In Saccharomyces cerevisiae deletion of phosphoglucose isomerase can be suppressed by increased activities of enzymes of the hexose monophosphate pathway

Dickinson, J. Richard; Sobański, M.; Hewlins, M. J. E.

doi:10.1099/13500872-141-2-385

Cited by 17 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Branched-chain ␣-keto acid dehydrogenase has been purified from S. cerevisiae, and a number of its properties have been characterized (10). Our experience with 13 C nuclear magnetic resonance (NMR) spectroscopy for metabolic analysis in wild-type and mutant yeast (11)(12)(13)(14) led us to use this technique to determine the metabolic pathways used in fusel alcohol formation from branched-chain amino acids. This paper reports the catabolism of leucine to isoamyl alcohol.…”

mentioning

confidence: 99%

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

Dickinson

Lanterman

Danner

et al. 1997

Journal of Biological Chemistry

182

179

View full text Add to dashboard Cite

The metabolism of leucine to isoamyl alcohol in yeast was examined by 13 C nuclear magnetic resonance spectroscopy. The product of leucine transamination, ␣-ketoisocaproate had four potential routes to isoamyl alcohol. The first, via branched-chain ␣-keto acid dehydrogenase to isovaleryl-CoA with subsequent conversion to isovalerate by acyl-CoA hydrolase operates in wild-type cells where isovalerate appears to be an end product. This pathway is not required for the synthesis of isoamyl alcohol because abolition of branched-chain ␣-keto acid dehydrogenase activity in an lpd1 disruption mutant did not prevent the formation of isoamyl alcohol. A second possible route was via pyruvate decarboxylase; however, elimination of pyruvate decarboxylase activity in a pdc1 pdc5 pdc6 triple mutant did not decrease the levels of isoamyl alcohol produced. A third route utilizes ␣-ketoisocaproate reductase (a novel activity in Saccharomyces cerevisiae) but with no role in the formation of isoamyl alcohol from ␣-hydroxyisocaproate because cell homogenates could not convert ␣-hydroxyisocaproate to isoamyl alcohol. The final possibility was that a pyruvate decarboxylase-like enzyme encoded by YDL080c appears to be the major route of decarboxylation of ␣-ketoisocaproate to isoamyl alcohol although disruption of this gene reveals that at least one other unidentified decarboxylase can substitute to a minor extent.In most eukaryotes, the catabolism of the branched-chain amino acids leucine, isoleucine, and valine has been well understood for many years (1). The first step is a transamination in which ␣-ketoglutarate accepts the amino group (from leucine, isoleucine, and valine) producing glutamate and ␣-ketoisocaproic acid, ␣-keto-␤-methylvaleric acid and ␣-ketoisovaleric acid, respectively. Next is oxidative decarboxylation of the keto acids by branched-chain ␣-keto acid dehydrogenase to the corresponding acyl-CoA derivatives. Further steps yield, ultimately, acetyl-CoA and acetoacetate (from leucine), acetyl-CoA and propionyl-CoA (from isoleucine), and succinyl-CoA (from valine). All of these metabolites can enter the tricarboxylic acid (TCA) 1 cycle. It has been known for many years that yeasts do not operate the same metabolic routes because branched-chain amino acids can serve as the sole source of nitrogen but not carbon (2, 3). The predominant view, in a rather sparse literature, is that yeasts first use transamination but that decarboxylation of the keto acids proceeds via a "carboxylase" to an aldehyde that is then reduced in an NADH-linked reaction producing the appropriate "fusel" alcohol (2-4). This scheme is sometimes called the "Ehrlich pathway" to honor the originator of the ideas (5), which were slightly modified later (6). Acceptance of the so-called Ehrlich pathway is problematical for at least four reasons. First, the supposed pathway has never been proven to exist. Simply showing that e.g. radioactively labeled leucine is converted into isoamyl alcohol does not prove that the individual steps are those envisaged in ...

show abstract

mentioning

confidence: 99%

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

Dickinson

Lanterman

Danner

et al. 1997

Journal of Biological Chemistry

182

179

View full text Add to dashboard Cite

show abstract

“…For instance, in the case of methionine biosynthesis in Aspergillus nidulans, Paszewski and Grabski (1975) have shown that several dierent kinds of mutations will suppress the methionine requirement in mutants lacking either cystathionine c-synthase or b-cystathionase. Deletion of PGI1, encoding phosphoglucose isomerase in S. cerevisiae, can be suppressed by increased carbon¯ux through the hexose monophosphate pathway (Dickinson et al 1995). Furthermore, in Neurospora crassa, aro-1 mutants auxotrophic for aromatic compounds cannot convert dihydroxy shikimic acid (DHS) to shikimic acid (SA).…”

