Steroidogenesis

The conversion of cholesterol to various steroids is dependent upon a number of biochemical conversions. This section highlights the biosynthesis of steroid

O CH¿OH HOCH2

Fig. 1 Schematic representation of steroid hormone biosynthesis. The substrate for steroid hormone biosynthesis is cholesterol, which is derived from low density lipoproteins (LDL), high density lipoproteins (HDL), hydrolysis of cholesterol stored in lipid droplets, or de novo synthesis. Free cholesterol is transported to the mitochondria, from where it is next transported to the inner mitochondrial membrane via steroidogenic acute regulatory protein (S) along with peripheral type benzodiazepene receptor and endozepine (not shown). Once cholesterol arrives at the inner mitochondrial membrane, it is cleaved by cytochrome P450 side chain cleavage enzyme (P450scc) to form pregnenolone, which is transported into the cytoplasm and converted by specific steroidogenic enzymes. Structures shown: progestin=progesterone; androgen=testosterone; glucocorticoid=cortisol; mineralocorticoid=aldosterone; estrogen=estradiol; vitamin D=1,25 dihydroxyvitamin D3; ACAT=acyl coenzyme A:cholesterol acyltransferase; CE=cholesterol esterase. (From Ref. 2.)

Fig. 1 Schematic representation of steroid hormone biosynthesis. The substrate for steroid hormone biosynthesis is cholesterol, which is derived from low density lipoproteins (LDL), high density lipoproteins (HDL), hydrolysis of cholesterol stored in lipid droplets, or de novo synthesis. Free cholesterol is transported to the mitochondria, from where it is next transported to the inner mitochondrial membrane via steroidogenic acute regulatory protein (S) along with peripheral type benzodiazepene receptor and endozepine (not shown). Once cholesterol arrives at the inner mitochondrial membrane, it is cleaved by cytochrome P450 side chain cleavage enzyme (P450scc) to form pregnenolone, which is transported into the cytoplasm and converted by specific steroidogenic enzymes. Structures shown: progestin=progesterone; androgen=testosterone; glucocorticoid=cortisol; mineralocorticoid=aldosterone; estrogen=estradiol; vitamin D=1,25 dihydroxyvitamin D3; ACAT=acyl coenzyme A:cholesterol acyltransferase; CE=cholesterol esterase. (From Ref. 2.)

hormones from cholesterol, with particular emphasis on the initial enzyme in the cascade: cytochrome P450 side-chain cleavage enzyme (P450scc; Fig. 1).

Once cholesterol arrives at the inner mitochondrial membrane, it is cleaved by P450scc, an enzyme complex found only in that membrane, to form pregnenolone, an intermediate product that is subsequently converted into various steroid hormones by enzymatic reactions at the level of the smooth endoplasmic reticulum. An exception to that pathway is seen in the vitamin D family, which is synthesized directly from cholesterol without conversion to pregnenolone (Fig. 1). After synthesis, steroids are secreted into the bloodstream. Because steroids are not water-soluble, they must be bound to a carrier protein to be transported to specific target tissues.[2]

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