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Gene Review

ACADM  -  acyl-CoA dehydrogenase, C-4 to C-12...

Homo sapiens

Synonyms: ACAD1, MCAD, MCADH, Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
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Disease relevance of ACADM

  • Our results confirm that MCAD is one of the more common inborn errors of metabolism [1].
  • In our report of a disease-specific colonic tissue-bound antibody (CCA) from patients with ulcerative colitis (Proc Natl Acad Sci USA 1978;75:4528), crude CCA was largely fragmented, and the yield was small [2].
  • Alternatively, the cells on the paper can be rendered permeable in situ, which permits autoradiographic screening for specific biochemical defects, as reported previously for Escherichia coli [Raetz, C. R.H. (1975 Proc. Natl. Acad. Sci. USA 72, 2274-2278] [3].
  • [Gao, W.-Y., Cara, A., Gallo, R. C. & Lori, F. (1993) Proc. Natl. Acad. Sci. USA 90, 8925-8928] have suggested the use of the ribonucleotide reductase inhibitor hydroxyurea for this purpose, since the resulting decrease in the size of deoxyribonucleotide pools decreases the processivity of the HIV reverse transcriptase [4].
  • In the preceding paper [Choo, Y. & Klug, A. (1994) Proc. Natl. Acad. Sci. USA 91, 11163-11167], we showed how selections from a library of zinc fingers displayed on phage yielded fingers able to bind to a number of DNA triplets [5].

Psychiatry related information on ACADM

  • Previous measurements of label accessibility to externally added ascorbate had been considered to suggest an external-internal transition of protein-bound labels, coupled with ion translocation [Tonomura, Y. & Morales, M.F. (1974) Proc. Natl. Acad. Sci. USA 71, 3687-3691] [6].
  • Metal ions have been hypothesized to play a role in the formation and neurotoxicity of aggregates associated with Alzheimer's disease (Bush, A. I.; et al. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 11934) [7].
  • Previous studies have shown that in advanced cases of Huntington's disease, enkephalin-immunoreactive striatal projections to the external globus pallidus may be more affected than substance P-containing striatal projections to the inner segment of the pallidum [Reiner A. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 5733-5737] [8].
  • A region between D13S71 and D13S274 on 13q32 showed linkage to bipolar disorder (BP) based on a genome scan using markers with an average spacing of approximately 6 cM and an average heterozygosity of approximately 60% [Detera-Wadleigh et al., 1999: Proc Natl Acad Sci USA 96:5604-5609] [9].
  • (J Am Acad Dermatol 2002;46:807-21.) Learning objective: At the conclusion of this learning activity, participants should be familiar with clinical and histologic aspects of trichotillomania and should be able to cope with the risks of medical and psychiatric complications in these patients [10].

High impact information on ACADM

  • This selection favors B cell expressing surface immunoglobulins with VHa2 structures in the first and third framework regions (Pospisil, R., G.O. Young-Cooper, and R.G. Mage. 1995. Proc. Natl. Acad. Sci. USA. 92:6961-6965) [11].
  • The restricted expression of Thy-1 on primitive hematopoietic cells is in agreement with a previous report (Baum et al., 1992. Proc. Natl. Acad. Sci. USA. 89:2804) in which Thy-1 expression was used to enrich for primitive hematopoietic cells from fetal tissue [12].
  • A 1% sequence variability among different isolates of the pathogenic strain HM1:IMSS and a 12-13% variability between pathogenic and nonpathogenic strains are revealed by comparison to published partial amino acid sequences (Tannich, E., R.D. Horstmann, J. Knobloch, and H.H. Arnold. 1989. Proc. Natl. Acad. Sci. USA. 86:5118) [13].
  • Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765) [14].
  • In a previous study we provide evidence for a circuitous pathway by which circulating plasma proteins enter megakaryocyte granules by an endocytic mechanism and are returned to the circulation in platelets (1987. Proc. Natl. Acad. Sci. USA. 84:861-865) [15].