Section: Discussionmentioning

confidence: 99%

Locus-specific suppression of ilv1 in Saccharomyces cerevisiae by deregulation of CHA1 transcription

et al. 1997

View full text Add to dashboard Cite

The ILV1 gene of Saccharomyces cerevisiae encodes the anabolic threonine deaminase, which catalyzes the first committed step in isoleucine biosynthesis. Strains devoid of a functional Ilv1p have a requirement for isoleucine. Threonine can also be deaminated by a second serine/threonine deaminase encoded by the CHA1 gene. CHA1 is regulated by transcriptional induction by serine and threonine, and enables yeast to utilize the hydroxyamino acids as sole nitrogen source. Phenotypic suppression of ilv1 can occur by inducer-mediated transcriptional activation of the CHA1 gene. To identify mutations in putative trnas-acting factors regulating CHA1 expression, we have isolated and characterized three extragenic suppressors of ilv1. A dominant mutation, SIL4 (suppressor of ilv1), is allelic to HOM3. It increases the size of the threonine pool, by 15- to 20-fold, which is sufficient to induce CHA1 transcription, thereby creating a metabolic bypass of ilv1. A second dominant mutation, SIL3, and a recessive mutation, sil2, both suppress ilv1 by causing inducer-independent, constitutive transcription of CHA1. Importantly, sil2 and SIL3 increase the expression of a CHA1p-lacZ translational gene fusion, demonstrating that they exert their action through the CHA1 promoter. Genetic analysis showed that both SIL3 and sil2 are alleles of CHA4, a positive regulator of CHA1, i.e., they convert Cha4p to a constitutive activator.

show abstract

“…Carbohydrate metabolism in these species will be discussed in more detail later in this review (). The same strategy was used to assess the contribution of the PP pathway to glycolysis in S. cerevisiae [53].…”

Section: Reversibilitymentioning

confidence: 99%

“…In such a situation, cells are affected for growth on glucose, and it is assumed that this is because the PP pathway flux is too low to support growth. In S. cerevisiae [53], spontaneous revertants able to grow on glucose but still lacking the enzyme were obtained. By using [2‐ 13 C]glucose as substrate, it was shown that the activity of the PP pathway was significantly increased in the revertants.…”

Section: Metabolic Cyclesmentioning

confidence: 99%

Carbohydrate cycling in micro-organisms: what can¹³C-NMR tell us?

Portais

Delort

2002

FEMS Microbiol Rev

View full text Add to dashboard Cite

The extension of (13)C-nuclear magnetic resonance (NMR) techniques to study cellular metabolism over recent years has provided valuable data supporting the occurrence, diversity and extent of carbon cycling in the carbohydrate metabolism of micro-organisms. The occurrence of such cycles, resulting from the simultaneous operation of different and sometimes opposite individual steps, is inherently related to the network organisation of cellular metabolism. These cycles are tentatively classified here as 'reversibility', 'metabolic' and 'substrate' cycles on the basis of their balance in carbon and cofactors. Current hypotheses concerning the physiological relevance of carbohydrate cycles are discussed in light of the (13)C-NMR data. They most likely represent system-level mechanisms for coherent and timely partitioning of carbon resources to fit with the various biosynthetic, energetic or redox needs of cells and/or additional strategies in the adaptive capacity of micro-organisms to face variation in environmental conditions.

show abstract

In Saccharomyces cerevisiae deletion of phosphoglucose isomerase can be suppressed by increased activities of enzymes of the hexose monophosphate pathway

Cited by 17 publications

References 26 publications

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

Locus-specific suppression of ilv1 in Saccharomyces cerevisiae by deregulation of CHA1 transcription

Carbohydrate cycling in micro-organisms: what can¹³C-NMR tell us?

Contact Info

Product

Resources

About

In Saccharomyces cerevisiae deletion of phosphoglucose isomerase can be suppressed by increased activities of enzymes of the hexose monophosphate pathway

Cited by 17 publications

References 26 publications

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

A 13C Nuclear Magnetic Resonance Investigation of the Metabolism of Leucine to Isoamyl Alcohol in Saccharomyces cerevisiae

Locus-specific suppression of ilv1 in Saccharomyces cerevisiae by deregulation of CHA1 transcription

Carbohydrate cycling in micro-organisms: what can13C-NMR tell us?

Contact Info

Product

Resources

About

Carbohydrate cycling in micro-organisms: what can¹³C-NMR tell us?