Enzymes Subject to Phosphorylation

 

Ca++ and cAMP are intracellular 2nd messengers that respond to hormones binding cell surface receptors

When adenylate cyclase is stimulated, intracellular cAMP levels are elevated (made from ATP)

 

All protein phosphorylation (by kinases) is ATP-dependent and dephosphorylation (by phosphatases) uses H2O and releases Pi

 

 

ENZYME Substrate, action Modifying enzymes

Phosphorylated +P

Dephosp “-P” RESULT
cAMP-dependent protein kinase or PKA Responds to increased CAMP levels…adds P to many enzymes (on Ser, Thr)        
Protein Phosphatase I Hydrolyzes phosphate group off various enzymes inhibitor I     Forms inactive complex with phosphorylated Inhibitor I
Inhibitor I Inhibits protein phosphatase I PKA Active complex, binds to prot. phosphatase Inactive Glucagon and epi stimulate PKA, which inhibits protein phosphatase to slow the -P of glycogen synthase, phosphorylase, and phosphor. kinase
           
Muscle phosphorylase glycogenolysis Phosphorylase kinase (reverse, protein phosphatase I) More active phosphorylase “a” (not subject to allosteric effectors) Less active phosphorylase “b” (subject to regulation by ATP, GTP, AMP)  
Liver phosphorylase (from a different gene than muscle) glycogenolysis Phosphorylase kinase, protein phosphatase I More active “a” Less active “b” contrast to muscle: neither form of liver phosphorylase is subject to allosteric regulation
Phosphorylase kinase muscle phosphorylase PKA (reverse= prot. phosphatase I) Fully active Inactive, and partially active with Ca++ Allows for Ca++ regulation during muscle contraction and with special epi receptors in liver that increase Ca levels
           
Glycogen Synthase (muscle and liver) duh Any kinase (incl. PKA), phosphatase Less active “b” (D) form More active “a” (I) form Allosteric + by G6P
           
Summary:  decreased glycogen synthesis and increased glycogen breakdown result from above reactions, stimulated by epinephrine in muscle and liver (plus by glucagon in liver)
           
PFK1 (muscle) Glycolysis proceed (F6Pà F16bP) Activated by F26bP     These are relevant because they’re analogous to liver reaction below and regulated by its product
FBPase1 (muscle) Gluconeogenesis (reverse of above) Inhibited by f26bP    
PFK2 (liver) F6PàF26bP These are actually the same enzyme-direction controlled by phosphorylation state (PKA, phosphatase)   Active Favored by high insulin, stimulating glycolysis via F26BP action on PFK1, which gives energy for FA synthesis
FBPase2 (liver) F26bPàF6P Active   Favored by > glucagon (low blood glucose), stimulates gluconeogenesis
           
Pyruvate Kinase (liver) Last step of glycolysis Kinase, phosphatase Less active More active Insulin favors activation of this enzyme; glucagon slows glycolysis
           
Acetyl CoA Carboxylase 1st committed step (using biotin) of FA synthesis, makes malonyl CoA AMP-activated kinase, phosphatase 2A Less active More active p.120 Allosteric regulation: (+) by citrate, (-) FA-CoA
           
Pyruvate dehydrogenase makes Ac-coA using 5 cofactors   Less active (Mg +2) More active (Ca+2)  

 

So just memorize this table right before the test.  Seriously, I hope it helps organize the info and makes it seem less overwhelming.  There are basically only two energy states-low and high, and these enzymes all fit into the grand scheme of trying to store it or mobilize it.

 

The important part is to understand that two antagonistic hormones (insulin and glucagon in rest, with the help of epinephrine under stress) can regulate all energy pathways in the body to avoid futile cycles and make sure all cycles are interlinked and pointing in the same direction.  Remember that hormonal controls generally override allosteric interactions and that no cycle is ever completely shut off (unless there are no substrates).