Final Review Flashcards
How does insulin activate glycogen synthase?
By inactivating GSK3 & activating PP1
Glucagon stimulates _________ and _________ while blocking glycolysis
glycogen breakdown and gluconeogenesis
What does it mean to say the membrane lipid bilayer is amphipathic
it contains both hydrophilic and hydrophobic regions
What metabolite links glycolysis and CAC?
pyruvate
Epinephrine causes an _______ of blood glucose levels while insulin causes an ________ of BGL
epinephrine causes an increase of BGL and insulin causes a decrease
main composition of lipid bilayer
phospholipids & sphingolipids
which leaflet of the membrane is more positively charged
outer leaflet
what enzymes catalyze trans bilayer flip flop diffusion of lipids
lipid translocators (flippases, floppases, scramblaes)
Lipid raft composition
glycosphingolipids and cholesterol
How is the membrane able to undergo fusion with other membranes w/out losing continuity?
changes in curvature
* curvature is required for cell fusion
GPCRs are active when
GTP bound
2nd messengers
cAMP, diacylglycerol, IP3 or Ca2+
- either inhibit or activate one or more downstream targets usually protein kinases
What does it mean that stimulation of adenylyl cyclase is self-limiting
Gs alpha has intrinsic GTPase activity that switches Gs alpha into its inactive form by converting the bound GTP for GDP
** stimulated by GTPase activator protein
3 ways to terminate the Beta Adrenergic System
- desensitization - [epinephrine] in blood drops below the Kd for its receptor
- Hydrolysis of GTP–>GDP via intrinsic GTPase activity
- removing cAMP
_____ Hormone made in the adrenal glands that mediates the body’s stress response by mobilizing E in the form of glucose
– causes an increase in blood glucose levels
epinephrine
_____ causes a decrease in blood glucose levels
insulin
How does cAMP activate PKA
cAMP binds at the two R subunits causing them to undergo a conformational change that moves the autoinhibitory domain out of the catalytic domain causing the two R2C2 complex to dissociate and yield two catalytically active C subunits
PLC cleaves PIP2 into what two things
Diacylglycerol and IP3
IP3 causes the release of Ca2+ and together with Diacylglycerol, Ca2+ and DAG activate pKC
What molecules regulate the desensitization of the epinephrine pathway
BARK and Beta Arrestin
PKA is localized to particular structures by its anchoring/adaptor protein _____
AKAP5
Why are the inside of cells negatively charged
due to the asymmetric transport of cations by the NA+K+ATPase (3 Na+ go out as 2K+ come in)
what regulates the timing of the cell cycle
cyclin-dependent kinases
What are the first two steps of gluconeogenesis
- pyruvate converted to oxaloacetate via pyruvate carboxylase
- oxaloacetatee converted to PEP (phosphoenolpyruvate) via PEP carboxylase
Purpose of gluconeogenesis
allows for the generation of glucose when glycogen stores have been depleted (starvation/excercise)
Why does oxaloacetate need tot be converted into PEP or malate during gluconeogenesis?
b/c oxaloacetate cannot escape the inner mitochondrial membrane but malate,PEP and pyruvate can
Hexokinase I,II,III are all regulated by?
Glucose-6-phosphate
Hexokinase IV is regulated (inhibited) by
Fructose-6-phosphate
What enzyme catalyzes the conversion of F-6-P to F-1,6-BP
PFK-1
What increases PFK-1 activity (thus promoting glycolysis)
AMP & ADP
What inhibits PFK-1, inhibiting glycolysis
ATP, citrate
What converts PEP to pyruvate
pyruvate kinase +ADP and Pi
Why is pyruvate converted into PEP
when fatty acids are available and when acetyl-coA signals that no more E production is needed
products of the pentose phosphate pathway
NADPH & Ribose-5-phosphate which are necessary for producing fatty acids, cholesterol and sterols
what inhibits pentose phosphate pathway
NADPH
Transaminations - what is the cofactor and what is the enzyme
catalyzed by aminotransferases & PLP (pyridoxal phosphate) is the cofactor
What is a transamination reaction
transfer of an alpha amino group from an alpha amino acid to an alpha-keto acid
What is a transamination reaction?
