Vitamin B(12) (cobalamin, Cbl) is essential to the function of two human enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). The conversion of dietary Cbl to its cofactor forms, methyl-Cbl (MeCbl) for MS and adenosyl-Cbl (AdoCbl) for MUT, located in the cytosol and mitochondria, respectively, requires a complex pathway of intracellular processing and trafficking. One of the processing proteins, MMAA (methylmalonic aciduria type A), is implicated in the mitochondrial assembly of AdoCbl into MUT and is defective in children from the cblA complementation group of cobalamin disorders. To characterize the functional interplay between MMAA and MUT, we have crystallized human MMAA in the GDP-bound form and human MUT in the apo, holo, and substrate-bound ternary forms. Structures of both proteins reveal highly conserved domain architecture and catalytic machinery for ligand binding, yet they show substantially different dimeric assembly and interaction, compared with their bacterial

In any vitamin B12 deficiency there is an increase in levels of methylmalonic acid, which is the main characteristic of B12 deficiency, which differentiates it from folic acid deficiency. Vegetarians should analyze what levels of methylmalonic acid present to determine possible subclinical B12 deficits.. The increase in methylmalonic acid is due to the lack of activity of the methylmalonyl-CoA mutase enzyme, which requires cobalamin (vitamin B12) as the coenzyme to produce Succinyl-CoA (which will subsequently be used to form erythrocytes).. Therefore, methylmalonic acid accumulates because Succinyl-CoA can not be formed, because of the decreased activity of the enzyme methylmalonyl-CoA mutase, which uses B12 as cofactor. This leads to decreased synthesis of the heme group (no red blood cells can be formed) and decreased gluconeogenesis.. The explanatory scheme of the reaction is as follows:. ...

Methylmalonic acidemia (MMA) is an autosomal recessive disorder resulting in failure to process various amino acids and lipids. The classical form results in methylmalonyl CoA mutase deficiency, preventing the Vit B12-dependent conversion of methylmalonyl CoA to succinyl CoA, required in Krebs cycle. Patients typically present in early infancy with lethargy, vomiting, dehydration and failure to thrive. Long-term complications include renal failure (CRF), encephalopathy and pancreatitis. 4 cases of optic atrophy (OA) have been reported in classical MMA on appropriate dietary restrictions. The exact etiology is unknown but likely is multi-factorial. With improved survival of patients offered advanced treatment, OA needs to be identified so that prophylactic/therapeutic intervention, when available, can be incorporated into management protocols. The purpose of this observational study is to identify and determine the prevalence of OA in a small cohort of patients with classical MMA.. ...

Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We biochemically investigated how missense mutations in MMAA in 22 patients lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by ...

Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We biochemically investigated how missense mutations in MMAA in 22 patients lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing

Methylmalonic Acidemia (MMA) is a metabolic disorder affecting 1 in 25,000 to 48,000 individuals globally. MMA is characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. About 60% of MMA cases stem from mutations in the methylmalonyl CoA mutase (MUT) gene encoding a key enzyme required to break down amino acids and lipids. Previous efforts to develop mice with null mutations in MUT have been unsuccessful, as such mutations result in neonatal death ...

Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: ...

Vitamin B12 (cobalamin, Cbl) is required for cellular metabolism. It is an essential coenzyme in mammals for two reactions: the conversion of homocysteine to methionine by the enzyme methionine synthase and the conversion of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase. Symptoms of Cbl deficiency are hematological, neurological and cognitive, including megaloblastic anaemia, tingling and numbness of the extremities, gait abnormalities, visual disturbances, memory loss and dementia. During pregnancy Cbl is essential, presumably because of its role in DNA synthesis and methionine synthesis; however, there are conflicting studies regarding an association between early pregnancy loss and Cbl deficiency. We here review the literature about the requirement for Cbl during pregnancy, and summarized what is known of the expression pattern and function of genes required for Cbl metabolism in embryonic mouse models.