Chemical compound and disease context of ACADM

  • Pathogenic strains of Escherichia coli and Salmonella enterica modify the tricatecholic siderophore enterobactin (Ent) by glucosylation of three aryl carbon atoms, a process controlled by the iroA locus [Hantke, K., Nicholson, G., Rabsch, W. & Winkelmann, G. (2003) Proc. Natl. Acad. Sci. USA 100, 3677-3682] [16].
  • [Okamura, M. Y., Isaacson, R. A., & Feher, G. (1975) Proc. Natl. Acad. Sci. USA 88, 3491-3495], who were able to extract with detergents the firmly bound ubiquinone Q(A) from the RC of Rhodobacter sphaeroides and reconstitute the site with extraneous quinones [17].
  • Conditions, such as anoxia or glucose starvation, which induce the glucose-regulated set of stress proteins also lead to resistance to adriamycin (J. Shen, C. Hughes, C. Chao, J. Cai, C. Bartels, T. Gessner, and J. Subjeck, Proc. Natl. Acad. Sci. USA 84:3278-3282, 1987) and etoposide [18].
  • We previously purified and characterized functionally the Escherichia coli-expressed product of the human subgroup C adenovirus E1A 13S mRNA (B. Ferguson, N. Jones, J. Richter, and M. Rosenberg, Science 224:1343-1346, 1984; B. Krippl, B. Ferguson, M. Rosenberg, and H. Westphal, Proc. Natl. Acad. Sci. USA 81:6988-6992, 1984) [19].
  • Previous studies have shown that the extent of platinum-DNA adduct formation measured in WBC DNA of ovarian cancer patients treated with cisplatin or carboplatin is directly associated with disease response (Reed et al., Proc. Natl. Acad. Sci. USA, 84: 5024-5028, 1987) [20].

Biological context of ACADM

  • By linkage studies, the orientation of these three loci relative to the centromere places ACADM most proximal [21].
  • A partial amino acid sequence (137 residues) determined on peptides derived from MCAD purified from porcine liver confirmed the identity of the cDNA clone [22].
  • The MCAD mRNA nucleotide sequence was determined from two overlapping cDNA clones isolated from human liver and placental cDNA libraries, respectively [22].
  • Definition of the primary structure of MCAD and the tissue distribution of its mRNA is of biochemical and clinical importance because of the recent recognition of inherited MCAD deficiency in humans [22].
  • We have previously shown that the mRNA encoding MCAD in an MCAD-deficient child is homozygous for the point mutation A985 to G [Kelly et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9236-9420] [23].

Anatomical context of ACADM


Associations of ACADM with chemical compounds

  • METHOD: Biochemical genetic testing including plasma acylcarnitine and urine acylglycine analyses, as well as sequencing of ACADM was performed in a Korean family with a newborn who had an elevated octanoyl (C8) carnitine concentration by newborn screening (NBS) [28].
  • These show statistically lower acylcarnitine markers, allowing us to distinguish subgroups within the spectrum of ACADM sequence variations that correlate to biochemical MCADD disease expression [29].
  • Recently, we showed that IBP-s consists of several members of the steroid/thyroid hormone receptor superfamily (F. Zuo and J. E. Mertz, Proc. Natl. Acad. Sci. USA 92:8586-8590, 1995) [30].
  • Concomitantly, mRNA expression of enzymes of fatty acid oxidation (medium-chain acyl CoA dehydrogenase, MCAD; carnitine palmitoyl transferase I, CPT-I) was reduced in TG1306/R1 compared with age-matched WT mice [31].
  • We have already demonstrated that a hyperinsulinemic, diabetic subject secreted an abnormal insulin in which serine replaced phenylalanine B24 (Shoelson S., M. Fickova, M. Haneda, A. Nahum, G. Musso, E. T. Kaiser, A. H. Rubenstein, and H. Tager. 1983. Proc. Natl. Acad. Sci. USA. 80:7390-7394) [32].

