Flashcards in Ch. 20: Perturbations Of Energy Metabolism: Obesity & DM Deck (75):
What is anabolism?
Synthesis of new molecules (requires energy)
What is catabolism?
Breakdown of large molecules ➡️ smaller ones (yields energy)
What is intermediary metabolism?
All changes in a food substance from absorption ➡️ excretion
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
What is basal metabolic rate (BMR)?
Vital energy needs of the body during physical, emotional, and digestive rests
In what situations is BMR ⬆️?
Hyperthyroidism, fever, Cushing's syndrome, adrenal tumors, anemia, leukemia, polycythmia, cardiac insufficiency, injury
In what situations is BMR ⬇️?
Hypothyroidism, starvation, malnutrition, hypopituitarism, hypoadrenalism (Addison's), anorexia nervosa
What is the role of the hypothalamus in mediating feeding behavior?
Integrates signals for energy storage & dissipation
What is the structure of AMP-activated protein kinase (AMPK)?
Heterotrimeric protein complex:
1) Catalytic alpha-subunit
2) Regulatory beta & gamma subunits
How is AMPK activated? Function?
⬆️ [AMP]/ATP ➡️ ➕ AMPK ➡️ ATP synthesis
AMPK also ➕ by: Metformin, Troglitazone, LKB1, CaMKKbeta, other kinases
What are the negative allosteric regulators of AMPK?
What does AMPK activate?
1) p53 ➡️ ⬆️ cell cycle arrest ⬇️ cancer risk
2) TSC2 ➡️ ➖ mTOR ➡️ ⬇️ protein synthesis/cell survival
3) EF2K ➡️ ⬇️ protein synthesis
What does AMPK inhibit?
1) ACC1/FAS ➡️ ⬇️ FA synthesis
2) ACC2 ➡️ ⬆️ FA oxidation
3) HMG-CoA reductase ➡️ ⬇️ sterol synthesis
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
What cells synthesize leptin?
What ⬆️ leptin synthesis? ⬇️ leptin synthesis?
⬆️ leptin synthesis: insulin, glucocorticoids, estrogens
⬇️ leptin synthesis: beta-adrenergic agonists
What does leptin inhibit? What is its function as a regulator?
PPAR-gama2: regulates conversion of preadipocyte to adipocytes ➡️ ⬇️ blood glucose
Why do obese individuals have ⬆️ leptin levels?
Resistance/defect in leptin receptors
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
When ⬆️ [leptin], what does this cause?
MSH (melanocyte stimulating hormone) binds to MC4-R ➡️:
1) ⬇️ appetite
2) ⬆️ energy expenditure
3) ⬆️ sympathetic activity
What are the appetite decreasing (satiating) mediators?
CNS mediators (serotonin, dopamine)
What are the appetite stimulating (orexigenic) mediators?
CNS mediators (galanin, opioids)
BMI range for overweight? Obese?
Obese: greater than or equal to 30
Obesity is a risk factor for development of what conditions?
What are short term regulators of hunger & satiety?
Plasma levels of glucose & a.a.
CCK & other hormones
What is ghrelin?
Where is secreted from?
Only known appetite stimulating hormone
What condition can congenital human leptin deficiency cause?
Early onset obesity (defective leptin receptor gene)
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
Angelman syndrome (similar to Prader-Willi): what causes it?
Inherited chromosome 15 deletions from mother
What drugs can be used to treat obesity? (Appetite suppression)
At rest, what energy sources does smooth muscle use to maintain cellular integrity?
What is the energy source during exercise generating max power?
ATP & Phosphocreatine ➡️ glycolysis from glycogen
What is the energy source during high intensity endurance exercise?
Phosphocreatine ➡️ glycogenolysis (muscle & liver) ➡️ ⬆️ aerobic oxidation, FA & plasma glucose utilization, BCAA oxidation
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
What is metabolic homeostasis? What regulates it?
Tendency for biological systems to maintain constant chemical conditions in their internal environments
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
How is body weight regulated?
