Ch. 20: Perturbations Of Energy Metabolism: Obesity & DM Flashcards

1
Q

What is anabolism?

A

Synthesis of new molecules (requires energy)

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2
Q

What is catabolism?

A

Breakdown of large molecules ➡️ smaller ones (yields energy)

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3
Q

What is intermediary metabolism?

A

All changes in a food substance from absorption ➡️ excretion

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4
Q

How many kcal/g are there in: Carbs? Protein? Fat? Alcohol?

A

Carb: 4 kcal/g
Protein: 4 kcal/g
Fat: 9 kcal/g
Alcohol: 7 kcal/g

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5
Q

What is basal metabolic rate (BMR)?

A

Vital energy needs of the body during physical, emotional, and digestive rests

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6
Q

In what situations is BMR ⬆️?

A

Hyperthyroidism, fever, Cushing’s syndrome, adrenal tumors, anemia, leukemia, polycythmia, cardiac insufficiency, injury

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7
Q

In what situations is BMR ⬇️?

A

Hypothyroidism, starvation, malnutrition, hypopituitarism, hypoadrenalism (Addison’s), anorexia nervosa

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8
Q

What is the role of the hypothalamus in mediating feeding behavior?

A

Integrates signals for energy storage & dissipation

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9
Q

What is the structure of AMP-activated protein kinase (AMPK)?

A

Heterotrimeric protein complex:

1) Catalytic alpha-subunit
2) Regulatory beta & gamma subunits

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10
Q

How is AMPK activated? Function?

A

⬆️ [AMP]/ATP ➡️ ➕ AMPK ➡️ ATP synthesis

AMPK also ➕ by: Metformin, Troglitazone, LKB1, CaMKKbeta, other kinases

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11
Q

What are the negative allosteric regulators of AMPK?

A

Phosphocreatine

Glycogen

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12
Q

What does AMPK activate?

A

1) p53 ➡️ ⬆️ cell cycle arrest ⬇️ cancer risk
2) TSC2 ➡️ ➖ mTOR ➡️ ⬇️ protein synthesis/cell survival
3) EF2K ➡️ ⬇️ protein synthesis

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13
Q

What does AMPK inhibit?

A

1) ACC1/FAS ➡️ ⬇️ FA synthesis
2) ACC2 ➡️ ⬆️ FA oxidation
3) HMG-CoA reductase ➡️ ⬇️ sterol synthesis

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14
Q

What is leptin? Function?

A

Long term regulator of energy metabolism, hunger & satiety

Acts in afferent signal pathway of negative feedback loop ➡️ regulate size of adipose tissue & energy balance

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15
Q

What cells synthesize leptin?

What ⬆️ leptin synthesis? ⬇️ leptin synthesis?

A

Adipocytes

⬆️ leptin synthesis: insulin, glucocorticoids, estrogens
⬇️ leptin synthesis: beta-adrenergic agonists

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16
Q

What does leptin inhibit? What is its function as a regulator?

A

PPAR-gama2: regulates conversion of preadipocyte to adipocytes ➡️ ⬇️ blood glucose

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17
Q

Why do obese individuals have ⬆️ leptin levels?

A

Resistance/defect in leptin receptors

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18
Q

During starvation, ⬇️ [leptin]

What does this cause?

A

hypothalamus produces neuropeptide Y ➡️ transported to PVN (in brain) ➡️:

1) ⬆️ appetite
2) ⬇️ energy expenditure
3) ⬇️ temp
4) ⬇️ reproductive function
5) ⬆️ parasympathetic activity

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19
Q

When ⬆️ [leptin], what does this cause?

A

MSH (melanocyte stimulating hormone) binds to MC4-R ➡️:

1) ⬇️ appetite
2) ⬆️ energy expenditure
3) ⬆️ sympathetic activity

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20
Q

What are the appetite decreasing (satiating) mediators?

A
PYY
CCK
Oxyntomodulin
Insulin
Leptin
CNS mediators (serotonin, dopamine)
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21
Q

What are the appetite stimulating (orexigenic) mediators?

A
Ghrelin
⬇️ leptin
CNS mediators (galanin, opioids)
Glucocorticoids
Norepinephrine
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22
Q

BMI range for overweight? Obese?

A

Overweight: 25-29.9

Obese: greater than or equal to 30

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23
Q

Obesity is a risk factor for development of what conditions?

A

Diabetes mellitus
Hypertension
Heart disease

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24
Q

What are short term regulators of hunger & satiety?

A

Plasma levels of glucose & a.a.

CCK & other hormones

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25
Q

What is ghrelin?

Where is secreted from?

A

Only known appetite stimulating hormone

Stomach

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26
Q

What condition can congenital human leptin deficiency cause?

A

Early onset obesity (defective leptin receptor gene)

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27
Q

What is Prader-Willi syndrome?

