Gluconeogenesis

Question 1

What is gluconeogenesis?

Answer 1

Synthesis of glucose from mostly non-carbohydrate sources (Ex: pyruvate, lactate, glycerol, certain amino acids)

Question 2

What is the glucose alanine cycle?

What is the cori cycle?

Where do these processes occur?

When are they necessary?

What will drive the cori cycle in muscle?

Answer 2

• Occur between muscle and liver
• Pyruvate in muscle is converted to alanine or lactate, travels through the blood to the liver where it is converted back to pyruvate and used for gluconeogenesis to regenerate glucose
• Necessary in anaerobic respiration, when the rate of glycolysis in the muscle tissue outpaces the pace of the TCA cycle.
• Cori cycle is used to convert pyruvate to lactate and regenerate NAD+ that is used for glycolysis. Occurs when there is an excess of NADH that inhibits the OxPhos and TCA cycle flux

Question 3

What is the major substrate for TCA in gluconeogenesis?

Answer 3

Oxaloacetate

Question 4

What cells express glucose 6 phosphatase?

Answer 4

Only cells that perform gluconeogenesis (liver and kidney)

Question 5

What vitamin is essential for pyruvate carboxylase’s function?

Answer 5

Biotin

Question 6

High levels of NADH have what effect on the malate shuttle for OAA? What solution do hepatic cells have to deal with this problem.

Answer 6

They inhibit the conversion of malate to OAA in the cytosol. This would result in the halting of gluconeogenesis b/c OAA is needed in the cytosol to generate PEP for gluconeogenesis. As a result, hepatocytes can turn lactate into pyruvate and then convert –> OAA –> PEP all in the mitochondria. PEP can then be transported out of the mitochondria and used for gluconeogenesis.

Question 7

The enzyme glucose 6 phosphatase is the enzyme in gluconeogenesis and it converts Glu6P to Glu. Where is this enzyme located and why?

Answer 7

It is located in the ER membrane. Thus, when Glu6P is made in the cytosol, it must be transported into the ER where Glu6Phosphatase will remove phosphate and produce glucose, which then is transported out of ER to cytosol for distribution to bloodstream. The reason for this is because physical separation is needed to avoid a futile cycle. If G6phosphatase were in cytosol, it could generate glucose and then glucokinase could act on glucose to turn it back into glu6P.

Question 8

Explain how consumption of alcohol in a fasted state can lead to hypoglycemia and fatty liver.

Answer 8

Hypoglycemia

Oxidation of ethanol by alcohol dehydrogenase generates a lot of NADH. High levels of NADH inhibits glycolysis and the TCA cycle. Thus, any pyruvate that is made will accumulate and instead be converted to lactate in order to regenerate NAD+ to allow these cycles to continue. If the individual is not taking in glucose from their diet, then the body will want to generate glucose but it won’t be able to generate sufficient glucose because the pyruvate was used to generate lactate and NAD+. This will result in hypoglycemia.

Fatty Liver

The conversion of DHAP to Glyceraldehye 3-phosphate (catalyzed by TIM) uses NADH. In an environment with high [NADH], this reaction will be driven forward to generate a lot of Glyc-3-P. This can be used for fatty acid biosynthesis, which results in an increase in triglycerides stored in the liver.