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A metabolic pathway is a series of chemical conversions, in which an enzyme catalyzes each reaction. Enzymes are the products of genes, and an alteration of a gene from its normal form may produce an enzyme that does not function properly. The compound propionyl coenzyme A is the thioester of propionic acid conjugated with coenzyme A (CoA), a thiol. When propionyl coenzyme A is produced in the body, it is converted into succinyl coenzyme A in a pathway that is three steps long: Propionyl CoA carboxylase is the enzyme that changes propionyl CoA into D-methylmalonyl CoA, and this compound is converted into L-methylmalonyl CoA by methylmalonyl CoA epimerase. Finally, this compound is converted into succinyl CoA by the vitamin B12-dependent enzyme methylmalonyl CoA mutase. The gene for this last enzyme is defective in methylmalonic academia, and the inheritance pattern is autosomal recessive. When this happens, the previous compounds build up in concentration. At some point the bond linking ...

A reverse-phase h.p.l.c. system for the resolution of the acyl-CoA intermediates of the degradation of 3-methyl-2-oxopentanoate is described. The validation of a method for the measurement of radioactive intermediates produced by the incubation of [U-14C]3-methyl-2-oxopentanoate with rat liver mitochondrial fractions is described. The absence of bicarbonate caused the accumulation of [14C]propionyl-CoA. The accumulation of [14C]2-methylbutyryl-CoA was observed in incubations with mitochondrial fractions derived from riboflavin-deficient animals. Studies of the accumulation of labelled intermediates with time suggest that there is regulation of the pathway of isoleucine degradation at methylmalonyl-CoA mutase, as suggested for valine [Corkey, Martin-Requero, Walajtys-Rode, Williams & Williamson (1982) J. Biol. Chem. 257, 9668-9676]. These studies demonstrate that h.p.l.c. with on-line continuous radiochemical detection is a powerful method for the investigation of the control of intermediary ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the mitochondrial enzyme methylmalonyl Coenzyme A mutase. In humans, the product of this gene is a vitamin B12-dependent enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, while in other species this enzyme may have different functions. Mutations in this gene may lead to various types of methylmalonic aciduria. [provided by RefSeq, Jul 2008 ...

Vitamin B12 is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin-dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited during catalysis by the isomerases and the methyltransferases. Thus, the cobalt-carbon bond ruptures homolytically in the isomerases, whereas it is cleaved heterolytically in the methyltransferases. The reaction mechanism of the dehalogenases, the most recently discovered class of B12 enzymes, is poorly understood. Over the past decade our understanding of the reaction mechanisms of B12 enzymes has been greatly enhanced by the availability of large amounts of enzyme that have afforded detailed structure-function studies, and these recent advances are the subject of this review.

Mouse polyclonal Methylmalonyl Coenzyme A mutase antibody validated for WB, IHC, ICC/IF and tested in Human and Rat. Referenced in 2 publications and 1…

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TY - JOUR. T1 - Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism. AU - Anzmann, Arianna Franca. AU - Pinto, Sneha. AU - Busa, Veronica. AU - Carlson, James. AU - McRitchie, Susan. AU - Sumner, Susan. AU - Pandey, Akhilesh. AU - Vernon, Hilary J.. N1 - Funding Information: National Institutes of Health , Grant K08 HD073492-01 and the Propionic Acidemia Foundation. Publisher Copyright: © 2019 Elsevier B.V.. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Background: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are related disorders of mitochondrial propionate metabolism, caused by defects in methylmalonyl-CoA mutase (MUT) and propionyl-CoA carboxylase (PCC), respectively. These biochemical defects lead to a complex cascade of downstream metabolic abnormalities, and identification of these abnormal pathways has important implications for understanding disease pathophysiology. Using a multi-omics approach in cellular ...

Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessive metabolic disorder. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood. Methylmalonic acidemia stems from several genotypes, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries. Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening. Stroke Progressive encephalopathy Seizure Kidney failure ...