What causes it?

A

Most prevalent form of dysmorphic genetic obesity

Absence of paternally derived PWS/AS region of chromosome 15

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28
Q

Angelman syndrome (similar to Prader-Willi): what causes it?

A

Inherited chromosome 15 deletions from mother

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29
Q

What drugs can be used to treat obesity? (Appetite suppression)

A

Sibutramine

Orlistat

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30
Q

At rest, what energy sources does smooth muscle use to maintain cellular integrity?

A

FA catabolism

BCAAs

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31
Q

What is the energy source during exercise generating max power?

A

ATP & Phosphocreatine ➡️ glycolysis from glycogen

32
Q

What is the energy source during high intensity endurance exercise?

A

Phosphocreatine ➡️ glycogenolysis (muscle & liver) ➡️ ⬆️ aerobic oxidation, FA & plasma glucose utilization, BCAA oxidation

33
Q

What is the energy source during low level non-fatiguing exercise?

A

Aerobic oxidation of FAs, glucose, BCAAs

No depletion of phosphocreatine & minimal muscle glycogen used

34
Q

What is metabolic homeostasis? What regulates it?

A

Tendency for biological systems to maintain constant chemical conditions in their internal environments

Endocrine system

35
Q

How are major fuels (CHO, lipid, pro) used to maintain energy requirements?

A

1) maintain blood glucose level w/in normal limits
2) maintain optimal glycogen supply
3) maintain optimal pro supply

36
Q

How is body weight regulated?

A

1) food intake
2) heat loss
3) energy expenditure (e.g. exercise)

37
Q

General description of the heart & its energy use/requirements?

A

Scavenger: uses anything for energy (FAs, glucose, KBs)

38
Q

General description of the brain & its energy use/requirements?

A

Selfish: uses majority of glucose, also uses KBs in starvation

39
Q

General description of the liver & its energy use/requirements?

A

Unselfish: provider of nutrients to other tissues, “mother figure”

Uses fat (not glucose) for energy

40
Q

Main metabolic roles of liver?

A

1) 1st to receive nutrients from intestines (EXCEPT fats)
2) Deliver bile to intestines (cholesterol homeostasis)
3) Main site of glycogen deposition & blood glucose maintenance
4) important in lipid, protein, & nitrogen homeostasis
5) supplies energy via FA oxidation

41
Q

Difference between brown adipose & white adipose?

A

Brown adipose: produce heat; contain lots of mitochondria

White adipose: export triacylglycerol as FAs

42
Q

Main metabolic roles of skeletal muscle?

A

1) contains most of body’s nonlipid fuel
2) has 4x more glycogen than liver (but less concentrated)
3) lacks G6P ➡️ can’t be a source of blood glucose
4) starvation: provides a.a. (main carbon source for glucose homeostasis)
5) Part of Cori cycle

43
Q

Main metabolic roles of kidneys?

A

1) a.a. homeostasis

2) gluconeogenesis (fasting)

44
Q

Main metabolic roles of blood/body fluids?

A

1) contains simple CHOs, a.a. (⬆️ ala, gln), anions, TCA intermediates, toxic metabolites, macromolecules
2) has albumin: transports FAs, drugs, toxic metabolites, indicator of liver function, osmotic regulator
3) has lipoproteins

45
Q

What hormones does the endocrine pancreas secrete? What cell types secrete each hormone?

A
Secretes:
insulin (beta cells)
glucagon (alpha cells) 
somatostatin (delta cells)
pancreatic polypeptide (F cells)
46
Q

Structure of insulin?

Steps of insulin biosynthesis?

A

A & B chain + C peptide

preproinsulin ➡️ proinsulin ➡️ packaged into secretory granules ➡️ conversion to insulin + C peptide

47
Q

What is lispro insulin?

How is it structurally different from other insulin?

A

Artificial, no dimer formation, insulin used to treat diabetes

28Pro29Lys on B chain are switched

48
Q

How can you measure how much insulin the body is making?

A

Measure C peptide

49
Q

What things ➕ insulin secretion?

A

Glucose, a.a., glucagon-like peptide, acetylcholine, beta-adrenergic agents, sulfonylurea

50
Q

What things ➖ insulin secretion?

A

Somatostatin, alpha-adrenergic agents, diazoxides

51
Q

What are the biological actions of insulin?

A

1) ➕ fuel storage & protein synthesis (➖ breakdown)

2) ➕ glucose uptake into muscle & adipose via GLUT4

52
Q

Describe the structure & function of the insulin receptor.

A

Heterotetramer (2 alpha, 2 beta subunits)

tyrosine kinase (insulin binds to extracellular alpha subunits ➡️ intracellular domain of beta subunits self-phosphorylate)

53
Q

What conditions involve problems with the insulin receptor?

