Section IV Part 1 (Chapters 19-20, 22-23) Flashcards
What is metabolic homeostasis?
The control of the supply and demand of carb, fat or protein, from which ATP is derived
How is homeostasis regulated?
Concentration of metabolites in blood (too much = Store it; too little = Use/Breakdown)
Hormonal control - (Insulin vs Glucagon/Epinephrine/Cortisol)
CNS direct tissue metabolism directly or via hormones
How does insulin maintain homeostasis & regulate fuel mobilization & storage?
Anabolic hormone that promotes storage & growth when blood glucose is high
Made by beta cells of the pancreas
How does glucagon maintain homeostasis & regulate fuel mobilization & storage?
A counterregulatory hormone of insulin
Fuel mobilization hormone
Promotes release/use/breakdown of fuel stores during fasting/stressful states
Through the liver (glycogenolysis/gluconeogenesis) & adipose tissue (fatty acid release)
Made by alpha cells of the pancreas
How does epinephrine & cortisol work in terms of fuel mobilization
From the CNS, epinephrine & cortisol are insulin counterregulatory hormones, released due to stress/exercise/hypoglycemia
Increase the availability of fuel
Insulin stimulates
-> Glucose storage as glycogen
-> Stimulates fatty acid synthesis & storage
-> Stimulates amino acid uptake & protein synthesis
Glucagon activates
Gluconeogenesis & glycogenesis
Fatty acid release from adipose tissue
Epinephrine stimulates…
Stimulates glucose production from glycogen (muscle & liver)
Stimulates fatty acid release from adipose
Cortisol stimulates…
Stimulates amino acid mobilization from muscle protein
Stimulates gluconeogenesis in order to produce glucose for liver glycogen synthesis
Stimulates fatty acid release from adipose tissue
How is insulin produced?
A peptide hormone synthesized by BETA-cells from the iL of the pancreas; initially a preprohormone, converted to proinsulin in rough ER (via cleaved N-terminal) and folded with cystine disulfide bonds, then transported to Golgi to become active insulin that coprecipitates with Zn in vesicles
Why is C-peptide clinically significant?
Proteases remove the C-peptide, which decreases the solubility
How is glucagon produced?
A peptide hormone made by ALPHA-cells of iL of the pancreas; First, preproglucagon, converted to proglucagon in RER and later cleaved to mature glucagon
What is the physiological mechanism of insulin secretion by the pancreatic islets cells?
Abundant glucose enter BETA-cell via GLUT2 and is oxidized to g6p then into glycolysis, TCA, and oxidative phosphorylation creating ATP; the rise in ATP in BETA-cell closes K+ channels (= depolarize PM) and activates Ca2+ channels, leading to Ca2+ influx and vesicular release of INSULIN
What are the regulators of insulin?
Major -> glucose
Minor -> amino acids, neural input, gut hormones, epinephrine (adrenergic)
What are the regulators of glucagon?
Major -> glucose, insulin, amino acids
Minor -> cortisol, neural, epinephrine
What regulator of insulin gives a negative effect (only one)?
Epinephrine
What regulator of glucagon gives a negative effect (only two)?
Glucose & insulin
Cell signaling of insulin
Insulin bind to plasma membrane receptor with tyrosine kinase activity = phosphorylation of enzymes = IRS binds to proteins = different tissue-response: reverse glucagon effect, more phosphorylation cascade; growth/ protein synthesis; induce/repress enzymes; AND glucose/AA transport into cells
Cell signaling of glucagon
Glucagon bind G-protein receptor which is coupled to adenylate cyclase = cAMP production = activate PKA = phosphorylation of S-residues: glycogen degradation, inhibit glycogen synthesis and glycolysis in liver, kidney, but NOT skeletal muscle (lack glucagon receptor)
Cell signaling of epinephrine
EPI is similar to glucagon, though bind to adrenergic receptors = activate G protein = cAMP production & PKA or PIP2 system; WILL affect skeletal muscle
Cell signaling of cortisol
Cortisol is a steroid hormone = traverse plasma membrane; bind intracellular receptors; form complex; enters nucleus and directly interact with DNA to alter gene transcription: induce gluconeogenesis to blood glucose levels
Molecular pathology of maturity-onset diabetes of the young (MODY)
Mutated pancreatic glucokinase (ATP); dampen insulin release, need to be at higher blood glucose concentration for insulin to be released at baseline
Type I diabetes mellitus pathology
Autoimmune attack of BETA-cells = no insulin production = treated by insulin injections
Type II diabetes mellitus pathology
Insulin resistance via non-responsive receptors (receptor number and affinity are still normal) = treated by diet changes and watching sugar intake
Insulinoma pathology
BETA-cell tumor that hypersecretes insulin = causes low blood glucose
Neonatal diabetes
One cause of neonatal diabetes is a mutation in a subunit of the K+ channel in various tissues. Such a mutation in the pancreas leads to permanent opening of the K+ channel, keeping intracellular Ca2+ levels lows, and difficulty in releasing insulin from the beta-cells
What is delta G?
Defined as the quantity of free energy that can be used to work; energy level between product and substrate of a rxn; depends on temperature, pH and pressure
Negative delta G means…
Exergonic/spontaneous
Positive delta G means…
Endergonic/nonspontaneous
Delta G energy production must be … than delta G energy use in order for cells to …
Higher, live
What is the role of ATP as an energy currency?
ATP is the energy currency of life
What is the operation of the ATP/ADP cycle?
Oxidation produces ATP that can be hydrolyzed to ADP and provide energy to perform work
Hydrolysis of ATP to ADP releases energy because ADP and phosphate are more stable with lower bond energy
Usually regulated by phosphoryl transfer reactions, not directly hydrolysis
What is the structure/property/function of ATP
Phosphoanhydride bonds/unstable bonds between the phosphate groups of ATP (due to repelling negative charges) can be hydrolyzed to form more stable substrates (ADP and inorganic phosphate); this is a favorable rxn that releases energy as heat
What does a high-energy bond mean?
Any bond that releases as much energy as the ATP
What are the high energy bonds in molecules other than ATP?
UTP (combine sugars), GTP (proteins) and CTP (lipid) are equal to ATP in energy
What is mechanical work?
the conversion of chemical bond energy to physical movement via conformation change of protein, an example is muscle contraction; ATP hydrolysis while bound to myosin ATPase changes the conformation of myosin
What is biochemical work?
Transfers energy from the cleavage of ATP to power the rxns that require energy such as anabolic/biosynthetic pathways; DNA synthesis, glycogen synthesis, ammonia conversion to urea)
What is the daily ATP consumption of the heart?
16
What is the daily ATP consumption of the brain?
6
What is the daily ATP consumption of the kidneys?
24
What is the daily ATP consumption of the liver?
6
What is the daily ATP consumption of the skeletal muscle at rest?
.3
What is the daily ATP consumption of the skeletal muscle (while running)?
23.6
What is greater than muscle when exercising in terms of ATP consumption?
Kidneys
What is reduction potential?
Energy change when a compound accepts an electron (e-) or becomes reduced; the more negative the potential = greater energy for ATP generation available when e- is passed on to oxygen