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

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Flashcards in Ch. 20: Perturbations Of Energy Metabolism: Obesity & DM Deck (75):
1

What is anabolism?

Synthesis of new molecules (requires energy)

2

What is catabolism?

Breakdown of large molecules ➡️ smaller ones (yields energy)

3

What is intermediary metabolism?

All changes in a food substance from absorption ➡️ excretion

4

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

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

5

What is basal metabolic rate (BMR)?

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

6

In what situations is BMR ⬆️?

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

7

In what situations is BMR ⬇️?

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

8

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

Integrates signals for energy storage & dissipation

9

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

Heterotrimeric protein complex:
1) Catalytic alpha-subunit
2) Regulatory beta & gamma subunits

10

How is AMPK activated? Function?

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

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

11

What are the negative allosteric regulators of AMPK?

Phosphocreatine
Glycogen

12

What does AMPK activate?

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

13

What does AMPK inhibit?

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

14

What is leptin? Function?

Long term regulator of energy metabolism, hunger & satiety

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

15

What cells synthesize leptin?

What ⬆️ leptin synthesis? ⬇️ leptin synthesis?

Adipocytes

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

16

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

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

17

Why do obese individuals have ⬆️ leptin levels?

Resistance/defect in leptin receptors

18

During starvation, ⬇️ [leptin]

What does this cause?

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

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

19

When ⬆️ [leptin], what does this cause?

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

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

20

What are the appetite decreasing (satiating) mediators?

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

21

What are the appetite stimulating (orexigenic) mediators?

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

22

BMI range for overweight? Obese?

Overweight: 25-29.9

Obese: greater than or equal to 30

23

Obesity is a risk factor for development of what conditions?

Diabetes mellitus
Hypertension
Heart disease

24

What are short term regulators of hunger & satiety?

Plasma levels of glucose & a.a.
CCK & other hormones

25

What is ghrelin?

Where is secreted from?

Only known appetite stimulating hormone

Stomach

26

What condition can congenital human leptin deficiency cause?

Early onset obesity (defective leptin receptor gene)

27

What is Prader-Willi syndrome?

What causes it?

Most prevalent form of dysmorphic genetic obesity

Absence of paternally derived PWS/AS region of chromosome 15

28

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

Inherited chromosome 15 deletions from mother

29

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

Sibutramine
Orlistat

30

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

FA catabolism
BCAAs

31

What is the energy source during exercise generating max power?

ATP & Phosphocreatine ➡️ glycolysis from glycogen

32

What is the energy source during high intensity endurance exercise?

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

33

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

Aerobic oxidation of FAs, glucose, BCAAs

No depletion of phosphocreatine & minimal muscle glycogen used

34

What is metabolic homeostasis? What regulates it?

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

Endocrine system

35

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

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

36

How is body weight regulated?

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

37

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

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

38

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

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

39

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

Unselfish: provider of nutrients to other tissues, "mother figure"

Uses fat (not glucose) for energy

40

Main metabolic roles of liver?

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

Difference between brown adipose & white adipose?

Brown adipose: produce heat; contain lots of mitochondria

White adipose: export triacylglycerol as FAs

42

Main metabolic roles of skeletal muscle?

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

Main metabolic roles of kidneys?

1) a.a. homeostasis
2) gluconeogenesis (fasting)

44

Main metabolic roles of blood/body fluids?

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

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

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

46

Structure of insulin?

Steps of insulin biosynthesis?

A & B chain + C peptide

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

47

What is lispro insulin?

How is it structurally different from other insulin?

Artificial, no dimer formation, insulin used to treat diabetes

28Pro29Lys on B chain are switched

48

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

Measure C peptide

49

What things ➕ insulin secretion?

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

50

What things ➖ insulin secretion?

Somatostatin, alpha-adrenergic agents, diazoxides

51

What are the biological actions of insulin?

1) ➕ fuel storage & protein synthesis (➖ breakdown)
2) ➕ glucose uptake into muscle & adipose via GLUT4

52

Describe the structure & function of the insulin receptor.

Heterotetramer (2 alpha, 2 beta subunits)

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

53

What conditions involve problems with the insulin receptor?

Leprechaunism/Donohue syndrome: ⬇️ functionality of insulin receptor

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

54

What are the short acting insulins?

Lispro
Aspart
Glulisine

55

What are the long-acting insulins?

Glargine
Detemir

56

Steps of insulin secretion?

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

How do sulfonylurea and diazoxides affect insulin secretion?

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

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

58

How does somatostatin affect insulin secretion?

➖ Ca2+ influx ➡️ ➖ insulin secretion

59

How does acetylcholine affect insulin secretion?

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

60

How does epi & norepi affect insulin secretion?

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

61

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

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

62

What does glucagon stimulate?

⬆️ in blood glucose:

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

63

What enzymes ➕ with ⬆️ insulin/glucagon ratio?

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

64

What enzymes ➕ with ⬇️ insulin/glucagon ratio?

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

65

Under what circumstances is glucagon secreted?

Under what circumstance is glucagon secretion inhibited?

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

Inhibited: ⬆️ blood glucose

66

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

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

67

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

Secreted in response to fuel ingestion

May affect pancreatic exocrine secretion of HCO3- and proteolytic zymogens

68

What are the 2 principal energy stores?

Triacylglycerol & proteins

69

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

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

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

What are the values for normal & diabetes?

Normal: < 110 mg/dL

Diabetes: > or equal to 200 mg/dL

71

How do catecholamines trigger utilization of hepatic glycogen?

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

72

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

What inhibits this enzyme? What activates it?

PFK

➖: ATP
➕: Pi, 5'-AMP, ADP

73

What allosterically regulates skeletal muscle phosphorylase?

5'-AMP

74

What are the 3 sources used as substrates for gluconeogenesis?

Glycerol
Lactate
Glucogenic a.a.

75

What things regulate gluconeogenesis?

➕, acute: Glucagon & epinephrine

➕, chronic: glucocorticoid (cortisol)

➖: absence of insulin