Comparison of computer simulations of the F-type and L-type non-oxidative hexose monophosphate shunts with 31P-NMR experimental data from human erythrocytes

Authors


Correspondence to P. W. Kuchel. Department of Biochemistry, University of Sydney, Sydney, New South Wales 2006. Australia

Abstract

Mathematical modelling was used to predict the behaviour of the two most favoured schemes for the operation of the non-oxidative hexose monophosphate shunt (HMS), the F-type and the L-type pathways. The models simulate the time courses of sugar-phosphate concentrations when various substrates are metabolized via each pathway. A 31P-NMR technique, with which to observe time courses of concentrations of sugar phosphates in a human red cell lysate, was developed. The accuracy of each hypothesised scheme was then evaluated by comparing predicted with observed data.

The results were more consistent with time courses of sugar-phosphate levels predicted by the F-type (classical) pathway than those predicted by the L-type model. However, the accumulation of sedoheptulose 1,7-bisphosphate when a haemolysate was incubated with ribose 5-phosphated showed that the F-type pathway is not a complete description of the system of reactions. Transaldolase was demonstrated to be essential for the normal metabolism of sugar phosphates by haemolysates. The effects of the heat-inactivation of transldolase on the metabolism of sugar phosphates were accurately predicted by the F-type model.

The relevance of attempting to describe the reaction of the non-oxidative HMS as a distinct ‘pathway’ or ‘cycle’ is discussed.

Abbreviation
Ara5P

arabinose 5-phosphatec

CO

carbon monoxide

GrnP

dihydroxyacetone phosphate

Ery4P

erythrose 4-phosphate

Fru(1.6)P2

fructose 1,6-bisphosphate

Fru6P

fructose 6-phosphate

Gal1P

galactose 1-phosphate

Glc1P

glucose 1-phosphate

Glc(1.6)P2

glucose 1,6-bisphosphate

Glc6P

glucose 6-phosphate

GraP

glyceraldehyde 3-phosphate

GDH

glycerol-3-phosphate dehydrogenase

Hc

haematocrit

HMS

hexose monophosphate shunt

Man6P

mannose 6-phosphate

aOct(1,8)P2

altro-octulose 1.8-bisphosphate

iOct-(1,8)P2

ido-octulose 1,8-bisphosphate

Oct8P

octulose 8-phosphate

Rib5P

ribose 5-phosphate

Ru5P

ribulose 5-phosphate

Sed(1,7)P2

sedoheptulose 1,7-bisphosphate

Sed7P

sedoheptulose 7-phosphate

Et3P

triethyl phosphate

UDPGal

uridine (5′) diphosphogalactose

Xu5P

xylulose 5-phosphate. Prefixes α and β denote the respective anomers. suffixes p and f denote pyranose and furanose

Enzymes
 

Fructosebisphosphate aldolase (EC 4.1.2.13)

 

arabinose-5-phosphate isomerase (EC 5.3.1.13)

 

UDPglucose

 

galactose-1-phosphate uridyltransferase (EC 2.7.7.12)

 

glucose-6-phosphate dehydrogenase (EC 1.1.1.49)

 

glucose-6-phosphate isomerase (EC 5.3.1.9)

 

glycerol-3-phosphate dehydrogenase (EC 1.1.1.8)

 

mannose-6-phosphate isomerase (EC 5.3.1.8)

 

NADP glycohydrolase (EC 3.2.2.6)

 

phosphoglucomutase (EC 5.4.2.2.)

 

6-phosphogluconate dehydrogenase (EC 1.1.1.44)

 

6-phosphogluconolactonase (EC 3.1.1.31)

 

phosphotransferase (EC 2.7.1.–)

 

ribose-5-phosphate isomerase (EC 5.3.1.6)

 

ribulose-5-phosphate epimerase (EC 5.1.3.1)

 

transaldolase (EC 2.2.1.2)

 

transketolase (EC 2.2.1.1)

 

triosephosphate isomerase (EC 5.3.1.1)