BCH2022 Study Guide - Final Guide: Pentose Phosphate Pathway, Malate Dehydrogenase, Pyruvate Carboxylase
25 May 2018
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Biosynthesis of Carbohydrates
Pathways in Cytosol:
• Glycolysis
• Pentose phosphate pathway
o NADPH production
• Fatty acid synthesis
Pathways in Mitochondrial Matrix:
• Citric acid cycle
• Oxidative phosphorylation
• Beta-oxidation of fatty acids
• Ketone-body formation
Both Cytosol and mitochondria
• Gluconeogenesis
• Urea synthesis
Endoplasmic Reticulum
• Phospholipid synthesis
• Sterol synthesis
• Fatty acid synthesis: elongation, desaturation
How is glucose metabolism regulated in the body?
• Constant supply of glucose is maintained at ~5 mmol/L in human blood to
supply the brain and erythrocytes
• Blood glucose levels maintained by liver and co-ordinately regulated by
pancreatic hormones: insulin and glucagon
• Glucose enters blood in three major ways
1. Absorption from the intestine
2. Release of glucose from glycogen in liver
3. Release of glucose from liver following gluconeogenesis
• Fuel
o Sprinting: anaerobic exercise → lactate
o Distance running: aerobic exercise → CO2
▪ Complete oxidation of muscle and liver glycogen (ATP
generated even slower)
o Most of the body’s glucose can by supplied by glycolysis in the liver
Gluconeogenesis
• Location: cytosol of liver
o Sometimes cortex of kidneys
• Occurs during periods of fasting, starvation, low carbohydrate diets or intense
exercise
• Function: maintaining blood glucose levels
• Metabolic pathway that results in generation of glucose from non-
carbohydrate carbon substrates: glycerol, lactate, amino acids, pyruvate
o Makes glucose for blood
• 2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 4H2O → glucose + 4 ADP
+ 2 GDP + 6Pi + 2NAD+
• 3 bypass steps (irreversible)
o Bypass 1
▪ Pyruvate → oxaloacetate → phosphoenolpyruvate (PEP)
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▪ Products: 2 GTP, 2 ATP
o Bypass 2
▪ Hydrolysis of fructose 1, 6-bisphosphate → fructose 6-
phosphate
o Bypass 3
▪ Hydrolysis of glucose 6-phosphatase → glucose + Pi
How is it regulated?
• Key regulatory enzyme: phosphofructokinase (PFK)
o Enzyme: fructose 1,6 bisphosphatase
• Glycolysis and gluconeogenesis are reciprocally regulated (when one is on
and other is off)
Synthesis of Glucose from:
1. Pyruvate
Bypass 1
• Pyruvate (2 molecules) → oxaloacetate (→ malate → oxaloacetate) →
phosphoenolpyruvate (PEP)
• Enzyme: Pyruvate carboxylase (mitochondria)
o Coenzyme: biotin (CO2 carrier)
• Cofactor: ATP
o Produces: ADP + Pi
• Malate shuttle
o Oxaloacetate requires shuttle system to transport it out of
mitochondria → malate
o Enzyme: malate dehydrogenase (mitochondria)
▪ Cofactor: NADH
o Malate → oxaloacetate (cytosol)
▪ Cofactor: NAD+
• When making glucose: make sure a lot of NADH in cytosol otherwise
reverse reaction of step 6 glycolysis will stop
• Oxaloacetate → phosphoenolpyruvate
o Enzyme: PEP carboxykinase
o Phosphate groups phosphorylate
• Allosteric activation: important physiological control mechanism
o Molecules binding onto sites other than active site of other
enzymes to change enzyme kinetics
• Fates of pyruvate:
o Pyruvate → acetyl-CoA → CAC (low levels of ATP)
o Pyruvate → oxaloacetate → Gluconeogenesis (high levels of
ATP)
Bypass 2
• Fructose 1,6 Bisphosphate → Fructose 6 phosphate
• Enzyme: fructose 1,6 bisphosphatase
• Cofactor: H2O → Pi
• Regulatory enzymes
o Stimulated by ADP, AMP
o When used a lot of ADP, AMP → energy poor
find more resources at oneclass.com
find more resources at oneclass.com
