Gluconeogenesis

Question 1

What determines if pyruvate converts to lactate or vice versa

Answer 1

NADH/NAD ratio

Question 2

When you are in fasting state, is NADH higher or lower than NAD?

Answer 2

NADH will be lower which will drive lactate back to pyruvate and start gluconeogenesis

Question 3

Lactate is activated by which enzyme to make pyruvate? Then what happens to pyruvate?

Answer 3

LDH; it needs to be shuttled inside mitochondria

Question 4

How can pyruvate can enter mitochondria?

Answer 4

By a transport channel - pyruvate translocase

Question 5

When pyruvate enters the mitochondria, which enzyme works on it?
Why is this enzyme called an ABC enzyme?

Answer 5

Pyruvate carboxylase

Requires ATP for hydrolysis, biotin, and CO2

Question 6

What two other enzymes are considered ABC enzymes?

Answer 6

acetyl CoA carboxylase and propinyl CoA carboxylase

Question 7

In presence of pyruvate carboxylase, pyruvate gets converted to?

Answer 7

Oxaloacetate (intermediate of TCA)

Question 8

How does oxaloacetate get out of mitochondria into cytosol?

Answer 8

Shuttled via malate dehydrogenase (converts it to malate to get out then goes back to oxaloacetate)

Question 9

Then Oxaloacetate is worked on by __ to form?

Answer 9

PEPCK —> PEP (reversible)

Question 10

Fructose 6 phosphaste is converted to fructose 1,6 bisphosphate by what enzyme?
What enzyme does the other way around

Answer 10

PFK1

Fructose 1,6 bisphosphatase

Question 11

What activates PFK1 but deactivates fructose 1,6 bisphosphatase

What activates answer to be formed?

Answer 11

Fructose 2,6 bisphosphate

Insulin (activates PFK2 which is enzyme for answer)

Question 12

Where is the only location of glucose 6 phosphate
Glucose 6 phosphatase is only present where
Defect in this enzyme will lead to
Function of this enzyme in the liver?
When will this pathway happen?

Answer 12

ER
In liver and kidney (the only organs that form and release glucose)
Hypoglycemia - decreased blood glucose concentration
Allows the liver to supply the blood with free glucose
When you are exercising while fasted

Question 13

Which are the only amino acids that are completely ketogenic?
What does this mean?

Does acetyl CoA ever synthesize glucose?

Answer 13

Leucine and lysine
This means that these 2 AAs are the only AAs that cannot be degraded to TCA cycle intermediates

No - forms ketones

Question 14

Purpose of glucose alanine cycle

Answer 14

How proteins are used in synthesis of glucose in liver and kidney

Question 15

Triacylglycerols get phosphorylated to become ___ which gets oxidized to become ___

Answer 15

Glycerol-3-phosphate; DHAP (dihydroxyacetone phosphate) (an intermediate of glycolysis)

Question 16

A patient has a bacterial infection that produces an endotoxin that inhibits PEPCK. Under these condition, glucose production from what precursor will be inhibited?

Answer 16

Alanine (gives you pyruvate which needs to be activated by pyruvate carboxylase to give oxaloacetate which is acted on by PEPCK to make PEP)

Question 17

5 month old has seizures, delayed milestones, and muscle weakness. Workup reveals elevated serum levels of lactate, alanine, pyruvate and ketoacids. Pyruvate carboxylase activity is markedly decreased. The abnormality may be due to deficiency of which vitamin?

Answer 17

Biotin because this is an ABC enzyme

Question 18

What enzymes are the correct short term regulators of gluconeogenesis:

1. Obligatory regulation
2. Allosteric regulation
3. Covalent modification

Answer 18

1. Pyruvate carboxylase
2. Fructose 1,6 bisphosphatase
3. PFK2 and pyruvate kinase

Question 19

Long term regulating enzyme of gluconeogenesis for induction and repression?

Answer 19

PEPCK

Question 20

When there are high levels of Acetyl CoA, TCA cycle needs to be slowed. What does acetyl CoA activate and inhibit in order to do this?

Answer 20

Activates pyruvate carboxylase

Inhibits PDH

Question 21

Protein kinase A mediates phosphorylation of what two things?

This has to do with covalent modification of ?

Answer 21

Pyruvate kinase and PFK2

Glucagon (high glucagon activates protein kinase A)