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Propionic acidemia
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
When propionyl CoA accumulates, other metabolic products are found in the blood and urine. The predominant compound is 3-hydroxypropionic acid; others include tiglic acid, tiglyglycine, butanone, and propionylglycine. In addition, the unusual metabolite methylcitrate is formed by condensation of propionyl CoA and oxaloacetic acid [65]. This compound is an end product of metabolism and is very stable, resistant to conditions of shipment and bacterial contamination. In our hands, it is the most reliable chemical indicator of the presence of this disorder. It is useful in prenatal diagnosis, as well as the initial diagnosis. Odd chain fatty acids may accumulate in body lipids as a consequence of synthesis from propionyl CoA. They may be demonstrated and quantified in erythrocytes [66]. 3-Ureidopropionate is found in the urine [67], a consequence of propionate inhibition of ureidopropionase. The manifestations of patients with inherited deficiency of this enzyme of pyrimidine metabolism are reminiscent of those of propionic acidemic patients with changes in the basal ganglia, and there is in vitro evidence that ureidopropionate is neurotoxic [68]. 2-Methyl-3-oxovaleric acid, a product of self-condensation of two molecules of propionyl CoA, has been a useful metabolite for Lehnert and colleagues [14] for the diagnosis of propionic acidemia. Its reduction yields 3-hydroxy 2-methylvaleric acid. Hyperlysinemia or hyperlysinuria encountered in propionic acidemia [14] appears to reflect study during hyperammonemia, during which lysine accumulates.
Fungal Lipids
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
Among arachidonic acid synthesising strains of Mortierella spp. investigated by Shimizu et al.,57 a soil isolate, M. alpina 1S-4, produced 95% of the total mycelial fatty acids as odd-chain fatty acids, distributed in both neutral and polar lipid fractions, mainly 5,8,11,14-cis-nonadecatetraenoic acid. The biosynthesis of this was presumed to mimic that of arachidonic acid. On 5% N-heptadecane and 1% yeast extract as substrate, C19:4 accounted for up to 11.2% of total fatty acids of mycelial lipid (44.4 mg g-1 mycelial dry wt., a yield of 0.68 mg ml-1 culture broth). Decreased synthesis of C19:4 and accumulation of C19:3 resulted from the addition of sesamin, a specific inhibitor of Δ5-desaturation. Mortierella species incapable of C20 PUFA synthesis accumulated C17 fatty acids but not C19 PUFA when grown on odd-chain fatty substrates. The same team also demonstrated the production of a novel ω-l-eicosapentaenoic acid, cis-5,8,11,14,19-eicosapentaenoic acid (20:5, col), by M. alpina 1S-4 grown on a medium containing 4% 1-hexadecene.58 The fatty acid composition and unsaturation of Mortierella species has also been shown to be regulated by the carbon: nitrogen ratio in the culture medium; elevated carbon content (C:N = 40:1) results in cultures with increased proportions of saturated C12-C16 and monenoic C18 fatty acids and others with a higher content of polyenoic fatty acids in their triacylglycerols.59
Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Tatiana N. Yuzyuk, Heather A. Nelson, Lisa M. Johnson
Pancreatic dysfunction is not commonly seen in inborn errors of metabolism. Nevertheless, in addition to Pearson syndrome, methylmalonic acidemia (MMA; isolated) and propionic acidemia (PA) are two other inborn errors of metabolism characterized by pancreatic complications. MMA and PA are autosomal recessive disorders of propionate catabolism caused by the impaired function of mitochondrial enzymes, methylmalonyl-CoA mutase or propionyl-CoA carboxylase, respectively [75,76]. The enzymatic defects lead to a metabolic block in the final steps of the catabolic pathways of valine, isoleucine, methionine, threonine, cholesterol, and odd-chain fatty acids, resulting in the accumulation of specific metabolites (propionylcarnitine, methylcitric and 3-hydroxypropionic acids; methylmalonic acid specific to MMA). Most patients are identified by NBS and present in the neonatal period with vomiting, dehydration, weight loss, temperature instability, neurological involvement, irritability, and lethargy progressing to coma and seizures if left untreated. Mild and late-onset cases are also well documented [77,78].
