Specialization of the paralogue LYS21 determines lysine biosynthesis under respiratory metabolism in Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae, the first committed step of the lysine biosynthetic pathway is catalysed by two homocitrate synthases encoded by LYS20 and LYS21. We undertook a study of the duplicate homocitrate synthases to analyse whether their retention and presumable specialization have affected the efficiency of lysine biosynthesis in yeast. Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. Furthermore, results presented in this paper indicate that, in contrast to that which had been found for Lys20p, lysine is a strong allosteric inhibitor of Lys21p (K(i) 0.053 mM), which, in addition, induces positive co-operativity for alpha-ketoglutarate (alpha-KG) binding. Differential lysine inhibition and modulation by alpha-KG of the two isozymes, and the regulation of the intracellular amount of the two isoforms, give rise to an exquisite regulatory system, which balances the rate at which alpha-KG is diverted to lysine biosynthesis or to other metabolic pathways. It can thus be concluded that retention and further biochemical specialization of the LYS20- and LYS21-encoded enzymes with partially overlapping roles contributed to the acquisition of facultative metabolism.
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México DF 04510, México.
Héctor
H
Quezada
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México DF 04510, México.
Cristina
C
Aranda
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México DF 04510, México.
Alexander
A
DeLuna
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México DF 04510, México.
Hugo
H
Hernández
Laboratorio de Fisicoquímica e Ingeniería de Proteínas, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF 04510, México.
Mario L
ML
Calcagno
Instituto Nacional de Cardiología, Departamento de Bioquímica, Tlalpan, México DF, México.
Álvaro
Á
Marín-Hernández
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México DF 04510, México.
Alicia
A
González
D019069:Cell Respiration / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008239:Lysine / Q000096:biosynthesis* / Q000494:pharmacology; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
D007527:Isoenzymes; D007656:Ketoglutaric Acids; D029701:Saccharomyces cerevisiae Proteins; C021365:homocitrate synthase; D007652:Oxo-Acid-Lyases; D008239:Lysine