The ABCD4 gene provides instructions for making a protein that is involved in the conversion of vitamin B12 (also known as cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fats (lipids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.. The ABCD4 protein is found in the membrane that surrounds cell structures called lysosomes. Lysosomes are compartments within cells in which enzymes digest and recycle materials. In the lysosomal membrane, the ABCD4 protein interacts with another protein called LMBD1 ...

Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Rarely, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered intracellular metabolism of vitamin B12 produces another group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class cobalamin C (cblC), D and F and ...

Methylmalonic acidemia (MMA) is a heterogeneous disorder of propionate metabolism. MMA is caused by deficiency of the mitochondrial enzyme, methylmalonyl-CoA mutase-apoenzyme activity (MUT) or defective in adenosylcobalamin (coenzyme) synthesis.1 The most patients with cblA and half patients with cblB forms of MMA are responsive to vitamin B12.2,3 Clinical manifestation of MMA may be acute or chronic. The acute form of the disease occurs during infancy and even as early as the second day of life with poor feeding, vomiting, dehydration, weight loss, temperature instability, lethargy, hypotonia, seizure and progressing to coma. Laboratory findings include: metabolic acidosis, ketosis, hypoglycemia, hyperlactatemia, hyperammonemia, pancytopenia.4. Definitive diagnosis of isolated MMA is based on analysis of organic acids in plasma and/or urine; however genetic testing diagnosis in some condition is accessible to confirm the diagnosis of isolated MMA. Below, we describe the presentation and ...

Oberholzer et al and Stokke et al reported the first patients with methylmalonic acidemia (MMA). Clinical and genetic heterogeneity became evident very early when some patients responded to pharmacological doses of cobalamin (vitamin B-12) and others did not.

Chronic kidney disease (CKD) is one of the main long-term prognosis factors in methylmalonic acidemia (MMA), a rare disease of propionate catabolism. Our objective was to precisely address the clinical and biological characteristics of long-term CKD in MMA adolescent and adult patients. In this retrospective study, we included MMA patients older than 13 years who had not received kidney and/or liver transplantation. We explored tubular functions, with special attention to proximal tubular function. We measured glomerular filtration rate (mGFR) by iohexol clearance and compared it to estimated glomerular filtration rate (eGFR) by Schwartz formula and CKD-EPI. Thirteen patients were included (M/F = 5/8). Median age was 24 years (13 to 32). Median mGFR was 57 mL/min/1.73 m2 (23.3 to 105 mL/min/1.73 m2). Ten out of 13 patients had mGFR below 90 mL/min/1.73 m2. No patient had significant glomerular proteinuria. No patient had complete Fanconi syndrome. Only one patient had biological signs suggestive of

See Solace Nutritions medical food to help in the dietary management of methylmalonic acidemia. VB12MAX is a hydroxocobalamin (vitamin B12) liquid concentrate.

A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Methylmalonic acidemia

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA and cardiomyopathy mainly in PA. Except for vitamin B12 responsive forms of MMA the outcome remains poor despite the existence of apparently effective therapy with a low protein diet and carnitine. This may be related to under recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of

The cblD defect of intracellular vitamin B(12) metabolism can lead to isolated methylmalonic aciduria (cblD-MMA) or homocystinuria (cblD-HC), or combined methylmalonic aciduria and homocystinuria (cblD-MMA/HC). We studied the mechanism whereby MMADHC mutations can lead to three phenotypes. The effect of various expression vectors containing MMADHC modified to contain an enhanced mitochondrial leader sequence or mutations changing possible downstream sites of reinitiation of translation or mutations introducing stop codons on rescue of adenosyl- and methylcobalamin (MeCbl) formation was studied. The constructs were transfected into cell lines derived from various cblD patients fibroblasts. Expression of 10 mutant alleles from 15 cblD patients confirmed that the nature and location of the mutations correlate with the biochemical phenotype. In cblD-MMA/HC cells, improving mitochondrial targeting of MMADHC clearly increased the formation of adenosylcobalamin (AdoCbl) with a concomitant decrease in ...