Other interactions of ACADM


Analytical, diagnostic and therapeutic context of ACADM

  • This makes ACADM informative for linkage mapping and for clinical genetic studies [21].
  • We were recently able to identify, using site-directed mutagenesis, amino acids in the binding subunit of these toxins that are important in defining their glycosphingolipid (GSL) binding specificity (Tyrrell, G. J., K. Ramotar, B. Boyd, B. W. Toye, C. A. Lingwood, and J. L. Brunton. 1992. Proc. Natl. Acad. Sci. USA. 89:524) [33].
  • [Chang, A.C.Y., Cochet, M. & Cohen, S.W. (1980) Proc. Natl. Acad. Sci. USA 77,4890-4894] but agrees with the structure recently derived by direct sequence analysis by Hsi et al [34].
  • Tryptic peptide mapping showed that this polypeptide is related to a Mr 24,000 polypeptide identified as CBP in earlier experiments [Sonenberg, N., Morgan, M. A., Testa, D., Colonna, R. J. & Shatkin, A. J. (1978) Proc. Natl. Acad. Sci. USA 75, 4843-4847] [35].
  • Electrophoretic mobility-shift assays performed with MCAD promoter fragments and nuclear protein extracts prepared from hypertrophied and control RV identified pressure overload-induced protein/DNA interactions at a regulatory unit shown previously to confer control of MCAD gene transcription during cardiac development [36].


