Читать книгу Essential Endocrinology and Diabetes - Richard I. G. Holt - Страница 48

Cholesterol from the diet and from de novo synthesis (mostly in the liver) used to synthesize:

 Vitamin D (Chapter 10)

 Steroid hormones:Adrenal cortex: aldosterone, cortisol and sex steroid precursors (Chapter 6)Testis: testosterone (Chapter 7)Ovary and placenta: oestrogens and progesterone (Chapter 7)

Figure 2.5 Synthesis of cholesterol. Step ① is catalyzed by the enzyme thiolase; otherwise, the enzymes are shown to the right of the cascade. The individual steps between squalene and cholesterol have been omitted.

Figure 2.6 Overview of the major steroidogenic pathways. Yellow shading indicates the enzymatic change since the last step. The enzymes are shown by proper name and common name according to their action. Note some enzymes perform multiple reactions (e.g. CYP17A1 acts as both a hydroxylase and lyase) and some reactions are performed by multiple enzyme isoforms (e.g. HSD3B exists as HSD3B1 and HSD3B2). For 17‐OH progesterone, the enzymatic change illustrated is that catalyzed by HSD3B activity rather than CYP17A1. The simplified pathways are grouped into three blocks: (a) common to both the adrenal cortex and the gonad; (b) adrenocortical steroidogenesis; and (c) pathways characteristic of the testis (testosterone) or ovary and placenta (oestradiol). OH, hydroxy; DHEA, dehydroepiandrosterone.

In steroidogenic cells, cholesterol is largely deposited as esters in large lipid‐filled vesicles (Figure 2.3b). Upon stimulation, cholesterol is released from these stores and transported into the mitochondria, a process that is facilitated by the steroid acute regulatory (StAR) protein in the adrenal and gonad and by the related protein, start domain containing 3 (STARD3), in the placenta. The first step in the synthesis of a steroid hormone is the rate‐limiting conversion of cholesterol to pregnenolone. Pregnenolone then undergoes a range of sequential modifications in the mitochondria or the ER to produce the wide range of steroid hormones.