Recent advances towards gene therapy for propionic acidemia: translation to the clinic
Published in Expert Review of Precision Medicine and Drug Development, 2019
Propionic acidemia (PA, MIM #606054) is an inborn error of metabolism affecting approximately 1 in 100,000 live births in the United States and up to 1 in 3,000 births in high-risk populations [1]. PA results from mutations in the alpha and beta subunits of the PCC enzyme are encoded by the nuclear PCCA and PCCB genes, respectively. Missense, nonsense, or splicing mutations can occur in either gene. Approximately 49% of all observed mutations are missense mutations that can produce hypomorphic proteins with reduced, but not completely ablated enzyme activity. Loss of PCC function leads to an inability to metabolize odd chain fatty acids and the amino acids valine, isoleucine, methionine, and threonine (Figure 1 and reviewed in [2]). The inability to metabolize these substrates produces elevations in a number of amino acids and metabolites. Elevations in propionyl carnitine (C3) in the blood is used as a primary newborn screen to detect PA. Certain newborn screening strategies use elevations in methyl citrate (MeCit) in the blood as a secondary confirmation of PA.
Circulating fatty acids as biomarkers of dairy fat intake: data from the lifelines biobank and cohort study
Published in Biomarkers, 2019
Ilse G. Pranger, Eva Corpeleijn, Frits A. J. Muskiet, Ido P. Kema, Cécile Singh-Povel, Stephan J. L. Bakker
Dairy fat consists of more than 400 different fatty acids (Mansson 2008). The fatty acids in dairy fat derive either directly from the animal’s diet, or indirectly from ruminal fermentation. The fatty acid composition of plasma, serum, erythrocytes and adipose tissue are known to partially reflect the fatty acid composition of the diet. Several fatty acids are to a large extent unique for dairy fat intake. They are present in measurable amounts in the circulation and tissue of humans (Smedman et al. 1999). Myristic acid (C14:0), pentadecanoic acid (C15:0), heptadecanoic acid (C17:0) and trans-palmitoleic acid (Trans-C16:1(n-7)) are commonly used dairy fat biomarkers (Wolk, et al.2001, Rosell et al. 2004, Biong et al.2006, Sun et al. 2007, Yakoob et al.2014, Warensjo et al. 2015, Lund-Blix et al. 2016, Yakoob et al. 2016 ). Particularly the odd-chain fatty acids C15:0 and C17:0 (Brevik et al.2005, Biong et al.2006, Sun et al.2007, Yakoob et al.2014, Warensjo et al.2015, Yakoob et al.2016, Lund-Blix et al. 2016), and the natural ruminant trans fat trans-C16:1(n-7) are often considered as fatty acids that mainly originate from dairy fat (Sun et al.2007, Yakoob et al. 2014, Yakoob et al.2016), because these fatty acids are synthesized by the bacterial flora in the rumen of the animal and cannot be synthesized in the human body (Jenkins et al. 2015). Correlations of C15:0, C17:0 and trans-C16:1(n-7) with dairy fat intake are variable. Papers that reported on the correlation between circulating dairy fat biomarkers in plasma and dairy fat intake showed correlations of 0.10–0.53 with C15:0 (Smedman et al. 1999, Wolk et al.2001, Rosell et al. 2004, Sun et al.2007, Yakoob et al.2014, Warensjo et al. 2015, Lund-Blix et al.2016, Yakoob et al.2016), of 0.16–0.36 with C17:0 (Wolk et al.2001, Rosell et al.2004, Sun et al.2007, Yakoob et al.2014, Warensjo et al.2015, Yakoob et al.2016), and of 0.13–0.30 with Trans-C16:1(n-7) (Sun et al.2007, Yakoob et al. 2014, Yakoob et al.2016). Despite the specific origin of these fatty acids, the correlations are relatively low and interest in other potential dairy fat biomarkers is therefore growing.