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Biochemistry- Gluconeogenesis


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Gluconeogenesis is
the formation (biosynthetic process) of glucose from non-carbohydrate precursors.
What is important to remember about biosynthetic processes and their counterpart biodegradation?
Biosynthetic processes are NEVER simply the reversal of the correspinding catabolic reaction.
Why is gluconeogenesis so important if we can synthesize molecules for energy such as tryglycerols, pyruvates and various sugars?
The brain and CNS can ONLY use glucose as its energy source. Other organs including medulla of the kidneys, testes, erythrocytes can also only use glucose.
Most gluconeogenesis occurs where?
in the cytosol of liver and kidney cells. Some reactions take place inside the mitochondria of these cells and then the products are transported out to the cytosol.
Biosynthesis of glucose (gluconeogenesis) uses what:
3 to 4 carbon precursors like LACTATE, and alanine (amino acid).

*Lactate might be important as a fate of anaerobic glycolysis.*
If glycolysis is highly exergonic and gluconeogenesis is essentially glycolysis in reverse how is it that gluconeogenesis can occur?
The three steps of glycolysis that are highly exergonic, are catalyzed by other enzymes by different processes. these three include those steps catylized by hexokinase, phosphofructokinase and pyruvate kinase. (ATP yielding reactions).
what are the three enzymes that differ between glycolysis and gluconeogenesis and their glycolytic counterparts?
glycolysis==> gluconeogenesis

Hexokinase==> glucose6-phosphotase
Phosphofructokinase====> Fructose 1, 6 bisphosphotase
Pyruvate kinase ======> Pyruvate carboxylase
Step 1 of Gluconeogenisis...
Occurs in the mitochondrial matrix. using ATP pyruvate is carboxylated to oxaloacetate by pyruvate carboxylate.
What are two important things to remember of step 1 in gluconeogenesis?
1.) it forms NAD from NADH to replinish the NAD used in the G3P step of glycolysis.

2.) Oxoaloacetate CANNOT be transported to the cytosol (and the enzyme which makes it is only found in the mitochondrial matrix).
Once Pyruvate carboxylase converts oxaloacetate to malate and it is transfered out of the mitochondria then what?
Malate is reoxidized to oxaloacetate by malate dehydrogenase.

Then phosphoenyl pyruvate carboxykinase (PEPCK) along with energy from GTP convert the oxaloacetate to phosphoenyl pyruvate (second to last step of glycolysis).
What is the net equation for gluconeogenesis:
2 pyruvate + 4 ATP + 2 GTP + 2 NADH ====> Glucose + 4 ADP + 2 GDP + 2 NAD+ + 6 inorganic phosphates (Pi)
The pyruvate carboxylase responsible for converting pyruvate to oxaloacetate requires ________ as a cofactor, is found only _______,
biotin; in the mitochondrial matrix
The fructose 1, 6 bisphosphate step is analagous to the phosphofructo kinase step of glycolysis in that...
At this step in both pathways there is HIGH REGULATION of the pathway.
Glucose 6 phosphate the enzyme required for the final conversion of Glucose 6 phosphate to Glucose is not found where...
in the muscles and the brain there is no glucose 6 phosphate. Thus these cells release NO FREE GLUCOSE. they use all of it. (they need it, especially the brain).
What is the energy cost of gluconeogenesis in terms of ATP?
there is a loss of 12 ATP's to synthesize glucose. However alot of the carbon to from glucose was from the conversion of lactate to glucose which generates 6 ATP. therefore the net loss of ATP of gluconeogenesis is said to be 6 ATP.

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