Obviously its all quite restrictive and thats a problem for school trips and things. Youve got to notify local hospitals in advance and normally get GOSH to fax my regimes and things through so I can get treatment quickly if needed. I cant go on school trips abroad - it would be too difficult for the school.. Also, I take packed lunches to school, and when we go to restaurants, Mum has to phone ahead to explain. When we go on holiday, we have to take a load of food with us, so I cant stay in a hotel. It does restrict the type of holiday we go on.. My family cope really well. They couldnt do anything better to adapt, theyre incredible. But MMA really isnt as bad as you might read on the internet.. Ive been to the British Grand Prix. Id always said to Mum and Dad that I really wanted to see a Formula 1™ race, and when we came to GOSH someone showed us a poster. We filled out an application form and I got selected. I was over the moon. We went on a garage tour and I met drivers ...

Adenosylcobalamin Decreased Symptom Checker: Possible causes include Methylmalonic Acidemia with Homocystinuria Type cblJ. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.

abbr.: PCCase; EC 6.4.1.3; an enzyme that catalyses a reaction between ATP, propanoyl‐CoA, and HCO3− to form (S)‐methylmalonyl‐CoA, ADP, and orthophosphate; biotin is a coenzyme. It is an enzyme in ... ...

Among the defects in cobalamin metabolism, two complimentary groups, Cbl A and B, affect synthesis of adenosyl cobalamin. Two other groups, Cbl E and G, affect the synthesis of methyl cobalamin, which is an essential cofactor for methionine synthase, and defects result in hyperhomocysteinemia. Also, defects in Cbl C, D, and F affect synthesis of both adenosyl cobalamin and methyl cobalamin, and will therefore result in both methylmalonic acidemia and hyperhomocysteinemia ...

Propionyl-CoA metabolism: propionyl-CoA is an intermediate in the catabolism of a number of amino acids, as well as in the breakdown of odd-chain fatty acids. Propionyl-CoA (3-C) enters the TCA Cycle at succinyl-CoA (4-C), thus another carbon must be added to bring it into mainstream metabolism. A biotin-dependent carboxylase adds carbon dioxide at the cost of one ATP to give D-methylmalonyl-CoA. D-methylmalonyl-CoA is then racemized to L-methylmalonyl-CoA. Methylmalonyl-CoA is a branched-chain, whereas succinyl-CoA is straight-chain: the carboxyl group and a hydrogen must be exchanged. This exchange requires C-C bond-breaking and making, a process apparently involving a Co-C bond intermediate. The cobalamin cofactor derived from Vit B12 is used in catalyzing this reaction. ...

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with ...

A recent case report by Traber et al in the Journal of Neuroopthalmology (August 25, 2011 Epub) describes an adult patient with methylmalonic acidemia (MMA) and sudden onset of bilateral vision loss with optic atrophy. This may not be commonly though of as a frequent adult complication of MMA. However, this sudden onset of vision loss has been described before in adults […]. ...

RAS-like GTPase Transport Protein: This protein from M. tuberculosis is a member of the Ras super family of proteins. Ras is involved in signal transduction and activating mutations in human Ras are associated with many types of cancer. While originally annotated as an arginine/ornithine transport system ATPase, we show that the protein is most likely a GTPase based on the compound (GDP) bound to the structure. The structure of the GTPase domain of the protein is similar to that of human Ras and several amino acids that line the GTP binding pocket are conserved. Ras-like GTPases use the organic chemical GTP (guanosine-5-triphosphate) as a regulator of function. During the signal transduction reaction, GTP is converted to GDP (guanosine diphosphate). GDP is shown in the figure bound to the active site of the M. tuberculosisRAS-like GTPase crystal structure. Our structure is related in sequence and structure to the methylmalonic acidemia type A protein (PDB ID 2WWW), a protein which is responsible for a

Complete information for MMAA gene (Protein Coding), Methylmalonic Aciduria (Cobalamin Deficiency) CblA Type, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Eicosanoyl-CoA + 4 Methylmalonyl-CoA + 8 NADPH + 8 H+ + Acyl-carrier protein ,=, C32-Mycocerosyl-[acp] + 5 CoA + 4 CO2 + 8 NADP+ + 4 ...

