HMP Shunt, Fructose, Galactose Metabolism

Question 1

HMP Shunt:

3 Branches and starting products, rate limiting enzyme

Answer 1

Oxidative Branch: G6P

Non-Oxidative Forward: R5P

Non-Oxidative Reverse: F6P and G3P

rate limiting enzyme: G6PD

Question 2

HMP Shunt Oxidative Branch:

Starting substrates
Products
Enzymes & Regulation
Purpose

Answer 2

Starting substrate: G6P & NADP+

Products: NADPH & R5P

Enzymes:
G6PD

Regulation:
Activated by- increased [G6P and NADP+]
Inhibited by- NADPH

Purposes:
1. NADPH production for fatty acid synthesis, steroid synthesis, glutathione reduction in RBCs

2. Generate R5P for nucleotide synthesis

Question 3

Non-Oxidative Branch Forward

Starting substrate
Products
Enzymes
Regulation
Purpose

Answer 3

“Forward to F6P”

Starting Substrate: R5P

Products: Fructose6P and G3P

Enzymes:
-transketolase + TPP coenzyme

Regulation:
Not regulated, dependent on availability of TPP

Purpose:
1. R5P can be converted to glycolytic intermediates for oxidation

2. Provides mechanism for use of 5 C sugars

Question 4

Non-Oxidative Branch Reverse

Starting substrate
Products
Enzymes
Regulation
Purpose

Answer 4

“Reverse to R5P”

Starting substrate: F6P + G3P

Product: R5P

Enzymes: Transketolase + TPP

Regulation:
not regulated, dependent on TPP availability

Purpose: Glycolytic intermediates can be converted to R5P when need for NADPH is low

Question 5

Citrate and HMP Shunt

Answer 5

Citrate inhibits PFK-1 creating accumulation of G6P (upstream of PFK-1 Step in glycolysis)

G6P can then enter oxidative branch of HMP Shunt

Production of NADPH increases

Question 6

NADPH required for:

Answer 6

FA Synthesis
Cholesterol synthesis
Steroid synthesis
Glutathione reduction (H202 reduction)

Question 7

NADPH Derived from:

Answer 7

Malic Enzyme

HMP Shunt oxidative branch

tissue w/out mitochondria only use HMP shunt for NADPH production

Question 8

Glutathione reduction of H202

Answer 8

GSH donates SH group electrons to reduce H202 to H20

Glutathione become oxidized (GSSG)

NADPH donates electrons for reduction of GSSG back to GSH

NADPH INDIRECTLY supplies e- for H202 reduction

Question 9

Is Fructose entry to cells insulin dependent?

Answer 9

No.

Question 10

Fructose metabolic pathway

Answer 10

glycolysis, bypass PFK-1 step leading to increased rate

Question 11

Fructose metabolism

Answer 11

1. Fructose phosphorylated to F1P by Fructokinase (sugar trap in cell)
2. F1P cleaved by aldolase B to DHAP and D-glyceraldehyde
3. DHAP and Glyceraldehyde converted to G3P to enter glycolysis (fed) and lipogenesis

Question 12

Galactose matabolism

Answer 12

1. Phosphorylation of Galactose to Galactose1P by galactokinase (sugar trap)
2. Formation of UDP Galactose by Gal-1-P uridyltransferase
3. UDP Gal converted to epimer UDP-Glucose by UDP hexose 4 epimerase

UDP Gal can be used to synthesize lactose, glycoproteins, glycolipids and glycosaminoglycans

Question 13

Aldose rectuctase and galactose metabolism

Answer 13

Alsdose reductase has high km

when [galactose] is continuously high, aldose reductase converts galactose to galactitol

Galactitol detrimental for body