M5 - Gluconeogenesis, Lactic Acidosis

Question 1

Overall Reaction, Gluconeogenesis

Answer 1

-6 ATP “equivalents” are required
* Fatty acid oxidation is a major source ATP
* NAD+ must be reduced to NADH
-depends on precursors used to make pyruvate

Question 2

Location

Answer 2

Mostly in the liver, with kidney playing a secondary role
* Nine enzymes located in the cytosol
* One enzyme in the mitochondria
* One enzyme in the ER

Question 3

____ concentration gradient determines direction

Answer 3

Glucose

Question 4

• Impaired gluconeogenesis can cause fasting ____
• Inappropriate gluconeogenesis can cause fasting ____

Answer 4

• hypoglycemia
• hyperglycemia

Question 5

Four Key Enzymes

Answer 5

1. Glucose-6 Phosphatase (G6Pase)
2. Fructose 1,6 bisphosphatase-1 (FBPase-1)
3. PEP Carboxykinase (PEPCK)
4. Pyruvate Carboxylase

Question 6

Major Precursors Used to Make Pyruvate

Answer 6

-Lactate is taken up by the liver and oxidized to pyruvate in cytosol by LDH
-Alanine is taken up by the liver and transaminated to pyruvate by ALT

Question 7

Mechanisms to regenerate NADH

Answer 7

Oxidation of lactate to pyruvate via LDH
-aspartate used as precursor to OAA

Oxidation of malate to OAA via MDH
-malate used as precursor to OAA

Question 8

Allosteric Regulation of
Gluconeogenesis

Answer 8

• AMP and F2,6 BP inhibit FBPase-1
• Acetyl CoA activates pyruvate carboxylase

Question 9

Regulation by PKA

Answer 9

Less F2,6 BP
-Decrease glycolysis and increase gluconeogenesis

Question 10

Regulation by AMPK

Answer 10

More F2,6 BP
-Increase glycolysis and decrease gluconeogenesis

Question 11

Gluconeogenesis promotes hepatic glucose ____

Answer 11

Production

Question 12

Glycolysis promotes hepatic glucose ____

Answer 12

Uptake

Question 13

____ increases protein phosphatases that reverse the effects of PKA

Answer 13

Insulin

Question 14

Glucagon increases ____

Answer 14

PKA (decreases F26)

Question 15

Decreases Lactate Removal

Answer 15

1. Liver disease
2. Increase NADH/NAD+
3. defects in gluconeogenesis
4. metformin

Question 16

In therapeutic doses, metformin minimally ___ plasma lactate because kidneys remove the small amount of excess lactate

Answer 16

Increases

Question 17

In patients with decreased kidney function, plasma metformin increases (exaggerating its effects on lactate balance) and renal lactate clearance ____

Answer 17

Decreases

Question 18

In patients with tissue hypoxia (e.g. cardiorespiratory insufficiency), increases in lactate production can be enough to cause ___

Answer 18

Lactate Accumulation

Question 19

In patients with liver disease or excessive alcohol use, hepatic lactate ____ is further impaired enough to cause lactate to accumulate

Answer 19

Clearance