At its June 4, 2021, meeting, the ICMA Executive Board voted to approve the following ethics recommendations from the ICMA Committee on Professional Conduct (CPC) after a thorough review process:

Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.

The Content of this eMagazine has been contributed by members of ICMA for the exclusive use of other ICMA members for their educational and professional development. The ICMA hosts this magazine as a creative marketplace bringing together content provider members who upload interesting articles they have come across that they believe that other management accounting professionals would like to peruse for their educational and professional development. As a creative marketplace On Target is protected by the Digital Millennium Copyright Act. Although ICMA constantly monitors the uploads for copyright violations; if an article or image has been uploaded by a member without obtaining the required authority, please contact ICMA on www.cmawebline.org, and the material will be taken down immediately.. ...

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Unknown functionEnzymes of unknown specificityPPOX class probable F420-dependent enzyme, Rv3369 family (TIGR03667; EC 1.-.-.-; HMM-score: 18.3) ...

TY - JOUR. T1 - Early-onset combined methylmalonic aciduria and homocystinuria. T2 - Neuroradiologic findings. AU - Rossi, A.. AU - Cerone, R.. AU - Biancheri, R.. AU - Gatti, R.. AU - Schiaffino, M. C.. AU - Fonda, C.. AU - Zammarchi, E.. AU - Tortori-Donati, P.. PY - 2001. Y1 - 2001. N2 - BACKGROUND AND PURPOSE: Combined methylmalonic aciduria and homocystinuria (MMA-HC) is caused by impaired hepatic conversion of dietary cobalamin to methylcobalamin and adenosylcobalamin, resulting in decreased activity of methylmalonyl-CoA mutase and methionine synthase. Patients with the early-onset variety present within 12 months of age with severe neurologic, hematologic, and gastrointestinal abnormalities. We describe the neuroradiologic features of early-onset MMA-HC and discuss related pathophysiological mechanisms. METHODS: Twelve infants with hypotonia, failure to thrive, poor feeding, and hematologic abnormalities were diagnosed with MMA-HC on the basis of a typical plasmatic and urinary metabolic ...

Accepted name: methylmalonyl-CoA decarboxylase. Reaction: (S)-methylmalonyl-CoA = propanoyl-CoA + CO2. Other name(s): propionyl-CoA carboxylase (incorrect); propionyl coenzyme A carboxylase (incorrect); methylmalonyl-coenzyme A decarboxylase; (S)-2-methyl-3-oxopropanoyl-CoA carboxy-lyase (incorrect); (S)-methylmalonyl-CoA carboxy-lyase. Systematic name: (S)-methylmalonyl-CoA carboxy-lyase (propanoyl-CoA-forming). Comments: The enzyme from Veillonella alcalescens is a biotinyl-protein, requires Na+ and acts as a sodium pump.. Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37289-44-4. References:. 1. Galivan, J.H. and Allen, S.H.G. Methylmalonyl coenzyme A decarboxylase. Its role in succinate decarboxylation by Micrococcus lactilyticus. J. Biol. Chem. 243 (1968) 1253-1261. [PMID: 5646172]. 2. Hilpert, W. and Dimroth, P. Conversion of the chemical energy of methylmalonyl-CoA decarboxylation into a Na+ gradient. Nature 296 (1982) 584-585. [PMID: 7070502]. 3. ...