transfer of an alpha amino group from an alpha amino acid to an alpha-keto acid
What is the purpose of step 2 in glycolysis?
makes the next steps in the reaction require less energy –C1 of fructose is easier to phosphorylate by PFK , allows for symmetrical cleavage by aldolase
What is the purpose of step 3 in glycolysis?
the 2nd phosphorylation converts fructose-6-phosphate to fructose-1,6-bisphosphate
– this is the first committed step of glycolysis…b/c fructose 1,6 bisphosphate is committed to becoming pyruvate
What is the purpose of step 4 in glycolysis?
Step 4 is the aldol cleavage of a 6-carbon sugar into two 3-carbon sugars GAP and DAP
What is the purpose of step 5 in glycolysis?
This step completes the preparatory phase of glycolysis - allows glycolysis to proceed to the payoff phase by a single chemical pathway
conversion of dihydroxyacetone phosphate to GAP (glyceraldehyde-3-phosphate)
What is the purpose of step 6 in glycolysis?
– incorporates inorganic phosphate
– the first energy-yielding step in glycolysis, produced NADH
Pathway that converts pyruvate (and its related 3 and 4 carbon compounds) to glucose
gluconeogenesis
What molecules in gluconeogenesis are permeable to the mitochondrial membrane…which are impermeable
Permeable molecules = Malate, PEP, pyruvate
IMpermeable = oxaloacetate
What is oxaloacetate converted to in order to allow for transport to the cytosol for gluconeogenesis?
oxaloacetate can be converted to PEP or malate
A reason why gluconeogenesis is physiologically necessary
The brain, NS, and red blood cells can only generate ATP from glucose
In mammals, where is the main site of gluconeogenesis
liver
How is phosphofructokinase-1 (PFK-1) regulated?
PFK-1 is regulated by the binding of ATP to an allosteric site - this occurs when there is an excess in ATP
Citrate inhibits PFK-1 by increasing the inhibitory effects of ATP – causes a smaller concentration of ATP to seem like more
How is (FBPase) fructose 1,6 bisphosphate ALLOSTERICALY regulated (inhibited)
high concentrations of AMP (low ATP) inhibit FBPase –> thus slowing glucose synthesis
high ATP concentrations slow glycolysis and speed up gluconeogenesis
How does F26BP regulate PFK-1
Binds to PFK-1 and increases its affinity for fructose-6-phosphate
Hows does F26BP regulate FPBase-1?
binds to FPBase-1 and REDUCES its affinity for substrate
Under aerobic conditions what does pyruvate become?
pyruvate gets oxidized to acetyl-coA
High ______ concentrations inhibit the committed step of glycolysis to prevent excess glucose degradation
ATP
3 things that affect the rates of biochemical reactions
- Concentration of reactants
Rate = k[reactants] - activity of the catalyst
the concentration of the enzyme & intrinsic activity of the enzyme - Concentration of effectors
What is the breakdown of cellular glycogen to glucose-1-phosphate ?
glycogenolysis
What enzyme performs the isomerization of glucose 1-phosphate to glucose-6-phosphate
Phosphaglucomutase
What substrate serves as the primer for glycogen synthesis
glycogenin
What stimulates the conversion of phosphorylase b (inactive) into a (active)?
breaking down glycogen = cells need more E
* epinephrine (muscle activity)
* glucagon in liver
What molecule converts glycogen synthase a (active) to synthase b (inactive) by adding phosphoryl groups to three serine residues on synthase a
Inactive glycogen synthase = stop using glucose to make glycogen
GSK3: Glycogen synthase kinase 3
What inactivates GSK3 (which itself inactivates glycogen synthase)
insulin bc inslun says hey we have exttra glucose time to sttorage that bitch
What must happen before glycogen synthase kinase 3 (GSK3) can phosphorylate glycogen synthase?
Casein Kinase II (CKII) must first phosphorylate the glycogen synthase on a nearby residue
Glycogen breakdown is catalyzed by?
glycogen phosphorylase
