Polyol Pathway

Question 1

What is the polyol pathway do?

Answer 1

It converts glucose to a polyol (sorbitol) by reduction of the aldehyde group which produces an additional hydroxyl group

Question 2

Can sorbitol cross cell membranes?

Answer 2

NO, it is trapped in the cell and when it accumulates it produces osmotic stresses on cells by drawing water into the tissues

Question 3

What is the rxn that turns glucose into sorbitol?

Answer 3

Aldose reductase reduces (adds -OH) the glucose which produces sorbitol

Question 4

What is sorbitol dehydrogenase?

Answer 4

A second enzyme which oxidizes (takes off -OH and adds double bond to O) sorbitol to create fructose

Question 5

What cells have have sorbitol dehydrogenase?

Answer 5

The liver, overies, sperm and seminal vesicles (fluid that composes the semen)

Question 6

Why do the seminal vesicles have the 2 rxn pathway?

Answer 6

Its for the benefit of sperm, this is because sperm use fructose as a major energy source from carbs

Question 7

What are the consequences of sorbitol accumulation in diabetes?

Answer 7

Aldose reductase has a low affinity for glucose which means the polyol pathway is not active at normal blood glucose

During hyperglycemina (diabetes) glucose concentration in tissues like lens of eye, kidney, nerve cells increases - this leads conversion of glucose to sorbitol. These cells fail to convert sorbitol to fructose since they lack sorbitol dehydrogenase

Question 8

What does does sorbitol accumulation in the retina, kidney, nerve cells and lens of eye cause?

Answer 8

It leads to neuropathy, nephropathym retinopathy and cataracts in diabetic condition

Question 9

Where does galactose metabolized and what does it get turned into

Answer 9

Its metabolized in the liver and gets turned into glucose-6-phosphate

Question 10

How is galactose turned into glucose?

Answer 10

1. Galactokinase turns galactose to galactose-1P
2. G-1P is convetred to UDP-galactose *done by accepting UMP for a UDP-glucose using Galactose-1-P uridyl-transferase (GALT) enzyme
3. Epimerase converts the UDP-galactose to UDP-glucose

**UMP (uridyl monophosphate)

Question 11

What happens to the UDP-glucose formed from galactose?

Answer 11

It gets converted into glucose-6P which is an intermediate of glycolysis/gluconeogenesis and can be converted into glucose, ATP and pyruvate

Question 12

How does high levels of galactose in the blood lead to cataracts?

Answer 12

When galactose blood levels increase there is more synthesis of galactitol in the lens of the eye
This leads to inc of osmotic pressure in the lens, which leads to the cloudiness of the lens

**formation of galactitol in cataracts by galactitol is similar that that so sorbitol.
Aldose reductase converts galatose to galactitol just like it does glucose into sorbitol

Question 13

How is lactose produced in the mammary glands of females during lactation?

Answer 13

Lactose synthase catalyzes the transfer of galactose from UDP-galactose to glucose, which forms the disaccharide lactose

Question 14

What is the lactose synthase enzyme made up of?

Answer 14

Two protein subunits

1. catalytic galactosyltransferase subunit (in all tissues)
2. a regulatory subunit called a-lactalbumin (restricted to lactating mammary gland)

Question 15

What is the role of hormone prolactin?

Answer 15

It stimulates synthesis of the a-lactalbumin subunit in the mammary gland following child birth

Question 16

Can someone produce lactose in the human body if they do not have galactose in the diet?

Answer 16

Yes, we can use Uridine triphosphate (UTP) with glucose 1-P into UDP-glucose when we then convert to UDP-galactose when we can then turn into lactose

Question 17

What is purpose of glucuronide formation?

Answer 17

It increases the solubility of non-polar compounds (bilirubin, drugs, xenobiotics and other compounds containing a hydroxyl group) this allows them be excreted in bile or urine

Question 18

Where does glucouronide synthesis from glucose take place?

Answer 18

in the liver

Question 19

How are glucuronate residues turned into glucouronide?

Answer 19

In the liver the residues are transferred from UDP-glucuronate to the drug molecule to form glucuronide

*a glycosidic bond is then formed between the anomeric C of gucuronate and the OH of the non-polar compound (this increases its solubility making it easier to excrete)