SBS-713

Archaea, the third domain of life

Metabolism and Metabolic enzymes in

Archaea
Glycolysis and Gluconeogenesis

Dr. Mehwish Aslam

Last lecture
• ED Pathway
Catabolism of other sugars
• Haloarcula vallismortis and Halococcus saccharolyticus
• Fructose enters the EM pathway via ketohexokinase-catalyzed, ATP-dependent
phosphorylation to form fructose 1-phosphate
• Subsequent phosphorylation by 1-phosphofructokinase produces fructose 1,6-
bisphosphate.
• The presence of class I and II fructose-1,6-bisphosphate aldolases has been
documented in halophilic archaea
• Haloarcula vallismortis and H. mediterranei
• Catabolize sucrose and mannitol via this route after initial conversion to
fructose
• Sulfolobus species also have been shown to grow on sucrose as the sole carbon
and energy source
Catabolism of other sugars
• S. solfataricus
• Galactose, the C-4 epimer of glucose, is metabolized by the same
nonphosphorylative ED pathway enzymes that perform glucose
catabolism.
• P. furiosus
• First step of galactose catabolism appears to be phosphorylation at C-1,
and a specific galactokinase has been characterized
• Galactose is metabolized via the Leloir pathway, in which galactose 1-
phosphate is converted to glucose 1-phosphate by means of uridine
nucleotide intermediates.
Leloir pathway
Gluconeogenesis
• Occurs by a reversal of the chemical transformations of the classical EM
pathway
• Critical irreversible enzymatic steps of this pathway involve alternative
enzymes in archaeal gluconeogenesis
• the reactions catalyzed by pyruvate kinase and
• Phosphofructokinase/glucokianse
• Archaea use nonphosphorylating glyceraldehyde-3-phosphate
dehydrogenase or oxidoreductase in EM pathway
• But in gluconeogenesis it uses the traditional enzyme reactions of
phospho-glycerate kinase and glyceraldehyde-3-phosphate
dehydrogenase in the gluconeogenic direction.
Gluconeogenesis

• Phosphoenolpyruvate (PEP) synthase homologs are present in all sequenced

archaeal genomes and catalyze PEP formation from pyruvate, coupled with the
conversion of ATP to AMP + Pi.
• Several archaea have been found to contain a predicted gene for PEP car-
boxykinase; this enzyme has been characterized in Thermococcus kodakaraensis
Gluconeogenesis – Archaea

1 Phospho enolpyruvate synthase,

2 Enolase,
3 Phosphoglycerate mutase,
4 Phosphoglycerate kinase,
5 Glyceraldehyde-3-phosphate dehydrogenase,
6 Triose-phosphate isomerase,
7 Fructose-1,6- bisphosphate aldolase,
8 Fructose-1,6-bisphosphatase,
9 Phosphoglucose isomerase.
 Sugar nucleotide biosynthetic pathway
Xylose isomerase Mannoseisomerase

Glucokinase Fructokinase Mannokinase

Isomerase

Galactokinase Phosphoglucomutase Transaminase Phosphoglucomutase

Uridyltransferase Mutase Guanylyltransferase

Adenylyltransferase Guanylyltransferase
Epimerase N-acetyltransferase

Starch synthase Cellulose synthase Uridyltransferase

Uridyltransferase

Thymidylyltransferase Cytidylyltransferase
3-Phosphoglycerate Kinase and Triosephosphate Isomerase from
Hyperthermophilic Archaea
• The PGKs of eucaryal and bacterial sources represent monomeric enzymes
and exhibit a bilobal structure
• All bacterial and eucaryal triosephosphate isomerases are usually
homomeric dimers.
• A remarkable exception is represented by the bifunctional PGK/TIM fusion
protein in Thermotoga maritima, which forms a homomeric tetramer