Differential HMG-CoA lyase expression in human tissues provides clues about 3-hydroxy-3-methylglutaric aciduria.
3-Hydroxy-3-methylglutaric aciduria is a rare human autosomal recessive disorder caused by deficiency of 3-hydroxy-3-methylglutaryl CoA lyase (HL). This mitochondrial enzyme catalyzes the common final step of leucine degradation and ketogenesis. Acute symptoms include vomiting, seizures and lethargy, accompanied by metabolic acidosis and hypoketotic hypoglycaemia. Such organs as the liver, brain, pancreas, and heart can also be involved. However, the pathophysiology of this disease is only partially understood. We measured mRNA levels, protein expression and enzyme activity of human HMG-CoA lyase from liver, kidney, pancreas, testis, heart, skeletal muscle, and brain. Surprisingly, the pancreas is, after the liver, the tissue with most HL activity. However, in heart and adult brain, HL activity was not detected in the mitochondrial fraction. These findings contribute to our understanding of the enzyme function and the consequences of its deficiency and suggest the need for assessment of pancreatic damage in these patients.
Laboratory of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, C/ Domingo Miral s/n, 50009, Zaragoza, Spain.
Beatriz
B
Puisac
María
M
Arnedo
Cesar H
CH
Casale
María Pilar
MP
Ribate
Tomás
T
Castiella
Feliciano J
FJ
Ramos
Antonia
A
Ribes
Celia
C
Pérez-Cerdá
Nuria
N
Casals
Fausto G
FG
Hegardt
Juan
J
Pié
D000143:Acids / Q000652:urine*; D000368:Aged; D001921:Brain / Q000201:enzymology; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D015093:Meglutol / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D007652:Oxo-Acid-Lyases / Q000235:genetics* / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism; D013737:Testis / Q000201:enzymology
D000143:Acids; D012333:RNA, Messenger; D015093:Meglutol; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase