S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate

Nathan L Alderson; Yuping Wang; Matthew Blatnik; Norma Frizzell; Michael D Walla; Timothy J Lyons; Nadja Alt; James A Carson; Ryoji Nagai; Suzanne R Thorpe; John W Baynes

doi:10.1016/j.abb.2006.03.005

S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate

Nathan L Alderson, Yuping Wang, Matthew Blatnik, Norma Frizzell, Michael D Walla, Timothy J Lyons, Nadja Alt, James A Carson, Ryoji Nagai, Suzanne R Thorpe, John W Baynes

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

111 Citations (Scopus)

Abstract

S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Archives of Biochemistry and Biophysics
Volume	450
Issue number	1
DOIs	https://doi.org/10.1016/j.abb.2006.03.005
Publication status	Published - 01 Jun 2006

Keywords

Animals
Anticarcinogenic Agents
Citric Acid Cycle
Collagen
Cysteine
Diabetes Mellitus, Experimental
Female
Fumarates
Glyceraldehyde-3-Phosphate Dehydrogenases
Glycosylation End Products, Advanced
Humans
Insulin
Insulin, Long-Acting
Insulin, Regular, Human
Muscle Proteins
Protein Processing, Post-Translational
Radiation-Protective Agents
Rats
Rats, Sprague-Dawley
Serum Albumin
Skin
Succinic Acid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.abb.2006.03.005

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title = "S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate",

abstract = "S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.",

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author = "Alderson, {Nathan L} and Yuping Wang and Matthew Blatnik and Norma Frizzell and Walla, {Michael D} and Lyons, {Timothy J} and Nadja Alt and Carson, {James A} and Ryoji Nagai and Thorpe, {Suzanne R} and Baynes, {John W}",

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doi = "10.1016/j.abb.2006.03.005",

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T2 - a novel chemical modification of tissue proteins by a Krebs cycle intermediate

AU - Alderson, Nathan L

AU - Wang, Yuping

AU - Blatnik, Matthew

AU - Frizzell, Norma

AU - Walla, Michael D

AU - Lyons, Timothy J

AU - Alt, Nadja

AU - Carson, James A

AU - Nagai, Ryoji

AU - Thorpe, Suzanne R

AU - Baynes, John W

PY - 2006/6/1

Y1 - 2006/6/1

N2 - S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

AB - S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

KW - Animals

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KW - Female

KW - Fumarates

KW - Glyceraldehyde-3-Phosphate Dehydrogenases

KW - Glycosylation End Products, Advanced

KW - Humans

KW - Insulin

KW - Insulin, Long-Acting

KW - Insulin, Regular, Human

KW - Muscle Proteins

KW - Protein Processing, Post-Translational

KW - Radiation-Protective Agents

KW - Rats

KW - Rats, Sprague-Dawley

KW - Serum Albumin

KW - Skin

KW - Succinic Acid

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DO - 10.1016/j.abb.2006.03.005

M3 - Article

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VL - 450

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EP - 8

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 1

ER -

S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate

Abstract

Keywords

UN SDGs

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