Ch. 20 Obesity and Diabetes Flashcards
1
Q
Anabolism
A
Synthesis of new molecules (require energy)
2
Q
Catabolism
A
Breakdown of large molecules (makes energy)
3
Q
Energy of Carbohydrates
A
4 kcal/g
4
Q
Energy of protein
A
4 kcal/g
5
Q
Energy of fat
A
9 kcal/g
6
Q
Alcohol
A
7 kcal/g
7
Q
Basal Metabolic Rate
A
Body’s vital energy needs during physical, emotional, and digestive rests
8
Q
Syndromes that BMR increases
A
Hyperthyroidism, fever, Cushing’s syndrome, tumor of adrenal gland, anemia, leukemia, polycythemia, cardiac insufficiency, injury
9
Q
Syndromes the BMR decreases
A
Hypothyroidism, starvation, malnutrition, hypopituitarism, hypoadrenalism, anorexia nervosa
10
Q
Hypothalamus’ role in feeding behavior
A
Integration of signals for energy storage and dissipation
11
Q
AMPK
A
AMP-activated protein kinase Metabolic switch in cell High [AMP]->Activate AMPK->ATP synthesis Phosphocreatine + glycogen ->negative allosteric regulator
12
Q
Metformin does_______
A
Activates AMPK->ATP synthase->decrease glucose concentration
13
Q
What is the purpose of leptin?
A
Long-term regulator that regulates size (not #) of adipose tissue & energy balance Tells you that you are “full” (decrease appetite)
14
Q
Where is leptin made?
A
Adipocytes
15
Q
Positive regulators of leptin (causes increased secretion of leptin)
A
Insulin, glucocorticoids, estrogens, well-fed state (expansion of fat stores)
16
Q
Negative regulators of leptin (causes decreased secretion of leptin)
A
B-adrenergic agonists, starvation (depletion of fat stores)
17
Q
What is the function of PPAR-Gamma2
A
Peroxisomal proliferator activating receptor Regulates conversion of preadipocytes to adipocytes Stimulates leptin which negatively feedbacks to PPAR-gamma2
18
Q
What is the function of Thiaxolidinedione?
A
Activate PPAR-gamma2
19
Q
Pathway of leptin during starvation
A
[Low leptin]->produce neuropeptide Y from hypothalamus->transport to PVN paraventricular nucleus)-> increase appetite & parasym activity & Decrease expenditure, temp, reproductive function
20
Q
Pathway of leptin during well-fed state
A
[High leptin]->MSH bind to MC4-R-> Decrease appetite, increase energy expenditure and sympathetic system
21
Q
Overweight BMI range
A
25-29.9
22
Q
Obese BMI range
A
>30
23
Q
What can cause early onset obesity?
A
Congenital human leptin deficiency Defective leptin receptor
24
Q
What is the enigma in obese people?
A
They have high [leptin] due to increased adipose tissue (which means that they should be full), but maybe they are resistant to leptin
25
Prader-Willi Syndrome
Most prevalent form of dysmorphic genetic obesity Absence of PATERNAL PWS/AS region of Ch. 15
26
Angleman Syndrome
Inherited MATERNAL Chromosome 15 deletions
27
What does skeletal muscle use to maintain cellular integrity during rest?
Fatty acid catabolism and Branched Chain Fatty Acids
28
What does skeletal muscle use as a main source of energy when exercising?
Initially uses glycogen stores After depleted, FA provide mobilization of TAG from adipose and that becomes dominant source
29
How much does the O2 consumption of skeletal muscle increase when going from rest to exercise?
30 fold (30% of body's O2 consumption to 90%) Need to use anaerobic glycolysis
30
How is low-level non-fatiguing exercise different from high-intensity endurance exercise?
Low-level non-fatiguing doesn't have depletion of Phosphocreatine and has minimal use of glycogen utilization Main source of energy in Low-level: aerobic oxidation of FA, glucose, and BCAA
31
Define metabolic homeostasis
Tendency for biological systems to maintain relatively constant chemical conditions in internal environment. It's regulated by endocrine system
32
What are the 3 main functions of the major fuels (CHO, lipids, protein)
Maintain blood glucose level in narrow limits Maintain optimal glycogen supply Maintain optimal protein supply
33
What are the 3 main ways to regulate body weight?
