DECR1

DECR1 Full Name

2,4-dienoyl CoA reductase 1, mitochondrial

DECR1 Introduction

DECR1, officially designated as 2,4-dienoyl CoA reductase 1, is a mitochondrial matrix enzyme that belongs to the short-chain dehydrogenase/reductase (SDR) superfamily. Its gene is located on human chromosome 8q21.3, encoding a 335-amino acid polypeptide that incorporates an N-terminal mitochondrial targeting sequence. Once imported into the organelle, the mature protein adopts a typical Rossmann fold for cofactor binding, utilizing NADPH as its preferred electron donor. This subcellular residency is biologically critical, as it places DECR1 precisely within the β-oxidation spiral, where it intercepts and processes unsaturated fatty acyl intermediates. The enzyme's structural integrity and cofactor specificity are highly conserved across metazoans, reflecting its ancient evolutionary role in lipid metabolism.

Figure1. Structure of DECR1.

Biochemical Catalytic Mechanism
The primary reaction catalyzed by DECR1 involves the NADPH-dependent reduction of double bonds at even-numbered carbon positions within unsaturated fatty acyl-CoA esters, specifically transforming 2,4-dienoyl-CoA intermediates into 3-enoyl-CoA products. This step is stereospecific, with the hydride delivered to the β-carbon of the substrate, effectively shifting the unsaturation pattern to allow further degradation by the main β-oxidation cycle. Unlike acyl-CoA dehydrogenases, which introduce double bonds, DECR1 acts as a reductase to remove them, making it an auxiliary but indispensable enzyme for polyunsaturated fatty acid oxidation. Its catalytic efficiency depends on optimal pH and ionic conditions within the matrix, and it operates in tight metabolic coordination with enoyl-CoA isomerases to ensure complete breakdown of dietary and stored unsaturated fats.

Physiological Role in Fatty Acid β-Oxidation
In living organisms, DECR1 is the gatekeeper for oxidizing long-chain polyunsaturated fatty acids (PUFAs) such as linoleic and arachidonic acids, which contain multiple cis-double bonds that stall standard β-oxidation. Without this reductase, the degradation of these essential fatty acids would cease at the 2,4-dienoyl intermediate, leading to metabolic bottleneck and accumulation of potentially toxic lipid species. The enzyme is particularly active in tissues with high oxidative demands, including cardiac muscle, skeletal muscle, and brown adipose tissue, where PUFAs serve as significant energy sources. Furthermore, DECR1 contributes to the regulation of cellular lipid homeostasis by preventing the aberrant incorporation of partially oxidized acyl chains into membrane phospholipids. Its activity thus directly influences both energy production and membrane fluidity maintenance.

Alternate Names for DECR1

DECR1; 2,4-dienoyl CoA reductase 1, mitochondrial; DECR; 2,4-dienoyl-CoA reductase, mitochondrial; SDR18C1; short chain dehydrogenase/reductase family 18C; member 1; 4-enoyl-CoA reductase; short chain dehydrogenase/reductase family 18C, member 1; NADPH;