Alpha-aminoadipic semialdehyde synthase, mitochondrial
Domain
The N-terminal and the C-terminal domains contain respectively the lysine ketoglutarate reductase and saccharopine dehydrogenase activity.
Function
Bifunctional enzyme that catalyzes the first two steps in lysine degradation.
Involvement in disease
Hyperlysinemia, 1
HYPLYS1
An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.
None
The disease is caused by variants affecting the gene represented in this entry. In hyperlysinemia 1, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine. Some individuals, however, retain significant amounts of lysine-ketoglutarate reductase and present with saccharopinuria, a metabolic condition with few, if any, clinical manifestations.
2,4-dienoyl-CoA reductase deficiency
DECRD
A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia.
None
The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS.
Pathway
Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 1/6.
Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 2/6.
Sequence Similarities
In the N-terminal section; belongs to the AlaDH/PNT family.
In the C-terminal section; belongs to the saccharopine dehydrogenase family.
Tissue Specificity
Expressed in all 16 tissues examined with highest expression in the liver.
Cellular localization
- Mitochondrion
Alternative names
LKR/SDH, AASS