3- Hydroxy-3-methylglutaryl CoA lyase

Roberts, J.R. and Miziorko, H.M. 1997. Evidence supporting a role for histidine-235 in cation binding to human 3-hydroxy-3-methylglutaryl-CoA lyase. Biochemistry 36 7594—7600. 

A very similar reaction is catalyzed by 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase), which functions in the formation of acetoacetate in the human body (Eq. 17-5, step c) and also in the catabolism of leucine (Fig. 24-18)182183 and in the synthesis of 3-hydroxy-3-methyIgIutaryI-CoA, the presursor of cholesterol (Eq. 17-5, step fr)183a... 

Figure 20-3. Pathway for the catabolism of leucine. The last step in the pathway is catalyzed by 3-hydroxy-3methyl-CoA lyase, which is deficient in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

Nyhan WL, Barshop BA, Ozand PT 3-Hydroxy-3-methylglutaryl CoA lyase deficiency, in Nyhan WL, Barshop BA, Ozand PT (eds) Atlas of Metabolic Diseases, 2nd edition. Chapman and Half Medical, 2005, pp. 253-258. 

Kramer, P. R., and Miziorko, H. M. (1983). 3-Hydroxy-3-methylglutaryl-CoA lyase Catalysis of acetyl coenzyme A enolization. Biochemistry 22, 2353-2357. 

Methylcrotonylglycinuria 3-Methylglutaconic aciduria, type 1 3-Methylglutaconic aciduria, other types 3-Hydroxy-3-methylglutaryl-CoA lyase def Biotinidase def... 

Wang, S. P., Marth, J.D., Oligny, L.L. et al. (1998) 3-Hydroxy-3-methylglutaryl-CoA lyase (HL) gene targeting causes prenatal lethality in HL-deficient mice. Hum. Mo-lec. Genet, 7, 2057-2062. 

Hydroxy-3-methylglutaric aciduria 3-Methylglutaconic, 3-hydroxy-3-methylglutaric, 3-hydroxyiso-valeric and 3-methylglutaric acids 3-Hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4) 10.3.4... 

Duran, M., Schutgens, R.B.H., Ketel, A., Heymans, H., Bemtssen, M.W.J., Ketting, D. and Wadman, S.K. (1979), 3-Hydroxy-3-methylglutaryl CoA lyase deficiency Postnatal management following prenatal diagnosis by analysis of maternal urine. J. Pediatr., 95,1004. 

Hydroxy-3-methylglutaryl-CoA lyase deficiency, leading to 3-hydroxy-3-methylglutaric aciduria... 

Despite the prolific literature on this abnormal organic aciduria, there have been only three authenticated cases of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency reported. 

Table 10.3 Organic acid concentrations in urine from a patient with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (after Duran 1978a Schutgens era/., 1978).

These brief reports have been confirmed by a more detailed description of a similar case (Truscott et al, 1979), a girl who died at 5 days of age with hyperammonaemia, and raised plasma glutamine, alanine and lysine. Increased excretion of 3-methylglutaric, 3-methylglutaconic and 3-hydroxy-3-methylglutaric acids (but not of 3-hydroxyisovaleric acid) was observed but at much lower concentrations than those in patients with authentic 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, being 170,463 and 181 mmol mol of creatinine respectively or 20 per cent, 6 per cent and 1 per cent of the concentrations in an authentic patient. Measurement of enzyme activities in cultured fibroblasts showed these to be normal and a primary defect in the urea cycle was suspected ... 

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