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Shade, collectively referred to as the Halloween enzymes (
Chavez et al., 2000;
Niwa et al., 2005; Nusslein-Volhard & Wieschaus, 1980; Petryk et al., 2003;
Warren et al., 2002, 2004
). By comparison, relatively little is known about
the reaction steps converting 7-dehydrocholesterol to 5
b
-ketodiol, commonly
known as the “Black Box.” The black box is believed to harbor the rate-limiting
step(s) of ecdysone production, and enzymes believed to act in this part of the
pathway are Shroud (a short-chain dehydrogenase/reductase), Spookier and
Cyp6t3 (both cytochrome P450 enzymes) (
Gilbert, 2004; Niwa et al., 2010;
Ono et al., 2006; Ou, Magico, & King-Jones, 2011
)(
Fig. 2.3
).
It has long been known that a small brain-derived peptide, now
known as PTTH, stimulates the production and release of ecdysone
LDLR?
Neverland
Cholesterol
Cholesterol influx
7,8-Dehydrogenase
NPC2
HO
7-Dehydrocholesterol
NPC1a
ER
Npc1a
“Black Box”
PG cell
shroud
spookier
Cyp6t3
BR-Z4
Ecdysone
OH
N
OH
HO
HO
OH
OH
Ecdysone
H
HO
?
H
O
H
H
O
MT
5
b
-Ketodiol
OH
OH
OH
OH
HO
HO
OH
H
H
O
HO
H
H
O
ER
Shade
OH
OH
OH
HO
HO
H
OH
H
O
20-Hydroxyecdysone
Peripheral tissues
Figure 2.3 A schematic diagram of ecdysone biosynthesis in the Drosophila prothoracic
gland. Cholesterol is converted into the prohormone ecdysone via a series of reactions
that occur in the ER, cytosol (suggested for other arthropod species) (
Blais et al., 1996
),
and mitochondria, represented here by stars, and exported possibly by secretory ves-
icles into hemolymph (
O'Connor, 2011
). The early gene broad (isoform BR-Z4) positively
regulates the expression of Npc1a, which encodes a cholesterol transporter mediating
the trafficking of cholesterol out of late endosomes into the ER, a critical step toward the
synthesis of ecdysone. LDLR, low-density lipoprotein receptor; MT, mitochondria; ER, en-
doplasmic reticulum; N, nucleus; PG, prothoracic gland.
