Uronic Acid Pathway For medical students

CHARLES A. CABATAÑA, M.D., BSN, RN, FPAMS

Medical Specialist II

Cebu City Medical Center

Essential Features and Functional

Significance

1.An alternative pathway for the oxidation

of glucose. Like the PPP, it does not lead to

the generation of ATP. It is a source of

activated glucuronate (UDP glucuronate)

required for:

a. Synthesis of glycosaminoglycans

(e.g. chondroitin SO4) of connective

tissues.

Uronic Acid Pathway

Essential Features and Functional

Significance

b. Formation of glucuronides where

certain substrates such as steroid

hormones, drugs and bilirubin are

conjugated for excretion in urine or

bile.

c. Synthesis of certain polysaccharides

(glycogen).

Uronic Acid Pathway

Essential Features and Functional

Significance

2. Source of ascorbic acid in most animals

except in humans, primates and guinea

pigs.

3. Needed for formation of pentose and the

metabolism of non-phosphorylated sugar

derivatives.

Uronic Acid Pathway

1. Isomerization of Glucose 6-PO4 to

Glucose 1-PO4 by phosphoglucomutase.

Uronic Acid Reaction Pathway

2. Formation of UDP Glucose from G1-PO4

and UTP by UDPG phosphorylase.

Uronic Acid Reaction Pathway

3. Oxidation of UDP

Glucose (at carbon

6) to UDP

Glucuronate by a

NAD dependent

UDP Glucose

dehydrogenase.

UDP glucuronate

is the “active” form

of glucuronate

used for synthetic

reactions.

Uronic Acid Reaction Pathway

4. Conversion of UDP glucuronate to free

D-glucuronate by hydrolase.

Uronic Acid Reaction Pathway

5. Reduction of D-glucuronate to L-gulonate

by a NADPH-dependent L-gulonate DH.

Uronic Acid Reaction Pathway

NADPH + H NADP

6. Formation of ascobic acid from L-gulonate.

a. L-gulonate is initially dehydrated by

aldonolactonase to L-gulonolactone.

Uronic Acid Reaction Pathway

H2O

b. L-gulonolactone is oxidized

to 2-keto L-gulonolactone

by gulonolactone oxidase.

This step is blocked in

humans, primates and

guinea pig.

Among humans, ascorbic

acid has to be supplied in

the diet otherwise Vitamin

C deficiency will develop in

the form of scurvy.

Uronic Acid Reaction Pathway

b. L-gulonolactone is oxidized

to 2-keto L-gulonolactone

by gulonolactone oxidase.

This step is blocked in

humans, primates and

guinea pig.

Among humans, ascorbic

acid has to be supplied in

the diet otherwise Vitamin

C deficiency will develop in

the form of scurvy.

Uronic Acid Reaction Pathway

c. 2 Keto L-gulonolactone

is spontaneously

converted to L-

ascorbic acid.

Uronic Acid Reaction Pathway

7. Oxidation of L-gulonate into 3 keto L-

gulonate by a NAD-dependent keto L-

gulonate DH.

Uronic Acid Reaction Pathway

NAD NADH + H

8. Decarboxylation of 3 keto L-gulonate to L-

xylulose

Uronic Acid Reaction Pathway

9. Conversion of L-xylulose to D-xylulose

a. Reduction of L-xylulose to xylitol by

NADPH-dependent L-xylulose DH.

Uronic Acid Reaction Pathway

9. Conversion of L-xylulose to D-xylulose

b. Oxidation of Xylitol to D-xylulose by NAD-

dependent Xylulose DH

Uronic Acid Reaction Pathway

10. Phosphorylation

of D-xylulose to

D-xylulose 5-PO4

using ATP by

xylulokinase. D-

xylulose 5-PO4

can then be

metabolized via

the PPP.

Uronic Acid Reaction Pathway

Metabolism of D-xylulose 5-PO4 Via the PPP

Essential Pentosuria

Excretion of large quantities of L-xylulose

in the urine due to genetic absence of L-

xylulose DH.

Clinical Conditions Involving the

Uronic Acid Pathway

Essential Pentosuria

Does not appear to involve any serious

physiologic consequences, however the urine

must be checked for the presence of L-

xylulose.

Clinical Conditions Involving the

Uronic Acid Pathway

Clinical Conditions Involving the

Uronic Acid Pathway

Oxalosis

Calcium oxalate deposition in

the brain and kidneys.

May result from parenteral

administration of xylitol which

is converted to oxalate.

Xylitol in found in carrots,

plums, spinach and in

sweeteners of chewing gum.