Glycolysis and ETC Flashcards
Glucose Transporters:
(Tissue, Km, Features)
GLUT1
Tissue: Brain, RBCs, placenta, fetal tissue
Km: low
Efficient binding allows constant uptake of glucose
Glucose Transporters:
(Tissue, Km, Features)
GLUT2
Tissue: Liver, kidney, intestines, pancreatic B-cells
Km: high
glucose export by the liver & glucose sensor for pancreatic B cells
Glucose Transporters:
(Tissue, Km, Features)
GLUT3
Tissue: Brain
Km: Low
Very efficient binding gives preferential uptake during hypoglycemia
Glucose Transporters:
(Tissue, Km, Features)
GLUT4
Tissue: Muscle, adipose
Km: Medium
INSULIN SIGNALING recruits GLUT4 to cell surface during fed state to increase uptake
Fed State: Absorptive Phase in Liver
I/G ratio, time since meal, energy producing, CHO storage and lipid storage pathways
High I/G
0-4 hours after mixed meal
Energy producing (First Priority):
- Glycolysis
- TCA cycle
- ETC & ATP Synthase
CHO Storage (Second Priority): -Liver glycogenesis
Lipid Storage (third priority): -lipogenesis (FA synth + TAG synth)
Glycolysis Activity in Fed & Fasting States for:
Liver, Muscle, Adipose, Brain/RBC
FED: All tissues oxidize glucose
FASTING: only brain and RBCs since they can’t oxidize FFAs
A. Where does glycolysis occur?
B. Where does ATP, GTP and reduced e- carrier production occur?
C. Where does most NADH production occur?
A. Cytoplasm
B. Cytoplasm and mitochondrial matrix
C. Mitochondria
Net energy production of Glycolysis:
2 ATP, 2 NADH (shuttle e- to ETC)
Glycolysis:
- Starting substrate & End Product
- Location
- Enzymes
- Purpose
Glucose–>Pyruvate
Location: Cytoplasm
Enzymes:
-Glucokinase (liver)/Hexokinase (muscle, fat)
- PFK-1 (Rate limiting)
- Pyruvate Kinase
Purpose:
- NADH + ATP production
- Generation of intermediates for other pathways (i.e. pyruvate, ACoA, lactate)
Glucokinase:
- Step active
- Function
- Km
- Vmax
- Regulation
Step active:
-Glucose–> G6P (liver)
Function:
- Sugar trap for hepatocyte
- Phosphorylates glucose to G6P (neg charge) so it cannot cross membrane
- Removes large amount of glucose from portal blood
Km/Vmax:
-High Km and Vmax
Regulation:
-synthesis increased by insulin
Hexokinase:
- Step active
- Function
- Km
- Vmax
- Regulation
Step active:
-Glucose–> G6P (other tissue)
Function:
- Sugar trap
- Phosphorylates glucose to G6P (neg charge) so it cannot cross membrane
- works even during fasting state
Km/Vmax:
-Low Km and Vmax (high affinity)
Regulation:
- Synthesis increased by insulin
- Inhibited by G6P
PFK-1
- Step active
- Function
- Regulation
Step Active:
F6P–>F1,6BP
Function:
- activated by F6P metabolite F2,6BP
- F2,6BP binds to PFK-1, increasing activity
- Fasting state, F2,6BP levels decrease via dephosphorylation, PFK-1 activity decreased
Regulation:
- Activators: F2,6BP, AMP
- Inhibitors: ATP, citrate
- Synthesis increased by high I/G
NOT REGULATED DIRECTLY BY PHOSPHORYLATION
Pyruvate Kinase (PK)
- Step active
- Regulation
Step Active: FED STATE
-PEP to Pyruvate
Regulation:
1. Activated by F1,6BP via “feed forward”
- Rule of Thumb phosphorylation
- High I/G: Dephosphorylated and ACTIVE
- Low I/G: phosphorylated by PKA and INACTIVE - [PK]
- Insulin increases PK synthesis
- Glucagon decreases PK synthesis
Oxidation of Pyruvate:
- Location
- Starting substrate & End Product
- Enzymes
- Purpose
Pyruvate–> Acetyl CoA
Location: cytoplasm, can be imported to mitochondria via transporter
Enzyme: PDHC
Purpose: generate ACoA for TCA cycle or FA synthesis
PDHC:
- Features
- Function
- Coenzymes and precursors
- Regulation
Pyruvate –> ACoA
Features:
-mitochondrial protein complex, 3 enzymes 5 coenzymes
Coenzymes & Precursors:
- TPP & Thiamine (B1)
- FAD & Riboflavin (B2)
- CoA and Pantothenate (B5)
- NAD+ & Niacin (B3)
- Lipoic Acid
Function:
-Turns Pyruvate to ACoA, creates NADH
Regulation:
- Inhibited by high [ACoA and NADH]
- Fasting state, accumulation of NADH and ACoA from beta oxidation