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Glyoxylate, a new marker metabolite of type 2 diabetes.

Nikiforova VJ, Giesbertz P, Wiemer J, Bethan B, Looser R, Liebenberg V, Ruiz Noppinger P, Daniel H, Rein D - J Diabetes Res (2014)

Bottom Line: Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs).Reactive aldehydes derived from sugars play an important role in the generation of AGEs.Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

View Article: PubMed Central - PubMed

Affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow 127276, Russia.

ABSTRACT
Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

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Glyoxylate biochemical pathways for mammals. AGT: alanine-glyoxylate aminotransferase; AKR: aldo-keto reductase; ALDH: aldehyde dehydrogenase; DAAO: D-amino acid oxidase; FBPA: fructose-bisphosphate aldolase; GO: glycolate oxidase; GR: glyoxylate reductase; HOGA: 4-hydroxy-2-oxoglutarate aldolase; LDH: lactate dehydrogenase; PFK: phosphofructokinase.
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fig4: Glyoxylate biochemical pathways for mammals. AGT: alanine-glyoxylate aminotransferase; AKR: aldo-keto reductase; ALDH: aldehyde dehydrogenase; DAAO: D-amino acid oxidase; FBPA: fructose-bisphosphate aldolase; GO: glycolate oxidase; GR: glyoxylate reductase; HOGA: 4-hydroxy-2-oxoglutarate aldolase; LDH: lactate dehydrogenase; PFK: phosphofructokinase.

Mentions: Pathways that lead to the production of glyoxylate are similar in microorganisms, fungi, plants, and some invertebrates where the glyoxylate cycle is the prime source for the aldehyde during gluconeogenesis. In humans and higher organisms, glyoxylate is mainly a product of enzymatic glycolate oxidation in peroxisomes (Figure 4). This pathway is well-characterized as it is impaired in primary hyperoxaluria with abnormally increased production of oxalate for which glyoxylate is the major and direct precursor [25].


Glyoxylate, a new marker metabolite of type 2 diabetes.

Nikiforova VJ, Giesbertz P, Wiemer J, Bethan B, Looser R, Liebenberg V, Ruiz Noppinger P, Daniel H, Rein D - J Diabetes Res (2014)

Glyoxylate biochemical pathways for mammals. AGT: alanine-glyoxylate aminotransferase; AKR: aldo-keto reductase; ALDH: aldehyde dehydrogenase; DAAO: D-amino acid oxidase; FBPA: fructose-bisphosphate aldolase; GO: glycolate oxidase; GR: glyoxylate reductase; HOGA: 4-hydroxy-2-oxoglutarate aldolase; LDH: lactate dehydrogenase; PFK: phosphofructokinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4265698&req=5

fig4: Glyoxylate biochemical pathways for mammals. AGT: alanine-glyoxylate aminotransferase; AKR: aldo-keto reductase; ALDH: aldehyde dehydrogenase; DAAO: D-amino acid oxidase; FBPA: fructose-bisphosphate aldolase; GO: glycolate oxidase; GR: glyoxylate reductase; HOGA: 4-hydroxy-2-oxoglutarate aldolase; LDH: lactate dehydrogenase; PFK: phosphofructokinase.
Mentions: Pathways that lead to the production of glyoxylate are similar in microorganisms, fungi, plants, and some invertebrates where the glyoxylate cycle is the prime source for the aldehyde during gluconeogenesis. In humans and higher organisms, glyoxylate is mainly a product of enzymatic glycolate oxidation in peroxisomes (Figure 4). This pathway is well-characterized as it is impaired in primary hyperoxaluria with abnormally increased production of oxalate for which glyoxylate is the major and direct precursor [25].

Bottom Line: Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs).Reactive aldehydes derived from sugars play an important role in the generation of AGEs.Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

View Article: PubMed Central - PubMed

Affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow 127276, Russia.

ABSTRACT
Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

Show MeSH
Related in: MedlinePlus