Food intake, heat loss, and exercise (energy expenditure)
34
What are the metabolic roles of the liver?
1. 1st to receive nutrients from intestines (except lipids..go to lymphatic system) and also tastes insulin and glucagon
2. Deliver bile into intestines (cholesterol homeostasis)
3. Primary site of glycogen deposition and glucose maintenance
4. Lipid, protein, and nitrogen homeostasis
35
What is the main energy supply of the liver?
Fatty acid oxidation
36
What are the functions of brown and white adipose tissue?
Brown: production of heat
White: TG for export as fatty acids
37
Carbohydrate and Fat Metabolism in adipose tissue
Adipose tissue glucose transport sensitive to insulin levels (more insulin, more absorption)--\> increased glycolysis where glycerol phosphate used for TAG synthesis.
Fat metabolism: Fatty meal-\>hyrolysis of TAG from chylomicrons and VLDL via LPL-\>supply liver with FA
Adipocytes lack glycerol kinase, so G3P used in TAG synthesis comes from glucose metabolism
38
What energy supply does adipose tissue use?
FA oxidation and TCA cycle
39
Why can't skeletal muscle be a source of blood glucose?
Lacks G6Pase
40
What does the muscle provide during starvation?
During 1-2 weeks, muscle uses FA from adipose and ketone bodies from liver as fuel. After 3 weeks, muscle decreases use of ketone bodies and only oxidizes FA
41
How much of the body's oxygen does the brain use?
20%; 2/3 of it is used to maintain transmembrane potential
42
What does the heart use for fuel?
Heart known as SCAVENGER. will use anything: fatty acids, ketone bodies, lactate, pyruvate
43
What do the kidneys use for energy?
Glucose, fatty acids, ketone bodies, amino acids
44
What is the role of albumin?
Most abundant plasma protein. Used for osmotic regulation, transport of FA, drugs, toxic metabolites, and indicator of hepatic function
45
What is the formula for insulin?
C257 H383 N65 O77 S6
46
Describe the structure of insulin
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51 amino acids; A and B chain linked by 2 disulfide bridges, C peptide
47
What is Lispro insulin?
Lys and Pro location switched at position 28 /29-\>no dimer formation-\>works faster than normal-\>insulin of choice for diabetes
48
Synthesis of insulin
1. Transcribe insulin genes to mRNA
2. In cytoplasm, translate mRNA on cytosolic ribosome
3. N-terminal signal peptide penetrates RER + elongation
4. Preproinsulin formed
5. Signal peptide cleaved to form proinsulin (in lumen of RER)
6. Proinsulin transported to golgi and forms C-peptide and insulin
7. Insulin and C peptide packed into secretory granules
8. Secretory granules released
49
Familial hyperproinsulinemia
Autosomal dominant; deficiency in proinsulin receptor or abnormal proinsulin
50
What stimulates the secretion of insulin?
1. Glucose (has GLUT 2 transporters and glucokinase activity)
2. Amino acids (eat protein causes rise in plasma a.a. levels)
3. Gastrointestinal hormones (CCK and gastric-inhibitory polypeptide are incretins) released from small intestine after ingestion and cause anticipatory rise in insulin
4. ACh
5. SUR (sulfonurea receptor)
6. Beta-adrenergic agents
7. Glucagon-like peptide (???)
51
What inhbits insulin secretion?
1. Scarcity of dietary fuels
2. Stress (fever, infection) - adrenal medulla releases epinephrine
3. Somatostatin
4. alpha-adrenergic agents
5. diazoxides
52
Hyperinsulinism-Hyper ammonemia
Hyperinsulinism: Too much insulin; defective glutamate dehydrogenase
Hyperammonemia: constantly convert Glu-\>aKG which generates NH3+
53
MODY
Maturity onset diabetes young: glucokinase deficiency
54
Biological actions of insulin
Promote fuel storage (glycogen synthesis in liver and muscle)
Glucose uptake into muscle and adipose tissue via GLUT 4
In liver, inhibits gluconeogenesis and glycogenolysis (production of glucose)
Inhibit hormone sensitive lipase in adipose (inhibit TAG breakdown)
Increased TAG synthesis (import glucose into adipocytes-substrate glycerol 3 phosphate used for TAG syn)
Promote entry of amino acids into cells and protein synthesis
55
Insulin Receptor
Heterotetramer (alpha/beta subunits linked by disulfide bonds)
Alpha subunit used for binding (extracellular), Beta is hydrophobic tyrosine kinase (activated by insulin)
56
How does insulin promote glucose influx into cell?