1) food intake
2) heat loss
3) energy expenditure (e.g. exercise)
General description of the heart & its energy use/requirements?
Scavenger: uses anything for energy (FAs, glucose, KBs)
General description of the brain & its energy use/requirements?
Selfish: uses majority of glucose, also uses KBs in starvation
General description of the liver & its energy use/requirements?
Unselfish: provider of nutrients to other tissues, "mother figure"
Uses fat (not glucose) for energy
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
Difference between brown adipose & white adipose?
Brown adipose: produce heat; contain lots of mitochondria
White adipose: export triacylglycerol as FAs
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
Main metabolic roles of kidneys?
1) a.a. homeostasis
2) gluconeogenesis (fasting)
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
What hormones does the endocrine pancreas secrete? What cell types secrete each hormone?
insulin (beta cells)
glucagon (alpha cells)
somatostatin (delta cells)
pancreatic polypeptide (F cells)
Structure of insulin?
Steps of insulin biosynthesis?
A & B chain + C peptide
preproinsulin ➡️ proinsulin ➡️ packaged into secretory granules ➡️ conversion to insulin + C peptide
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
How can you measure how much insulin the body is making?
Measure C peptide
What things ➕ insulin secretion?
Glucose, a.a., glucagon-like peptide, acetylcholine, beta-adrenergic agents, sulfonylurea
What things ➖ insulin secretion?
Somatostatin, alpha-adrenergic agents, diazoxides
What are the biological actions of insulin?
1) ➕ fuel storage & protein synthesis (➖ breakdown)
2) ➕ glucose uptake into muscle & adipose via GLUT4
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)
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)
What are the short acting insulins?
What are the long-acting insulins?
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
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
How does somatostatin affect insulin secretion?
➖ Ca2+ influx ➡️ ➖ insulin secretion
How does acetylcholine affect insulin secretion?
➕ Gq protein ➡️ ➕ phospholipase C-IP3-Ca2+ ➡️ ⬆️ insulin secretion
How does epi & norepi affect insulin secretion?
Bind to alpha-adrenergic receptor sites ➡️ ➕ Gi protein ➡️ ➖ adenylate cyclase ➡️ ⬇️ cAMP ➡️ ⬇️ protein kinase A activity ➡️ ⬇️ insulin secretion
How does glucagon-like peptide 1 (incretin) affect insulin secretion?
➕ Gs protein ➡️ ➕ adenylate cyclase ➡️ ⬆️ cAMP ➡️ ⬆️ protein kinase A activity ➡️ ➕ insulin secretion
What does glucagon stimulate?
⬆️ in blood glucose:
➕ glycogenolysis, gluconeogenesis, ketogenesis in liver
➕ lipolysis of TG in adipocytes
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
What enzymes ➕ with ⬇️ insulin/glucagon ratio?
G6Pase, PEP carboxylase, F-1,6-BPase ➡️ gluconeogenesis
Under what circumstances is glucagon secreted?
Under what circumstance is glucagon secretion inhibited?
Secreted: hypoglycemia, ⬇️ blood glucose, ⬆️ blood a.a., exercise
Inhibited: ⬆️ blood glucose
What does somatostatin do in the pancreatic islets? Pituitary gland? Gut?
Islets: ➖ insulin & glucagon secretion
Pituitary gland: ➖ GH & TSH release
Gut:➖ gastrin & motilin secretion
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
What are the 2 principal energy stores?
Triacylglycerol & proteins
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
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
How do catecholamines trigger utilization of hepatic glycogen?
Catecholamines released w/⬆️ stress & high intensity exercise ➡️ ➕ Ca2+ release from ER & ➕ phosphorylase kinase ➡️ ➕ glycogen phosphorylase ➡️ glycogenolysis
What enzyme is the key step in regulation of glycolysis in skeletal muscle?
What inhibits this enzyme? What activates it?
➕: Pi, 5'-AMP, ADP
What allosterically regulates skeletal muscle phosphorylase?
What are the 3 sources used as substrates for gluconeogenesis?