A

Leprechaunism/Donohue syndrome: ⬇️ functionality of insulin receptor

Type A insulin resistance (autoimmune disease, mutation in insulin receptor genes)

54
Q

What are the short acting insulins?

A

Lispro
Aspart
Glulisine

55
Q

What are the long-acting insulins?

A

Glargine

Detemir

56
Q

Steps of insulin secretion?

A

Glucose enters beta cells (via GLUT1 and 2) ➡️ convert to G6P (via glucokinase) ➡️ ATP production ➡️ ➖ ATP-sensitive K+ channel ➡️ ⬇️ K+ efflux ➡️ membrane depolarization ➡️ Ca2+ influx ➡️ insulin release from granules

57
Q

How do sulfonylurea and diazoxides affect insulin secretion?

A

Sulfonylurea: inhibits K+ channel via sulfonylurea receptors (SUR) ➡️ ➕ insulin secretion

Diazoxides: keeps K+ channels open via SUR ➡️ ➖ insulin secretion

58
Q

How does somatostatin affect insulin secretion?

A

➖ Ca2+ influx ➡️ ➖ insulin secretion

59
Q

How does acetylcholine affect insulin secretion?

A

➕ Gq protein ➡️ ➕ phospholipase C-IP3-Ca2+ ➡️ ⬆️ insulin secretion

60
Q

How does epi & norepi affect insulin secretion?

A

Bind to alpha-adrenergic receptor sites ➡️ ➕ Gi protein ➡️ ➖ adenylate cyclase ➡️ ⬇️ cAMP ➡️ ⬇️ protein kinase A activity ➡️ ⬇️ insulin secretion

61
Q

How does glucagon-like peptide 1 (incretin) affect insulin secretion?

A

➕ Gs protein ➡️ ➕ adenylate cyclase ➡️ ⬆️ cAMP ➡️ ⬆️ protein kinase A activity ➡️ ➕ insulin secretion

62
Q

What does glucagon stimulate?

A

⬆️ in blood glucose:

➕ glycogenolysis, gluconeogenesis, ketogenesis in liver
➕ lipolysis of TG in adipocytes

63
Q

What enzymes ➕ with ⬆️ insulin/glucagon ratio?

A

Glucokinase, citrate cleavage enzyme, acetyl-CoA carboxylase, HMG-CoA reductase, pyruvate kinase, PFK1, PFK2, F-2,6-BPase ➡️ glycolysis

64
Q

What enzymes ➕ with ⬇️ insulin/glucagon ratio?

A

G6Pase, PEP carboxylase, F-1,6-BPase ➡️ gluconeogenesis

65
Q

Under what circumstances is glucagon secreted?

Under what circumstance is glucagon secretion inhibited?

A

Secreted: hypoglycemia, ⬇️ blood glucose, ⬆️ blood a.a., exercise

Inhibited: ⬆️ blood glucose

66
Q

What does somatostatin do in the pancreatic islets? Pituitary gland? Gut?

A

Islets: ➖ insulin & glucagon secretion
Pituitary gland: ➖ GH & TSH release
Gut:➖ gastrin & motilin secretion

67
Q

When is pancreatic polypeptide secreted? What is its potential effect on pancreas?

A

Secreted in response to fuel ingestion

May affect pancreatic exocrine secretion of HCO3- and proteolytic zymogens

68
Q

What are the 2 principal energy stores?

A

Triacylglycerol & proteins

69
Q

CHO digestion & absorption: compare glucose, galactose, & fructose?

A

Glucose & galactose ➡️ direct into blood via enterocytes (Na+ dependent co-transport)

Fructose: absorbed by specific system (GLUT V) ➡️ some metabolized in enterocytes, rest enters portal blood to be used by liver & kidneys

70
Q

Glucose tolerance (in fasting state): consume 75g glucose and monitor blood glucose over time

What are the values for normal & diabetes?

A

Normal: < 110 mg/dL

Diabetes: > or equal to 200 mg/dL

71
Q

How do catecholamines trigger utilization of hepatic glycogen?

A

Catecholamines released w/⬆️ stress & high intensity exercise ➡️ ➕ Ca2+ release from ER & ➕ phosphorylase kinase ➡️ ➕ glycogen phosphorylase ➡️ glycogenolysis

72
Q

What enzyme is the key step in regulation of glycolysis in skeletal muscle?

What inhibits this enzyme? What activates it?

A

PFK

➖: ATP
➕: Pi, 5’-AMP, ADP

73
Q

What allosterically regulates skeletal muscle phosphorylase?

A

5’-AMP

74
Q

What are the 3 sources used as substrates for gluconeogenesis?

A

Glycerol
Lactate
Glucogenic a.a.

75
Q

What things regulate gluconeogenesis?

A

➕, acute: Glucagon & epinephrine

➕, chronic: glucocorticoid (cortisol)

➖: absence of insulin