eric niederhoffer siu-som
DESCRIPTION
Regulation of Phosphofructokinase-1: Too Much of a Good Theme?. Eric Niederhoffer SIU-SOM. Problem-based learning using electronic patient cases Organ-system, integrated disciplines Specific example - diabetes mellitus/alcoholic ketoacidosis Learning Issues - PowerPoint PPT PresentationTRANSCRIPT
Eric NiederhofferSIU-SOM
Regulation of Phosphofructokinase-1: Too Much of a Good Theme?
Curriculum Context• Problem-based learning using electronic patient
cases• Organ-system, integrated disciplines• Specific example - diabetes mellitus/alcoholic
ketoacidosis• Learning Issues
Which steps in metabolic pathways are
regulated by insulin, glucagon, or other
important hormones or metabolites?
How do insulin and glucagon balance the
degradation, synthesis, and storage of glucose?
How does the regulation of glycolysis compare
between liver, cardiac muscle and skeletal
muscle?
PK
PFK-1
Glc
Acetyl-CoA
Pyr
F6P
F16BP
PEP
G6P
PDH
F26BPasePFK-2
Glycolysis: Regulatory Steps
HK
InsulinGlucagon
Ep
Adipose
HeartLiver
GK
Liver
Liver
Liver
Heart
NH4+
AMPPi
PFK-1
Glc
F6P
F16BP
G6P
PFK-2
F26BP
ATPCitrate
PEPH+
Regulation Focus
PFK-1 - Facts
• Two genes - PFKL (21q), PFKM (12q)
• Tetramer - muscle (M4), liver/kidney (L4),
platelet (M4, M3L, M2L2, ML3, L4)
• T and R states
• Activators - AMP, ADP, cAMP, Pi, F6P,
F16BP, F26BP, NH4+
• Inhibitors - ATP, citrate, PEP, H+
• Interaction with renal H+ ATPase• Glycogen storage disease VII (Tauri) -
autosomal recessive, gout, increased O2
affinity (decreased 23BPG)
PFK-2 - Facts
• Four genes - PFKFB1 (X), PFKFB2 (1),
PFKFB3 (10), PFKFB4 (3)• PFK-2 dimer• Bifunctional protein (PFK/F26BPase)• Activators/inhibitors - similar to PFK-1
except no ATP inhibition• Brain no (or low) mRNA detected• Skeletal muscle - F6P regulates• Phosphorylation - liver (Ser32, N term),
cardiac (Ser406[466,483],Thr475,
F26BPase)
F26BPase-PFK-2 Regulation Comparison
F26BPase-PFK-2
F26BPase-PFK-2P
Insulin
PrPase2A
GlucagonEp
PKALiver
F26BPase-PFK-2
F26BPase-PFK-2F6P↑F6P↓Skeletal
Muscle
F26BPaseP-PFK-2
F26BPase-PFK-2
???PKA
Ep
Insulin
AMPK/AKT/WISKHeart