Metabolic regulation Flashcards
glucose and intracellular ATP maintaine at ___mM to maintain homeostasis
5
Hexokinase is an ____which catalyze the same reaction although they have slightly different properties. Made from different genes with diff regulatory aspects.
isoenzyme
ATP, ADP and AMP bind to ___enzymes and change their activity level. They are examples of ____modifiers
regulatory; allosteric
Covalent modification is
phosphorolation
What is a futile pathway
ATP is hydrolyzed and nothing is gained when glycolyis and gluconeogenis is happening at the same time. So they are reciprocally regulated
Glucose gets into cell via ___
GLUT 4
GLUT 4 is ___dependent
insulin; otherwise sequestered internally in vesicles
What are 3 points of regulation for glycolysis
- Hexokinase
- Phosphofructokinase 1
- Pyruvate kinase
What are 3 points of regulation for gluconeogenesis
- Glucose 6-phosphatase
- Fructose-1, 6-bisphosphatase
- Pyruvate carboxylase + PEP carboxykinase
Glucokinase is liver specific____
isozyme; will forgoe glucose to make sure brain has enough.
Hexokinase 4 is sequestered in ____when glucose concentration is low.
nucleus. Cant encounter glucose and phosphorolate it so its kept in cell.
When glucose levels are ____ it binds to hexokinase 4 and releases it from the nucleus so it can start phosphorolating glucose so that it can be stored as glycogen
high
PFK 1 in glycolysis is an ____regulator
allosteric
High [ATP] and [citrate] allosterically signal that energy needs are met and inhibit:
PFK-1
High [ADP] and [AMP] allosterically signal need for ATP production and activate ____ and inhibit ___
PFK-1; FBPase-1
In the liver, the most important allosteric regulator of PFK-1 is _____ which is synthesized by _____
fructose, 2-6 bisphosphate; PFK-2
Glycogen stores in muscle can’t help maintain blood glucose levels bc it is never:
released. Doesn’t have glucose 6 phosphatase. Only uses glycogen for itself
Muscles have _____ receptors but no ____receptors; therefore it does not produce the enzymes for gluconeogenesis.
epinephrine; glucagon
What are the 3 principle hormones of fuel metabolixm
- insulin: fed
- glucagon: hungry
- epinephrine: terrified
Where does epinephrine come form
adrenal medulla; its actually a catacholamine
What is a phenol ring with two hydroxyl groups called
catecolamine. Derived directly from aa - tyrosine; have cell membrane associated receptors and trigger a second messenger
What is the classical second messenger
cyclic AMP
Where does glucagon come from
alpha cells of pancreas–>islets of Langerhaans
Pancreas has ___ and ___ functions
exocrine: digestive enzymes
endocrine: releases proteins into bloodstream so it can go throughout the body
Beta cells make
insulin
Glucagon is a ____hormone
protein
What are the targets of glucagon and epinephrine
Use cyclic amp signaling to change metabolic activity.
What is a serpentine receptor
External ligand binding to receptor activates an intracellular GTP binding protein which regulates an enzyme that generates an intracellular second messenger. Go back and forth across cell membrane and when hormone binds it activates G protein
What are the 5 proteins involved in epinephrine and glucagon signaling
- beta adrenergic receptor/glucagon receptor
- Gs protein
- adenylate cyclase
- protein kinase A
- cyclic nucletodie phosphodiesterase
- Epeniphrine binds its specific receptor –>changes conformation of receptor site and G protein. When receptor binds it knocks off ___ and GTP associates. Alpha subunit loses affinity for its receptor and moves into cell membrane and binds to target enzyme: ______GDP falls off and GTP binds. Now has high affinity for target enzyme.
GDP; adenylate cyclase
What is adenylate cyclase
the enzyme that converts ATP to cyclic AMP
Protein Kinase A becomes activated by ____and changes metabolic activity of all of its protein targets by:
cyclic AMP; phosphorlation
What are ways to self limit this process?
- G protein has inherent GTPase function: hydrolyze GTP, converts it to GDP which now has affinity for the receptor and its beta and gamma subunits. Moves back into its original position.
- cAMP doesnt hang around all day. Cyclic nucleotide phosphodiesterase hydrolizes cAMP and inactivates it
cAMP phosphodiesterase is inhibited by:
caffeine and theophylline
How is protein Kinase A activated; what does it catalyze
cAMP; catalyzes the phosphorylation of target proteins
Insulin DOES NOT produce ____as a secondary messenger
cAMP
What are C peptides indicative of
diagnostic tool that tells you if your body makes natural insulin and differentiates between Type 1 and Type 2 diabetes
Which aa form disulfide bonds?
cysteine
Insulin receptors come from:
receptor tyrosine kinases
“RTK”; cell signaling proliferation and growth
3 aa that have hydroxyl groups:
- serine
- threonine
- tyrosine
What do insulin receptors do
Auto phosphoralates its own tyrosine receptors that activates receptor and other targets.
How does insulin signaling I occur
- Insulin binds to receptor and autophosphorolates on its own tyrosine residues
2.
Growth factors cause
cell proliferation
Insulin is a potent ___factor that activates the ____pathway
growth; MAPK –> regulate transcription factors needed for cell division
What is Ras
G protein; when GDP bound its inactive when GTP bound it activates Raf 1 Kinase that starts MAPK cascade that turns on genes for cell division.
Ras is commonly _____in different cancers.
mutated. –>in GTPase domain; the part that is meant to turn off the singal. Cell keeps dividing
IRS 1 can interact with
multiple targets.
How does insulin signaling II occur
PKB activated by IRS1, which leads to phosphoprotein phosophatase 1 which takes phosophate group off that protein kinase A phosphorolates.
What is the major modulator for PFK-1
Fructose 2,6 bisphosphate; allosterically increases PFK-1 affinity for F-6-P (fructose 6 phosphate); decreases PFK-1 affinity for ATP and citrate
PFK-1 activation favors
glycolysis
Active PFK-2, means there is a high amount of Fructose, 2-6 BP which activates ____ and favors___
PFK1; glycolysis
If PFK-2 gets phosphorolated it becomes ___
inactivated; glycolysis would stop and gluconeogenesis would happen
PFK-2 is a ____enzyme
bifunctional; also takes phosphate back off.
What does pyruvate kinase do in glycolysis
Converts PEP to pyruvate and makes ATP; this is the first step thats irreversible in gluconeogenesis
If ATP levels are high glycolysis:
slows down
if ADP and AMP are high
we will need to make more ATP
Liver has special isoenzyme of pyruvate kinase that is inactivated by_____. When blood glucose falls, ______is secreted. _____ levels increase. ____is activated. PFK-2 is phosphorolated and inactivated. _______ decreases; _____ activity decreases. Glycolysis slows down. Pyruvate kinase is _____ and inactivated.
PKA phosphorolation; glucagon; cAMP; PKA is activated; Fructose 2, 6 BP; PFK-1; phosphorolated.
Gluconeogenesis is favored in the
liver
pyruvate carboxylase is activated by
acetyl coA
High levels of insulin blocks the transcription of
PEPCK; thus reducing gluconeogenesis.
