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Gluconeogenesis. Synthesis of "new glucose" from common metabolites Humans use ~160 g of glucose per day 75% is used by the brain Body fluids contain only 20 g of glucose Glycogen stores yield 180-200 g of glucose So the body must be able to make its own glucose
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Glucose (6C) to 2 pyruvates (3C)
Creates energy 2ATP
Reduces 2 NAD+ to 2 NADH
Active when energy in cell low
10 steps from glucose to pyruvate
Pyruvate to AcCoA before Krebs
2 pyruvates (3C) to Glucose (6C)
Consumes energy 4ATP+2GTP
Oxidizes 2NADH to 2 NAD+
Active when energy in cell high
11 steps from pyruvate to glucose
AcCoA isn’t used in gluconeogenesisGlycolysis vs Gluconeogenesis
Gluconeogenesis uses 7 of the 10 enzymatic reactions
of glycolysis but in the reverse direction. The 3 not used
are the ones requiring ATP in glycolysis.
- recall that pyruvate is the final product of glycolysis.
The pyruvate carboxylase reaction.
It is an essential vitamin in the human diet, but deficiencies are rare.
Avidin, a protein found in egg white binds tightly to biotin and excessive consumption of raw egg white can lead to biotin deficiency.
Oxaloacetate cannot be transported directly across the mitochondrial membrane so it is converted to malate, then transported, then oxidized back to oxaloacetate.
Fig. 18-26, p. 595
Fig. 18-23, p. 594
Isomerase: An enzyme that catalyzes the transformation of compounds into their positional isomers. In the case of sugars this usually involves the interconversion of an aldose into a ketose, or vice versa.
Kinase: An enzyme that catalyzes the phosphorylation (or dephosphorylation) of a molecule using ATP (or ADP).
Mutase: An enzyme that catalyzes the transposition of functional groups, such as phosphates, sulfates, etc.
Fig. 18-20, p. 593
Triose phosphate isomerase
Fig. 18-14, p. 589
4th reaction of glycolysis (7th reaction of gluconeogenesis).
Reversible reaction also used in gluconeogenesis.
An aldol cleavage reaction (the reverse of an aldol condensation).
Glucose-6-phosphatase is subject to substrate level control.
- at higher G6P concentrations reaction rate increases
- recall, this happens in the liver. Other tissues do not hydrolyze their G6P, thereby trapping it in the cells.
Glycolysis and gluconeogenesis are reciprocally regulated.
- regulatory molecules that inhibit gluconeogenesis often activate glycolysis, and vise versa.
- activates phosphofructokinase.
- inhibits fructose-1,6-bisphosphatase.
- its synthesis and degradation are catalyzed by the same bifunctional enzyme.
Fructose-2,6-bisphosphate activates glycolysis and inhibits gluconeogenesis, so its level is very important.
TCA cycle intermediates
Most amino acids
Not substrates for gluconeogenesis: