THE EXCRETION OF C₆–C₁₀‐DICARBOXYLIC ACIDS IN THE URINE OF NEWBORN INFANTS DURING STARVATION

Abstract

The excretion of C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, was measured during the three first days of life in 3 fasting newborns, 2 newborns fed with isocaloric glucose and 2 newborns given mothers'-milk. On the second and third day of life the starved children excreted 27-84 mmol adipic acid/mol creatinine, 6-22 mmol suberic acid/mol creatinine and 4-7 mmol sebacic acid/mol creatinine. The excretion of C6-C10-dicarboxylic acids in the neonates given glucose or mothers'-milk was, for the first three days of life, 0-9 mmol adipic acid/mol creatinine, 0-10 mmol suberic acid/mol creatinine and 0-4 mmol sebacic acid/mol creatinine. The latter amounts are equivalent to the excretion of dicarboxylic acids in older children. It is argued that the detected dicarboxylic acids are formed by omega-oxidation of long-chain monocarboxylic acids followed by beta-oxidation, and that the excreted amounts reflect omega-oxidation activity. It is speculated that the substantial omega-oxidation activity in the starving newborn serve to provide succinyl-CoA-substrate for the citric acid cycle and for gluconeogenesis.

The biological significance of ω-oxidation of fatty acids

“…36 ) Moreover, they demonstrated that the administration of dicarboxylic acids to starved rats decreased the concentration of ketone bodies in the blood. 36 ) Gregersen et al 37 ) observed that the substantial ω-oxidation activity of fatty acids in starving newborn infants served to provide succinyl-CoA-substrate for the citric acid cycle and as well as for gluconeogenesis. Mortensen 38 ) demonstrated that the ω-oxidation of fatty acids might have importance metabolic influence in situations where the living organisms lacked carbohydrates and largely have to utilize fats for energy demand.…”

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

“…73 In addition, increased ω-oxidation may provide succinyl-CoA for the Krebs cycle and gluconeogenesis. 73,74 Ω-oxidation is also upregulated with increased cytochrome P450 enzyme activity. 75 C4-DCA modifies (succinylates) several mitochondrial proteins, 76 while other DCAs such as azelaic acid (C9-DCA) may have anti-inflammatory, antioxidative, and bactericidal activity.…”

“…There is evidence of oxidative damage to proteins and lipids in AD, 71 and we anticipate effects from ω‐oxidation will be manifest in AD. Ω‐oxidation of lipids resulting in short‐ and medium‐chain dicarboxylic acid (DCA) production is normally a minor pathway for normal fatty acid metabolism 72 ; it is considered a rescue pathway that compensates for defects in FAO, and urinary excretion of DCAs increase in persons who have defects in fatty acid metabolism 73 . In addition, increased ω‐oxidation may provide succinyl‐CoA for the Krebs cycle and gluconeogenesis 73,74 .…”

“…Ω‐oxidation of lipids resulting in short‐ and medium‐chain dicarboxylic acid (DCA) production is normally a minor pathway for normal fatty acid metabolism 72 ; it is considered a rescue pathway that compensates for defects in FAO, and urinary excretion of DCAs increase in persons who have defects in fatty acid metabolism 73 . In addition, increased ω‐oxidation may provide succinyl‐CoA for the Krebs cycle and gluconeogenesis 73,74 . Ω‐oxidation is also upregulated with increased cytochrome P450 enzyme activity 75 .…”

Plasma metabolomics indicates metabolic perturbations in low birth weight piglets supplemented with arginine1

“…Elevations in the long-chain dicarboxylic acids (e.g., octadecanedioate and hexadecanedioate) in LBW-Ala piglets, as compared with ABW-Ala piglets, suggest that omega oxidation of FFA may be occurring in the endoplasmic reticulum. Omega oxidation is considered a minor pathway for fatty acid catabolism but has been previously shown to compensate for deficiencies in the β-oxidation pathway in human infants (Gregersen and Ingerslev, 1979). This alternative pathway may provide succinyl-CoA (i.e., the end product of omega oxidation) to be used in the TCA cycle for energy production.…”