Fed and Fasted State Metabolism Flashcards
____ availability and the needs of ____are balanced in the body by level of nutrients hormone levels and nerve impulse
Fuel
Tissue
The ____ state is immediately after a meal, and last 2 to 4 hours. After that the body switches to a ____ State. If there’s no further nutrition, there is a transition to the ____ state, which can persist for weeks.
Fed
Fasted
Starved
Dietary fuels are transported from the ___ of the gut to the ___ in digestion. Excess fuels are stored as ____, fat, and protein.
Lumen
Blood
Glycogen
_____ promotes storage pathways. These stored fuels are made available for later use by ___, cortisol and catecholamines.
Insulin
Glucagon
If glucose concentration is high in the blood _____ is released from pancreatic beta cells. This represses ___ release from pancreatic alpha cells.
Insulin
Glucagon
In the fasted state ____ is the dominant hormone. ____ ____ catabolism is being performed in this state.
Glucagon
Amino acid
In the Fed state ____ is the dominant hormone. _____ catabolism is being performed.
Insulin
Carbohydrate
In the starved state ____ along with catecholamines and cortisol, are the dominant hormones. ___ ____ catabolism is being performed.
Glucagon
Fatty acid
What is the significance of the ratio of insulin to C-peptide?
Pancreatic beta cells express the ____ gene. It is first translated as a single large protein, which is then processed into 2 chains through removal of the ___ ____. Disulfide bonds link the two peptide chains after the C-peptide is removed.
INS1
C-peptide
Insulin synthesis:
Pancreatic beta cells produce insulin as a large _____. A signal protein directs it to the lumen of the ___ ____ is the first cut off, followed by removal of the C-peptide in the ___. ____ bonds link the two peptide chains. Mature insulin is stored in ___ ____ stabilized by zinc atoms.
Pre-protein
Endoplasmic reticulum
Golgi
Disulfide
hexameric crystals
Blood glucose enters the liver cell through the high Kd ____ transporter, and is oxidized to generate ___. The high level of ATP, then inhibits ____ channels, causing depolarization of the cell. This causes voltage gated ____ channels to open. An influx of ____ causes proteins on insulin containing vesicles to fuse with the ___ ___ and release insulin to the blood.
GLUT2
ATP
K+
Calcium
Calcium
Plasma membrane
The insulin receptor is a ___ ____. When insulin binds, it activates a kinase that phosphorylates ____ on itself and other proteins. This makes more binding sites, and ___ ___ at the membrane.
Tyrosine kinase
Tyrosine
Aggregate proteins
The insulin receptor has two main signaling arms:
Through ___ ____ to PKB and through ____ to MAPK.
Phosphatidylinositol 3-kinase (P13-kinase)
Grb2
PI 3-kinase phosphorylates the membrane phospholipid _____ _____ to form phosphatidylinositol 3,4,5-triphosphate. PI-3,4,5-trisP then recruits ___ and ___. PKB is phosphorylated by ____ and activated. It’s phosphorylates many substrates to promote ____ processes.
Phosphatidylinositol 4,5-biphosphate
PDK1 and PKB
PDK1
Anabolic
Grb2 recruits ___ to the membrane which is a ____ nucleotide exchange factor (GEF), allowing Ras to swap guanosine diphosphate for guanosine triphosphate. This activates ____ which then binds and activates ___. Raf initiates a cascade of phosphorylation’s ultimately activating transcription factors that remodel gene expression to promote ____.
SOS
Guanosine
Ras
Raf
Anabolism
Insulin ____ the uptake of glucose in skeletal muscles and adipocytes and promotes it’s conversion to ____ ___ and ____. While activating a storage pathways, insulin also ____ the corresponding pathways that release stored fuels.
Promotes
Fatty acids
Glycogen
Represses
In the muscle and adipose cells, ____ activation by insulin results in translocation of intracellular vesicles that contain the ____ glucose transporter to the plasma membrane. This increases the rate of glucose uptake in these tissues.
AKT
GLUT4
Insulin promotes the storage of excess carbohydrate as the Glucose polymer ____. The activation of ___ ___ __ (PKB or Akt) and ___ _____ activates glycogen synthesis and inactivates glycogen phosphorylase.
Glycogen
Protein kinase B
Protein phosphatase -1
Protein phosphatase-1 inhibits _____ and activates ____ synthesis.
Glycogenolysis
Glycogen
If nutrition exceeds the immediate work demands, storage pathways are activated:
Glycogen synthesis
Fatty acids synthesis
Cholesterol synthesis
Protein synthesis
When dietary carbohydrates are depleted in the fasted state, the liver supplies ____ to the rest of the body.
_____: generating glucose from stores within the liver.
_____: generating glucose from substrates that come from outside the liver
Glucose
Glycogenolysis
Gluconeogenesis
Low blood glucose is detected by the ____ and the ___.
Hypothalamus
Pancreas
____ is the hungry hormone. It is released into the circulation when there is low glucose, concentration and low levels of insulin. ____, ____, and ____ can also stimulate release.
Glucagon
Cortisol
Epinephrine
Norepinephrine
Glucagon signals through a _____ ___ protein, coupled receptor, which results in mobilization of _____.
Heterotrimeric G
cAMP
Glucagon synthesis:
The hormone glucagon is encoded on the ___ gene. The gene encodes a large pre-protein which is cut into the active hormone ____.
GCG
Glucagon
Glucagon is stored in vesicles within pancreatic ___ ____ cells, until low blood glucose stimulates, it’s released into the blood.
Islet alpha
In high glucose conditions, insulin released by beta cells inhibits glucagon release by ____ alpha cells.