1. Insulin binds to receptor
2. Activated receptor autophosphorylates B subunit (tyrosine kinase) and cascade promotes recruitment of glucose transporters to membrane
3. Glucose transporters increase insulin-mediated uptake of glucose (GLUT 4)
4. When insulin levels decrease, glucose transporters move from membrane to inside cell and recycled
57
What are the 3 ways to release insulin? One way to inhbit release?
1. Glucose
1. Glucose binds to GLUT 1/2, converted to G6P, make ATP, depolarize membrane potential, open Ca channels, Ca enters, promotes release of insulin
2. ACh
1. Activate Gq, Phospholipase C converts PIP into IP3 and DAG, IP3 causes ER to release more Ca (causing release of insulin) and DAG activates Protein Kinase C and uses Ca to release insulin
3. GLP-1
1. Activate Gs, adenylate cyclase, cAMP, Protein Kinase A, release insulin
4. Inhibit: Norepinephrine
1. Activate Gi, inhibit adenylate cyclase
58
What other function does Ca have in relation to insulin?
Besides actually causing release of insulin granules, Ca increases the expression of the insulin gene via CREBP (cyclic AMP response element binding protein)
59
What cells are insulin, glucagon, and somatostatin released from?
Insulin: Beta cell, Glucagon: Alpha Cell, Somatostatin: Delta cell
60
Main functions of glucagon
Maintain blood glucose levels by activation of hepatic glycogenolysis, gluconeogenesis, & ketogenesis
Inhibit glycogenesis
Enhance lipolysis of TG in adipocytes to provide FFA
61
What stimulates glucagon secretion?
1. Low blood glucose: Main driver of glucagon secretion
2. Amino acids: triggers release of insulin AND glucagon (prevents hypoglycemia that would be caused by insulin)
3. Epinephrine: during stress (can override other effects and still increase blood glucose level in anticipation of increased glucose use)
62
What inhbits glucagon secretion?
Elevated blood glucose levels adn insulin
63
Glucagon MOA
1. Binds to receptor on hepatocyte
2. G protein complex
3. Adenylyl cylcase
4. Increase in cAMP
5. cAMP-dependent protein kinase
6. Increase phosphorylation of enzymes and other proteins used for things like glycogen degradation
64
What are the 2 forms of somatostatin and where is it synthesized?
S14 and S28
Delta cells of islets, gut, hypothalamus, and several other areas in brain
65
Functions of somatostatin?
In islets: block insulin and glucagon secretion
In pituitary gland: inhibit GH and TSH release
In gut: block gastrin and motilin secretion-\>inhibit gastric acid and pepsin secretion,suppress gallbladder contraction-\> decreased delivery of nutrients to system
66
What is pancreatic polypeptide?
36 a.a. secreted in response to fuel ingestion and can potentially affect pancreatic exocrine secretion of HCO3 and protein
67
When does the brain, RBC, and skeletal muscle use glucose vs. FA?
Brain/other nervous tissue: use glucose normally; FA only in long-term fasting
RBC: only anaerobic glycolysis-\>lactate
Skeletal muscle: FA at rest; Glucose/glycogen (if available) during exercise
68
What factors influence the blood glucose profile?
1. Digestion and absorption of carbohydrates are rapid
2. Rise in blood glucose followed by rise in insulin
3. Concomitant changes in glucagon release depend on diet (high carb=low glucagon; high protein=high glucagon release)
4. Liver freely permeable to glucose and extracts about 50% of CHO load
5. Liver converts excess glucose to TG -\> VLDL
6. Glucose not sequestered by liver
7. Insulin stimulates uptake of glucose into muscle by GLUT 4
8. Glucose taken up by adipocytes under influence of insulin
9. Insulin directly stimulates glucose uptake by most cells (except brain, liver, blood cells)
69
Stimulation and Inhibition of glycogen synthase
1. Insulin activates glycogen synthase
2. G6P allosterically activates glycogen synthase
3. Absend syence of cAMP-\>block cAMP-dependent protein kinase-\>inactivate glycogen synthase
4. Glycogen stores high-\>inhibit glycogen synthase phosphatase-\>end synthesis of glycogen
70
What does it mean to be glucose intolerant?
