Control of Hepatic Utilization of Serine, Glycine and Threonine in Fed and Starved Rats

Rémésy, Christian; Fafournoux, Pierre; Demigné, Christian

doi:10.1093/jn/113.1.28

Cited by 57 publications

(38 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the only fate of D-glycerate in the liver appears to be its conversion to 2-P-glycerate by D-glycerate kinase, it is concluded that the marked deficiency of this enzyme found in the liver of the patient studied here is responsible for her metabolic disorder. Because D-glycerate is an intermediate in serine metabolism and that this amino acid is continuously taken up by the liver, at least in the rat [16], this interpretation accounts for the fact that the excretion of Dglycerate was continuous in this patient and that it increased following a serine load (Largilli&e, personal communication). These two characteristics were also found in the patient of Wadman et al [2], who, most likely, suffered from the same enzymatic defect.…”

Section: Enzymatic Defect In D-glyceric Aciduriamentioning

confidence: 90%

D‐Glycerate kinase deficiency as a cause of D‐glyceric aciduria

Schaftingen

1989

FEBS Letters

View full text Add to dashboard Cite

D-Glycerate kinase was measured in human livers thanks to a new, sensitive radiochemical assay. The enzyme was extremely unstable in extracts prepared in water, but was partly stabilized in a homogenization mixture containing inorganic phosphate, D-glycerate and EGTA. When extracted in such a stabilizing mixture, glycerate kinase activity amounted to 0.86 + 0.21 U/g in control rivers and to 0.03 U/g in the liver of a patient with D-glyceric aciduria. In contrast, Dglycerate dehydrogenase (glyoxylate reductase) and triokinase activities were not deficient in the liver of the same patient.It is concluded that D-glycerate kinase deficiency is a cause of D-glyceric aciduria.

show abstract

Section: Enzymatic Defect In D-glyceric Aciduriamentioning

confidence: 90%

D‐Glycerate kinase deficiency as a cause of D‐glyceric aciduria

Schaftingen

1989

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…In experiments with L-[1-14 C]serine, 14 CO 2 evolution can be ascribed to two routes: one further metabolism of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]glycine by GCS (14) and the other enzymatic or nonenzymatic decarboxylation of [1-14 C]hydroxypyruvate (28,29). In 24-h starved rats, hydroxypyruvate formation was hardly detectable unless Ͼ0.5 mM pyruvate was added, and the 14 CO 2 evolution was independent of the addition of pyruvate (Table I), probably because of the low levels of the pyruvate-dependent hydroxy-…”

Section: Relative Contributions Of Mitochondrial Shmt and Spt/ Agt Tomentioning

confidence: 99%

“…: (81)53-435-2322; Fax: (81)53-435-2323. 1 The abbreviations used are: SHMT, serine hydroxymethyltransferase (EC 2.1.2.1); mSHMT, mitochondrial isozyme of serine hydroxymethyltransferase; cSHMT, cytosolic isozyme of serine hydroxymethyltransferase; SDH, L-serine dehydratase (EC 4.2. serine, and indeed the results of experiments involving 14 Cserine (14) argued against this possibility.…”

mentioning

confidence: 99%

Flux of the l-Serine Metabolism in Rat Liver

Xue¹,

Fujie

Sakaguchi

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine: pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymethyltransferase is responsible for the interconversion between serine and glycine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of the serine-glycine pool. In vitro, flux through SDH was predominant in both 24-h starved and glucagontreated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution under quasi-physiological conditions (1 mM L-serine and 0.25 mM pyruvate) was about 1 ⁄10 of that through SDH. Flux through GCS accounted for only several percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3 H at the 3 position of L-serine is mostly removed in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway. The results showed that SPT/AGT contributed only 10-20% even after the enhancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.

show abstract

“…L-Serine is a nonessential amino acid but plays an important role in stabilizing the blood sugar concentration in the liver (16). It relates, furthermore, to many other substances, including sphingosine and the phosphatides, which are part of the myelin covering of the nerves, as well as the formation of activated C 1 units used for a number of anabolic processes (20).…”

mentioning

confidence: 99%

Reduced Folate Supply as a Key to Enhanced l -Serine Production by Corynebacterium glutamicum

Stolz

Peters‐Wendisch

Etterich

et al. 2007

Appl Environ Microbiol

View full text Add to dashboard Cite

The amino acid L-serine is required for pharmaceutical purposes, and the availability of a sugar-based microbial process for its production is desirable. However, a number of intracellular utilization routes prevent overproduction of L-serine, with the essential serine hydroxymethyltransferase (SHMT) (glyA) probably occupying a key position. We found that constructs of Corynebacterium glutamicum strains where chromosomal glyA expression is dependent on P tac and lacI Q are unstable, acquiring mutations in lacI Q , for instance. To overcome the inconvenient glyA expression control, we instead considered controlling SHMT activity by the availability of 5,6,7,8-tetrahydrofolate (THF). The pabAB and pabC genes of THF synthesis were identified and deleted in C. glutamicum, and the resulting strains were shown to require folate or 4-aminobenzoate for growth. Whereas the C. glutamicum ⌬sdaA strain (pserACB) accumulates only traces of L-serine, with the C. glutamicum ⌬pabABC⌬sdaA strain (pserACB), L-serine accumulation and growth responded in a dose-dependent manner to an external folate supply. At 0.1 mM folate, 81 mM L-serine accumulated. In a 20-liter controlled fed-batch culture, a 345 mM L-serine accumulation was achieved. Thus, an efficient and highly competitive process for microbial L-serine production is available.L-Serine is a nonessential amino acid but plays an important role in stabilizing the blood sugar concentration in the liver (16). It relates, furthermore, to many other substances, including sphingosine and the phosphatides, which are part of the myelin covering of the nerves, as well as the formation of activated C 1 units used for a number of anabolic processes (20). Therefore, L-serine is present in selected infusion solutions and also has other applications. For instance, it is an ingredient of skin lotions to ensure a proper hydration status. The total annual demand for L-serine is estimated to be 300 tons (5).The production processes currently used still rely on the extraction of L-serine from protein hydrolysates or from molasses, as well as on the enzymological conversion of glycine plus a C 1 compound, like methanol, to L-serine. The latter uses the reverse reaction of the serine hydroxymethyltransferase (SHMT) (6). Thus, an enzymatic system has been designed to convert glycine plus formaldehyde to L-serine (4). The cellular systems assayed employed, among other things, resting cells of methanol-utilizing bacteria, such as Hyphomicrobium methylovorum, where L-serine formation from glycine plus methanol was achieved (6). In such a system, up to 45 g liter Ϫ1 L-serine accumulation was possible, but only at a glycine yield of 50%, thus making the system less attractive. Also, alginate-entrapped cells of Corynebacterium glycinophilum were used for L-serine formation from glycine (21). It is self-evident that it would be most profitable to directly convert cheap sugar into L-serine. Although microbial processes for amino acid production are in general advancing quickly, attempts to develop L-serin...

show abstract

Control of Hepatic Utilization of Serine, Glycine and Threonine in Fed and Starved Rats

Cited by 57 publications

References 33 publications

D‐Glycerate kinase deficiency as a cause of D‐glyceric aciduria

D‐Glycerate kinase deficiency as a cause of D‐glyceric aciduria

Flux of the l-Serine Metabolism in Rat Liver

Reduced Folate Supply as a Key to Enhanced l -Serine Production by Corynebacterium glutamicum

Contact Info

Product

Resources

About