-
Glucose Transporters
- GLUT2 pancreas liver, high Km, proportional plasma conc
- GLUT3 brain-Low Km
- GLUT4 muscle adipose, insulin sensitive
-
Glucokinase (GK)
- glucose->G6P F6P
- liver pancreatic(beta) cells
- amplified by nucleus translocation
- glucose sensor-> high Km (other cells have hexokinase with low Km)
-
Glycolysis Control Points
- 2 of 8 steps irreversible
- upregulators-AMP, F2,6-BP
- inhibitors-ATP, citrate, alanine, G6P, H+
- 1. PFK-phosphofructokinase
- G6P->F1,6BP
-
Glucagon
- increses cAMP-PKA in liver
- phosphorylates bifunctional PFK-2 to decrease F26BP
- phosphorylates Pyruvate Kinase->stop glycolysis
- INHIBITS GLYcOLYSIS
-
Pyruvate Dehydrogenase
- PDH
- pyruvate->Acetyl CoA
- inhibited by NADH, acetyl CoA, ATP, glucagon(phosphorylated=inactive)
- upreg by Ca2+
-
Citric Acid Regulators
- Pyruvate dehydrogenase-- inhibited by NADH, ATP, acetyl CoA2)
- Isocitrate dehydrogenase--inhibited by NADH and ATP3)
- Alpha-ketoglutarate dehydrogenase-- inhibited by NADH, ATP, succinyl CoA
-
Gluconeogenesis
- liver function
- During fast, substrates for gluconeogenesis provided by peripheral tissues
- (adipose->glycerol)
- (RBC->lactate)
- (muscle->alanine)
- downregulator ADP
- Enzymes
- 1. Pyruvate Carboxylase (pyruvate->oxaloacetate)
- 2. PEPCK (oxaloacetate-->PEP)
- 3. F1,6 BPhospatase (+citrate) (-AMP, F26BP)
- 4. G6Phosphatase->allows export of glucose to other tissues
- Requires 6 ATP (pyruvate->glucose)
-
G6Phosphatase
- allows liver to provide glucose to other tissues
- lumen of the endoplasmic reticulum
- Requires 5 proteins
- G6P transporter-- takes G6P into ER
- Calcium-binding stabilizing protein (SP)
- G6 Phosphatase
- Glucose transporter-- bring glucose back out of the cell
- Phosphate transporter-- bring phosphate back out of the cell
-
Van Gierke disease
- Glycogen storage disease, sever fasting hypoglycemia
- used to be infusion, now uncooked starch
-
Glycogen Sythase
- unphosphorylated=ACTIVE
- UPREG G6P
-
Glycogen phosphorylase
- glycogenolysis
- activated by phosphorylation +glucagon(liver), +epinephrine (muscle)
- dephosphorylation catalyzed by protein phosphatase 1, stimulated by insulin [non-phosphorylated = ACTIVE
- inhibited G6P, ATP, Glucose
- upreg Calcium, AMP
-
acetyl CoA carboxylase
- connects glycolysis to lipogenesis
- Catalyzes the first and rate-limiting step of fatty acid synthesis
- The formation of malonyl CoA
- citrate->enzyme from inactive dimer->active polymer
- inhibited by existing long chain fatty acyl CoA
- Glucogon, epinephrine phosphorylate ACC (inactivate)
- Insulin remove phosphatae to make ACC active
-
Insulin present in FED STATE
- INCREASE
- Glucose uptake
- Glycolysis (liver)-- liver doesn glycolysis for itself when times are good because it doesn't have to supply for other tissues
- Glycogen synthesis
- Fat synthesis
- ==============
- DECREASE
- Gluconeogenesis
- Glycogen breakdown
- Lipolysis
- Ketogenesis
-
Glucagon and epinephrine present in FASTED STATE
- INCREASE
- Gluconeogenesis
- Glycogen breakdown
- Lipolysis
- Ketogenesis
- ============
- DECREASE
- Glycolysis (liver)
- Glycogen synthesis
- Fat synthesis
-
Pentose Phosphate Pathway
- "pentose shunt" or "hexose monophosphate" shunt
- G6P dehydrogenase is an important enzyme!
- Synthesis of pentose sugars for DNA, RNA, ATP, NADH, FAD
- Generate NADPH from NADP+ for biosynthetic reactions
- Minor functions
- Interconversion of 3, 4, 5, 6 and 7 carbon sugars1)
- Generate glycolytic intermediates2)
- Rate is controlled by levels of NADP+
-
G6P patways
- glycogenolysis
- pyruvate
- 6phosphoglucanate->Ribose 5 phospate
-
NADPH
- Biosynthesis of Fatty acids, Cholesterol, Neurotransmitters, Nucleotides
- Detoxificationi
- Reduction of oxidized GSH in erythrocytes: Keeps hemoglobin iron in a ferrous state, Stabilizes erythrocyte membrane
- Glutathione is a peptide that keeps redox potential within the cell
-
Glucose 6-phosphate dehydrogenase
- First step in pentose phosphate pathway
- Required for generation of NADPH in erythrocytes
- Hemolytic anemia
- Many people in world (200 million) that have G6P dehydrogenase that is ineffective
- RBCs may get these Heinz bodies that are denatured proteins,
- May confer selective advantage against malaria parasite
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