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Bioc 460 Spring 1999
Lecture 37 - Chapter 27
- Overview
of steroid biosynthesis
- Human deficiencies in steroid biosynthesis
- Glucocorticoid regulation of PEPCK expression
Overview
of steroid biosynthesis
Cholesterol is the precursor of the five major classes of steroid hormones:
- progesterone; prepares the uterus for implantation of ovum
- androgens; male secondary sex characteristics
- estrogens; female secondary sex characteristics
- glucocorticoids; gluconeogenesis, fat mobilization
- mineralocorticoids; salt balance, kidney functions
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Figure 27.27
Progesterone is derived from cholesterol in a series of reactions removing 6 carbons. The four other major steroid hormones are derived from progesterone.
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Figure 27.30
Figure 27.31
Androstenedione - Wow, scary stuff. Read more about it.
Human deficiencies
in steroid biosynthesis
Human enzyme deficiencies have been described for a number of the enzymes required for conversion of progesterone to the other steroid hormones. These deficiencies can effect sexual development due to the substrate-production dependency of these pathways. Fortunately, steroid deficiency diseases can be treated with steroid replacement therapy.
- deficiency in 17-hydroxylase decreases levels of all steroids except mineralocorticoids. This leads to severe defects in reproductive development.
- deficiency in 21-hydroxylase is the most common defect which blocks both mineralocorticoid and glucocorticoid production. The net result is an increase in androgen production in the adrenal glands which is confounded by feedback control of hormones (ACTH) that stimulate adrenal gland growth even more. The combined effect is masculinization of females due to high levels of androgens.
- deficiency in 5a-reductase decreases production of dihydrotestosterone which is the active form of testostorone (DHT is 10x more active than testosterone). The clinical effect is feminization of males.
Cholesterol is also the precursor to vitamin D which plays an essential role in the control of bone development. The compound 7-dehydrocholesterol is photolyzed by ultraviolet light to form previtamin D3 a precursor to vitamin D3.
Rickets is a bone disease in children that is caused by vitamin D deficiency. Today milk is supplemented with vitamin D. In 17th century England there was a large number of Rickets cases before they discovered the importance of dietary supplements (cod-liver oil is rich in vitamin D) - the lack of sunlight contributed to this problem in England and also been shown to be the cause of osteomalcia (weak bones) in Bedouin Arab women who wear garments covering all but their eyes.
Figure 27.32
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Department of Biochemistry http://www.biochem.arizona.edu/classes/bioc460/spring/springindex.html
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