  1. Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. Ziadeh, R., Hoffman, E.P., Finegold, D.N., Hoop, R.C., Brackett, J.C., Strauss, A.W., Naylor, E.W. Pediatr. Res. (1995) [Pubmed]
  2. Detection of colonic antigen(s) in tissues from ulcerative colitis using purified colitis colon tissue-bound IgG (CCA-IgG). Nagai, T., Das, K.M. Gastroenterology (1981) [Pubmed]
  3. Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper. Esko, J.D., Raetz, C.R. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  4. Inhibition of ribonucleotide reductase by 2'-substituted deoxycytidine analogs: possible application in AIDS treatment. Bianchi, V., Borella, S., Calderazzo, F., Ferraro, P., Chieco Bianchi, L., Reichard, P. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Selection of DNA binding sites for zinc fingers using rationally randomized DNA reveals coded interactions. Choo, Y., Klug, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Calcium translocation mechanism in sarcoplasmic reticulum vesicles, deduced from location studies of protein-bound spin labels. Champeil, P., Rigaud, J.L., Gary-Bobo, C.M. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  7. Amyloid-beta binds Cu2+ in a mononuclear metal ion binding site. Karr, J.W., Kaupp, L.J., Szalai, V.A. J. Am. Chem. Soc. (2004) [Pubmed]
  8. Evidence for a preferential loss of enkephalin immunoreactivity in the external globus pallidus in low grade Huntington's disease using high resolution image analysis. Sapp, E., Ge, P., Aizawa, H., Bird, E., Penney, J., Young, A.B., Vonsattel, J.P., DiFiglia, M. Neuroscience (1995) [Pubmed]
  9. Fine mapping supports previous linkage evidence for a bipolar disorder susceptibility locus on 13q32. Liu, C., Badner, J.A., Christian, S.L., Guroff, J.J., Detera-Wadleigh, S.D., Gershon, E.S. Am. J. Med. Genet. (2001) [Pubmed]
  10. Trichotillomania. Hautmann, G., Hercogova, J., Lotti, T. J. Am. Acad. Dermatol. (2002) [Pubmed]
  11. CD5 is a potential selecting ligand for B cell surface immunoglobulin framework region sequences. Pospisil, R., Fitts, M.G., Mage, R.G. J. Exp. Med. (1996) [Pubmed]
  12. Expression of Thy-1 on human hematopoietic progenitor cells. Craig, W., Kay, R., Cutler, R.L., Lansdorp, P.M. J. Exp. Med. (1993) [Pubmed]
  13. Characterization of an immuno-dominant variable surface antigen from pathogenic and nonpathogenic Entamoeba histolytica. Edman, U., Meraz, M.A., Rausser, S., Agabian, N., Meza, I. J. Exp. Med. (1990) [Pubmed]
  14. Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. Murata, M., Russell, S.R., Ruggeri, Z.M., Ware, J. J. Clin. Invest. (1993) [Pubmed]
  15. Incorporation of intravenously injected albumin, immunoglobulin G, and fibrinogen in guinea pig megakaryocyte granules. Handagama, P.J., Shuman, M.A., Bainton, D.F. J. Clin. Invest. (1989) [Pubmed]
  16. In vitro characterization of IroB, a pathogen-associated C-glycosyltransferase. Fischbach, M.A., Lin, H., Liu, D.R., Walsh, C.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  17. Efficient exchange of the primary quinone acceptor Q(A)in isolated reaction centers of Rhodopseudomonas viridis. Breton, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Depletion of topoisomerase II in isolated nuclei during a glucose-regulated stress response. Shen, J.W., Subjeck, J.R., Lock, R.B., Ross, W.E. Mol. Cell. Biol. (1989) [Pubmed]
  19. E1A 13S and 12S mRNA products made in Escherichia coli both function as nucleus-localized transcription activators but do not directly bind DNA. Ferguson, B., Krippl, B., Andrisani, O., Jones, N., Westphal, H., Rosenberg, M. Mol. Cell. Biol. (1985) [Pubmed]
  20. Evaluation of platinum-DNA adduct levels relative to known prognostic variables in a cohort of ovarian cancer patients. Reed, E., Ostchega, Y., Steinberg, S.M., Yuspa, S.H., Young, R.C., Ozols, R.F., Poirier, M.C. Cancer Res. (1990) [Pubmed]
  21. The locus for the medium-chain acyl-CoA dehydrogenase gene on chromosome 1 is highly polymorphic. Kidd, J.R., Matsubara, Y., Castiglione, C.M., Tanaka, K., Kidd, K.K. Genomics (1990) [Pubmed]
  22. Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. Kelly, D.P., Kim, J.J., Billadello, J.J., Hainline, B.E., Chu, T.W., Strauss, A.W. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  23. Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene. Zhang, Z.F., Kelly, D.P., Kim, J.J., Zhou, Y.Q., Ogden, M.L., Whelan, A.J., Strauss, A.W. Biochemistry (1992) [Pubmed]
  24. Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Horowitz, J.F., Leone, T.C., Feng, W., Kelly, D.P., Klein, S. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  25. Effects of insulin-like growth factor-I on the maturation of metabolism in neonatal rat cardiomyocytes. Montessuit, C., Palma, T., Viglino, C., Pellieux, C., Lerch, R. Pflugers Arch. (2006) [Pubmed]
  26. Pioglitazone induces de novo ceramide synthesis in the rat heart. Baranowski, M., Blachnio, A., Zabielski, P., Gorski, J. Prostaglandins Other Lipid Mediat. (2007) [Pubmed]
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  28. Genotypic differences of MCAD deficiency in the Asian population: novel genotype and clinical symptoms preceding newborn screening notification. Ensenauer, R., Winters, J.L., Parton, P.A., Kronn, D.F., Kim, J.W., Matern, D., Rinaldo, P., Hahn, S.H. Genet. Med. (2005) [Pubmed]
  29. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Maier, E.M., Liebl, B., Röschinger, W., Nennstiel-Ratzel, U., Fingerhut, R., Olgemöller, B., Busch, U., Krone, N., v Kries, R., Roscher, A.A. Hum. Mutat. (2005) [Pubmed]
  30. Direct modulation of simian virus 40 late gene expression by thyroid hormone and its receptor. Zuo, F., Kraus, R.J., Gulick, T., Moore, D.D., Mertz, J.E. J. Virol. (1997) [Pubmed]
  31. Overexpression of angiotensinogen in the myocardium induces downregulation of the fatty acid oxidation pathway. Pellieux, C., Aasum, E., Larsen, T.S., Montessuit, C., Papageorgiou, I., Pedrazzini, T., Lerch, R. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  32. Human insulin B24 (Phe----Ser). Secretion and metabolic clearance of the abnormal insulin in man and in a dog model. Shoelson, S.E., Polonsky, K.S., Zeidler, A., Rubenstein, A.H., Tager, H.S. J. Clin. Invest. (1984) [Pubmed]
  33. Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targetting and results in a verotoxin 1-like disease in pigs. Boyd, B., Tyrrell, G., Maloney, M., Gyles, C., Brunton, J., Lingwood, C. J. Exp. Med. (1993) [Pubmed]
  34. NH2-terminal amino acid sequence and peptide mapping of purified human beta-lipotropin: comparison with previously proposed sequences. Spiess, J., Mount, C.D., Nicholson, W.E., Orth, D.N. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  35. Association of a Mr 50,000 cap-binding protein with the cytoskeleton in baby hamster kidney cells. Zumbé, A., Stähli, C., Trachsel, H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  36. A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Sack, M.N., Disch, D.L., Rockman, H.A., Kelly, D.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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