Adjacent
Glucagon has ____ effects in multiple tissues. With respect to carbohydrate metabolism, its most important effect is to increase ____ _____ output.
Pleiotropic
Hepatic glucose
The liver and Adipose are the tissues most affected by glucagon. Glucagon promotes _____ in adipose, and ___ and ____ in the liver, while repressing _____ and fatty acid synthesis.
Lipolysis
Glycogenolysis
Gluconeogenesis
Glycogenogenesis
When glucagon binds the heterotrimeric G protein coupled receptor, the alpha subunit exchanges ____ for ____ and becomes active. The active alpha subunit then activates ___ ___ which produces cAMP
GDP
GTP
Adenyl cyclase
_____ is a second messenger. It’s levels are further regulated by the action of phosphodiesterase.
cAMP
cAMP binds to the regulatory subunits of ___ ___ __, causing them to dissociate from the catalytic subunits, this active protein kinase A then phosphorylates substrates that promote the liberation of ___ ___.
Protein kinase A
Stored fuels
After cAMP causes dissociation of protein kinase A, PKA then phosphorylates ___ ____ that Cleve glucose from glycogen. PKA phosphorylation of ____ _____ reprograms transcription.
Cytoplasmic enzymes
Transcription factors
In the fasted state, hormone sensitive ____ is active and cuts triacylglycerol into ___ ___ and ____.
Lipase
Fatty acids
Glycerol
In the fasted state, hormone sensitive ____ is active and cuts triacylglycerol into ___ ___ and ____.
Lipase
Fatty acids
Glycerol
In the fasted state, hormone sensitive ____ is active and cuts triacylglycerol into ___ ___ and ____.
Lipase
Fatty acids
Glycerol
Fasted state summary:
_____ is a glucocorticoid hormone that is synthesized from cholesterol in the adrenal gland. It is lipid soluble and can diffuse across the plasma membrane. It binds nuclear receptors and activates transcription factors. It increases ______ to increase blood glucose levels.
Cortisol
Gluconeogenesis
_____ is a catecholamine derived from the amino acid tyrosine. _____ is an intermediate in Epinephrine synthesis. ____ circulates in the blood and binds and activates adrenergic receptors. ____ is primarily a signaling molecule for neural synapses.
Epinephrine
Norepinephrine
Epinephrine
Norepinephrine
Mutations in the ___ gene are associated with the development of endocrine tumors, including insulinomas
MEN1
Multiple endocrine neoplasm type one (MEN1) is a syndrome in which patients get multiple tumors in ____ tissue
Endocrine
The MEN1 gene encodes the protein ___. It’s precise function is unclear, but it is known to associate with histone remodeling complexes.
Menin
MLL modulates the histone code at histone three, lysing for the lysine can either be mono di or tri- ____.
Methylated
When menin interacts with the MLL complex, it generates a specific ___ ___ that increases transcription of genes that negatively regulate the cell cycle and ____ tumor development. When menin function is lost due to mutation, this growth, inhibitory function is lost and ___ development is more likely.
Methyl code
Inhibit
Tumor
The steroid hormone receptor family includes the ____ receptor, _____ receptor, and ____ ___ receptor. They function as ligase activated transcription factors. hormones bind the receptors intracellularly. ligand binding displaces ____ ___ proteins (HSP), causing receptor dimerization and translocation to response elements within gene promoters.
Glucocorticoid
Estrogen
Vitamin D
Heat shock
C peptide cleavage helps ___ insulin into the correct form. Our patient has increased C peptide, therefore has ____ insulin levels when she does not need it. Too much ___ insulin. Taking too much glucose out of the blood causing ___.
Fold
Insulin
Active
Hypoglycemia
After C peptide is removed, ____ insulin is two peptide chains held together by ___ bonds
Active
Disulfide
Fed state:
Glucose enters the pancreatic Beta cell via _____ only when blood glucose is high. The beta cell performs ____ to make ATP. ATP also acts as an ___ ___ of potassium channels, causing depolarization. This opens a ____ channel. Calcium then acts as a second messenger to assist insulin containing ____ to fuse with the plasma membrane. The insulin is then released into the ___.
GLUT2
Glycolysis
Allosteric inhibitor
Calcium
Vesicles
Blood
After insulin binds to a tyrosine kinase receptor on a cell, _____ occurs and ATP is phosphorylated
Dimerization
Protein phosphatase-1 ____ the activity of the major pathway activities and phosphorylations of the Fasted state glucagon
Erases
Ras activates Raf, raf activates the ____ pathway which influences gene expression
MAPK
If the muscle is doing work, glucose is converted to ___. If the muscle is not doing work, glucose is converted to ____.
CO2
Glycogen
____ expression occurs rapidly in skeletal muscle cells.
GLUT4
PKB is the same as ____.
Akt
____ is a glucose polymer.
Glycogen
Protein phosphatase-1 (PKB) ___ Glycogenolysis and ____ glycogen synthesis
Inhibits
Activates
____ maintains glucose levels overnight
Glycogenolysis
_____ provides amino acids for gluconeogenesis. ____ provides glycerol for gluconeogenesis.
Proteolysis
Lipolysis
___ ___ converts ADP to cAMP
Adenalyl cyclase
_____ converts cAMP to 5’ AMP, inactivating it
Phosphodiesterase
Fed state
Insulin
80 to 140 mg/dL
Proteolysis
Gluconeogenesis
Disruption in glucose homeostasis hypoglycemia
Overproduction of insulin
_____ is a tumor in the pancreas that secrets insulin unregulated
Insulinoma
