Lecture 3 (W2) - Gluconeogenesis

Question 1

What is gluconeogenesis?
Is it a catabolic / anabolic pathway?

Answer 1

Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources. It is the opposite from glycolysis, and is an anabolic pathway.

Question 2

When does gluconeogenesis occur?

Answer 2

When glucose levels in body is low, but body needs to utilise glucose for energy

Question 4

What is the starting substrate / precursors for gluconeogenesis?[4]

Answer 4

1. Pyruvate
2. Lactate (can be oxidised into pyruvate)
3. Gluconeogenic amino acids (alanine) – can be converted into pyruvate
4. Glycerol (converted into G-3-P and DHAP…)

Question 5

The breakdown of glycogen → glucose is also considered gluconeogenesis. True or False?

Answer 5

False !! Glycogen is from a carbohydrate source but gluconeogenesis is from non-carb source!!

Synthesis of glucose form glycogen is known as glycogenesis

Question 6

What are the 2 main tissues that synthesize glucose?

Answer 6

• Liver (~90%)
• Kidney (~10%)

Question 7

In glycolysis, there are 3 irreversible steps :
Step 1 : glucose → G6P (hexokinase)

Step 3 : F6P → F-1,6 BP (phosphofructokinase)

Step 10 : phosphoenolpyruvate (PEP) → pyruvate (pyruvate kinase)

In gluconeogenesis, how are these irreversible steps regulated (Steps 1 and 3), and how is Step 10 bypassed in gluconeogenesis?

Answer 7

• The enzymes involved in step 1 and 3 are allosterically regulated.

For Step 10, to convert pyruvate back into PEP, the reaction is bypassed by :
- converting pyruvate into oxaloacetate in the mitochondria
- then conversion of oxaloacetate back into PEP in the cytosol

Question 8

Since gluconeogenesis is the opposite from glycolysis, the irreversible reactions are as follows :

Step 1 : G6P → glucose

Step 3 : F-1,6 BP → F6P

Step 10 : pyruvate → phosphoenolpyruvate (PEP)
- pyruvate → oxaloacetate
- oxaloacetate → PEP

What are the names of the enzymes catalysing these steps?

Answer 8

Step 1 : G6P phosphatase

Step 3 : F-1,6 BP phosphatase
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Step 10
- pyruvate (3C) → oxaloacetate (4C) : Pyruvate carboxylase ;; addition of COOH group
- oxaloacetate (4C) → PEP (3C) : **PEPCK, phosphoenolpyruvate carboxykinase **

Question 9

During starvation, after glycogen reserves are exhausted, what happens to maintain energy in the body?

Answer 9

Proteins from the muscle are broken down, and glucogenic amino acids (~30% in the form of alanine) are used to produce energy.

Question 10

When converting PEPCK into pyruvate, it occurs in a 2-step process : PEP → oxaoacetate → pyruvate. What is the regulation strategy for the conversion of PEP into pyruvate, and how does the cellular location of PEPCK affect this process?

Answer 10

Regulation strategy : access to substrates
- oxaloacetate synthesis from PEP occurs in the mitochondria
- however, to convert oxaloacetate into pyruvate, some cells only have PEPCK enzyme in the cytosol. Thus, oxaloacetate has to be converted into malate / aspartate and be transported through the mitochondrial shuttles, before being converted back into oxaloacetate and then into pyruvate in the cytosol.

Question 11

Another regulation strategy to regulate glycolysis and gluconeogenesis is through hormones such as insulin and glucagon. How do these hormones regulate blood glucose?

Answer 11

• Insulin : encourages uptake of glucose by muscle cells and conversion into glycogen when there is excess glucose in bloodstream (fed conditions)
• Glucagon : stimulates cells to convert glycogen into glucose in starvation mode.