Unable to clear glucose from blood in appropriate time (takes longer) and blood glucose level shoots past normal level
71
How is hepatic glycogen used?
Glucagon stimulates glycogenolysis via adeylate cyclase cascade
Catecholamines released during high stress stimulate Ca release from ER + allosteric activation of phosphorylase kinase
72
How is skeletal muscle glycogen used?
Muscle lacks G6Pase so can't release glucose into blood. Instead turn muscle glycogen-\>lactate-\>glucose in liver
73
How is skeletal muscle glycogen utilization regulated?
ADP required for glycolysis
Phosphofructokinase (PFK) catalyzes irreversible step and subject to allosteric inhibition
Skeletal muscle phosphorylase b is allosterically regulated
74
What are the 4 sources for gluconeogenesis?
Glycerol, lactate, amino acids, and propionate
75
How is gluconeogenesis regulated?
Glucagon (acute modulator), glucocorticoid (chronic modulator), and absence of insulin
76
What are the sources of carbon for hepatic glucose formation?
Hepatic glycogen, lactate from RBC or skeletal muscle, a.a. from muscle protein, glycerol from adipocytes
77
What actions does glucagon trigger?
(NEED ENERGY) Glycogen breakdown, gluconeogenesis,TG hydrolysis, and FA oxidation
78
What actions does insulin trigger?
(STORE ENERGY): Glycogenesis, glycolysis, FA synthesis
79
What actions do glucocorticoids stimulate?
FA oxidation, gluconeogenesis, glycogenesis, increase enzymes of glucagon action
80
Describe the pathway of exogenous lipid digestion and absorption
Dietary lipid mostly TG-\>break down to FA-\>reorganized into TG-\>form chylomicron-\>lymphatic capillaries-\> systemic circulation, postalimentary lipemia (fat in blood)
81
Explain interaction between chylomicrons and LPL
Chylomicron's TG digested by LPL secreted by adipocytes, hepatocytes, and cardiac/mammary tissue -\> hydrolyzed into FA
82
Carbohydrates to TGs
Dietary CHO-\>TG in adipocytes or hepatocytes-\>VLDL-\>transport to adipocytes
83
Release of lipid from adipose tissue
During fasting/exercise/stress, lipids used for energy. Hormone-sensitive lipase catalyzes sequential hydrolysis of TAG to yield 3 FA + 1 glycerol\* (regulated by cAMP dependent kinase)
\*Different from pancreatic lipase: 2 FA + 1monoacylglycerol
84
Hormonal regulation of adipocyte lipolysis: Rapid stimulators
Epinephrine, norepinephrine, glucagon, ACTH, secretin, vasopressin
Release FFA within minutes
85
Hormonal regulation of adipocyte lipolysis: Slow stimulators
Glucocorticoids, growth hormone
Release FFAs within hours
86
Hormonal regulation of adipocyte lipolysis: Inhibitors
Insulin, prostagland E1 (suppress by depressing cAMP levels)
87
Except _____ and ____ cells, tissues can use FAs by b-oxidation and TCA cycle.
Nerve and blood cells
88
How do FA get into cells?
Free diffusion (not regulated)
89
What cofactors are required for FA synthesis?
NAD, FAD, and ADP
90
Purines made from
Glycine, aspartate, glutamine
91
Pyrimidines made from
Aspartate, glutatmine
92
Porphyrins made from
Glycine
93
Polyamines made from
Arginiine, methionine
94
Creatine made from
Arginine, glycine
95
Serotonin, melatonin made form
tryptophan
96
Catecholamines, dopamine, melanin made fom
Tyrosine
97
Histamine made from
Histidine
98
Nitric oxide made from
Arginine, citrulline
99
