic effect_ Catabolic effects of GH
GH stimulates the liver to break glycogen into glucose, fueling growth effects. It also stimulates IGF1 release which stimulates growth effects.
77
Age (Thyroid hormones)
Early years and puberty
78
Age (growth hormone)
More or less consistent, decreases after 16
79
Androgens and estrogens
Peak during puberty
80
Gigantism
Too much growth hormone is childhood
81
Acromegaly
Too much GH in adulthood - long bones fuse together, thickening at the end of bones
82
Parts of thyroid gland
C cell, Follicular cells, capillary, colloid
83
What are thyroid hormones made from?
Iodine and tyrosine
84
How are thyroid hormones made
1. A Na+-I- symporter brings I- into the cell. the pendrin transported moves I- into the colloid.
2. Follicular cells synthesizes enzymes and thyroglobulin for colloid.
3. Thyroid peroxidase adds iodine to tyrosine to make T3 and T4.
4. Throglobulin is taken back into the cell by vesicles.
5. Intracellular enzymes separate T3 and T4 from the protein.
6. free T3 and T4 enter circulation.
85
T3
MIT+DIT
86
T4
DIT +DIT
87
What does TSH do?
Activates G protein-linked membrane receptors acting via adenylate cyclase. Stimulates the synthesis and activity of enzymes T3 and T4. Activates transcription factors c-fos and c-myc
Stimulates thyroid growth.
88
Mechanism of action of thyroid hormones
T3 and T4 circulate in blood bound to plasma proteins.
Both bind to nuclear thyroid receptors ( form homodimers or heterodimers with retinoic acid receptors)
89
What is more potent: T3 or T4?
T3 (3-5X)
T4 is converted to T3 in target tissues
90
Functions of thyroid hormones
1. metabolic (metabolic rate, oxygen consumption, heat production, protein degradation, lipolysis)
2. nervous system (enhances speech, thinking, reflexes)
3. Growth and development (essential in children, works with GH)
4. Cardiovascular (enhances heart rate and contractility; peripheral blood flow, works in part by increasing the number of beta-adrenergic receptors + other proteins.)
5. Muscular (too much causes muscle weakness)
91
causes of hyperthyroidism
tumors
thyroid-stimulating immunoglobulins (Grave's disease)
92
Symptoms of hyperthyroidism
goiter, nervousness, insomnia, anxiety, weight loss, high heart rate, exophthalmos
93
Grave's disease
autoimmune disease: abnormal antibodies against the TSH receptor are produced. =
94
Causes of hypothyroidism
1. under active throid gland
2. iodine deifiency
95
Symptoms of hypothroidism
goiter, slowed heart rate, slowed speech, fatigue, cold-intolerance, cretinism (infants), stunted growth (infants), weight gain
96
iodine deficiency
1. leaves thyorid gland uanble to produce T3 and T4
2. Lack of negative regulation leads to excess TSH secretion
3. TSH stimulates growth of thyroid gland, goiter may be present
