s3. Pyruvate is converted to phosphoenolpyruvate(PEP)via two alternative paths In both paths, pyr uvate is converted to oxaloacetate with the catalysis of pyruvate carboxylase)in mitochondria In one path, oxaloacetate is converted directly to PEP in the matrix of mitochondria in a reaction catalyzed by the mitochondrial PEP carboxykinase isozyme, PEP is then transported to the cytosol for further conversion
3. Pyruvate is converted to phosphoenoylpyruvate (PEP) via two alternative paths • In both paths, pyruvate is converted to oxaloacetate (with the catalysis of pyruvate carboxylase) in mitochondria. • In one path, oxaloacetate is converted directly to PEP in the matrix of mitochondria in a reaction catalyzed by the mitochondrial PEP carboxykinase isozyme, PEP is then transported to the cytosol for further conversion
In another path, oxaloacetate is first converted to malate in the matrix, which is, then transported to the cytosol. where it is converted to oxaloacetate and then PEP in a reaction catal yzed by cytosolic PEP carboxykinase isozyme Both paths involve a carboxylation decarboxylation sequence, acting as a unique way to activate pyruvate Two high-energy phosphate equivalents must be expended to convert one pyruvate to one PEP
• In another path, oxaloacetate is first converted to malate in the matrix, which is then transported to the cytosol, where it is converted to oxaloacetate, and then PEP in a reaction catalyzed by cytosolic PEP carboxykiase isozyme. • Both paths involve a carboxylationdecarboxylation sequence, acting as a unique way to activate pyruvate. • Two high-energy phosphate equivalents must be expended to convert one pyruvate to one PEP
PEP From pyruvate Bicarbonate Pyruvate cytosolic PEP to PEP: two HO-C+ CH3-C Oxaloacetate alternative paths ATP NADH+H+ pyruvate cytosolic arboxylnse biotin malate ADP P NAD+ Malate Oxaloacetate Malate PEP NAD+ Oxaloacetate mitochondrial PEP CC-CH2*C-C NADH+H+ carboxykinase Oxaloacetate Oxaloacetate pyruvate carboxylase pyruvate CO rboxylase cO Guanosine 0-P-0-P-0-P-O Pyruvate TP Mitochondrion Cytosol →GDP PEP Pyruvate carboxykinase NADH +H+ 03 lactate dehydrogenase CH,=C-Coo NAD+ Phosphoenolpyruvate Lactate b)
From pyruvate to PEP: two alternative paths
24. Conversion of fructose 1, 6 bisphosphate to fructose 6-phosphate is the second bypassing step The reaction is catalyzed by Mg 2+ -dependent fructose 1, 6-bisphosphatase (instead of phosphofructokinase Fructose-1, 6-bisphosphate H20- fructose-6-phosphate Pi △G° 16. 3 kJ md
4. Conversion of fructose 1,6- bisphosphate to fructose 6-phosphate is the second bypassing step • The reaction is catalyzed by Mg 2+ -dependent fructose 1,6-bisphosphatase (instead of phosphofructokiase-1)
5. The conversion of glucose 6-phosphate to glucose is the last bypassing step The reaction is catalyzed by glucose 6-phosphatase instead of hexokinase). The enzyme is present on the lumen side of the ER membrane of hepatocytes and renal cells The enzyme is not present in muscle or brain cells, where gluconeogenesis does not occur coe6 phosphate+H2O—→ glucose+P1△G=-13.8 kJ/mol
5. The conversion of glucose 6-phosphate to glucose is the last bypassing step • The reaction is catalyzed by glucose 6-phosphatase (instead of hexokiase). • The enzyme is present on the lumen side of the ER membrane of hepatocytes and renal cells. • The enzyme is not present in muscle or brain cells,where gluconeogenesis does not occur