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100-000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA and cardiomyopathy mainly in PA. Except for vitamin B12 responsive forms of MMA the outcome remains poor despite the existence of apparently effective therapy with a low protein diet and carnitine. This may be related to under recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of

A malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. [PubChem]

Methods/Design This 5-year, Phase II, double-blind study aims to recruit and enroll 34 PA and MMA patients during acute episodes of hyperammonemia.. The primary aim is to circumvent the long-term neurodevelopmental decline due to having a prolonged levels of ammonia during crisis in the blood and urine. After treatment and crisis resolution with Carbaglu or placebo and standard of care therapy, measures of neurodevelopmental outcomes (Bayley II and Functional Status Scale) are being measured at 9, 15,21 and 30 months post-discharge from the hospital. Safety of NCG treatment will also be monitored as measured by close examination of adverse events and laboratory blood tests. To test for the effectiveness of NCG, longitudinal models to evaluate the groupwise difference (NCG vs. Placebo) in the trajectory of change in neurodevelopmental outcomes and safety analyses between drug and placebo patients.. Subsequent Episodes At any time after the initial episode, participants may present to the hospital ...

The kinetics of the thermolysis of 5-deoxyadenosylcobalamin (AdoCbl, coenzyme B12) in aqueous solution, pH 7.5, have been studied in the temperature range 30-85 degrees C using AdoCbl tritiated at the adenine C2 position and the method of initial rates. Combined with a careful analysis of the distribution of adenine-containing products, the results permit the dissection of the competing rate constants for carbon-cobalt bond homolysis and heterolysis. After correction for the temperature-dependent occurrence of the much less reactive base-off species of AdoCbl, the activation parameters for homolysis of the base-on species were found to be delta H++homo,on = 33.8 +/- 0.2 kcal mol-1 and delta S++homo,on = 13.5 +/- 0.7 cal mol-1 K-1, values not significantly different from those determined by Hay and Finke (J. Am. Chem. Soc. 108 (1986) 4820), in the temperature range 85-115 degrees C. In contrast, the heterolysis of base-on AdoCbl was characterized by a much smaller enthalpy of activation (delta ...

Overview of Amino Acid and Organic Acid Metabolism Disorders - Etiology, pathophysiology, symptoms, signs, diagnosis & prognosis from the Merck Manuals - Medical Professional Version.

added. About LogicBio Therapeutics LogicBio Therapeutics is dedicated to extending the reach of genetic medicine with pioneering platforms. LogicBios proprietary genome editing technology platform, GeneRide, enables the site-specific integration of a therapeutic transgene without nucleases or exogenous promoters by harnessing the native process of homologous recombination. LogicBio has received FDA clearance for the first-in-human clinical trial of LB-001, a wholly owned genome editing program leveraging GeneRide for the treatment of methylmalonic acidemia. Patient enrollment in the phase 1/2 SUNRISE clinical trial is expected to begin in early 2021. In addition, LogicBio has a collaboration with Takeda to research and develop LB-301, an investigational therapy leveraging GeneRide for the treatment of the rare pediatric disease Crigler-Najjar syndrome.. LogicBio is also developing a Next Generation Capsid platform for use in gene editing and gene therapies. Data presented have shown that the ...

Metabolic & Genetic Information Center Inborn erros of metabolism METHYLMALONIC ACIDEMIA AND HOMOCYSTEINEMIA, cblX TYPE MENTAL RETARDATION, X-LINKED 3 MRX3

Examines the clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Effects of vitamin B12 deficiency on enzymatic pathways; Cnversion of homocysteine to methionine and the conversion of methylmalonyl coenzyme A to succinyl coenzyme A; Methylation reactions involving homocysteine metabolism in the nervous system.. ...

Complete information for MMADHC gene (Protein Coding), Methylmalonic Aciduria And Homocystinuria, CblD Type, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Price KE, Pearce RE, Garg UC, Heese BA, Smith LD, Sullivan JE, Kennedy MJ, Bale JF, Ward RM, Chang TK, Abbott FS, Leeder JS. Effects of valproic acid on organic acid metabolism in children: a metabolic profiling study. Clin Pharmacol Ther. 2011 Jun; 89(6):867-74 ...

Allergy Research Group features B12 Adenosylcobalamin a highly absorbable form of vitamin B12. Vitamin B12 plays a role in brain and nervous system health. Also features folic...

Vitamin B12 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.

Learn more about the history of the Illinois City County Management Association (ILCMA). Since its founding, ICMA has led the way in professional government

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