30 Questions
Which enzyme catalyzes the hydroxylation of C17 of progesterone or pregnenolone and can also catalyze the cleavage of the two-carbon side chain of these compounds at C17?
P450C17 (CYP17)
Which layer of the adrenal cortex is involved in the synthesis of cortisol?
Zona fasciculata
What is the precursor of androstenedione in the pathway of cortisol synthesis?
17-α-hydroxyprogesterone
Which compound is transported to the smooth ER along with progesterone in the pathway of cortisol synthesis?
17-α-hydroxyprogesterone
Which steroids are precursors of androgens and estrogens in the adrenal cortex?
C19 steroids
Where is free cholesterol transported to initiate cortisol synthesis?
Inner mitochondrial membrane
Which enzyme is responsible for the conversion of testosterone to dihydrotestosterone (DHT) in target cells?
5-α-reductase
Where is approximately 50% of testosterone produced in a normal woman?
Ovaries and adrenal cortices
Which organ is the major source of the relatively weak androgen dehydroepiandrosterone (DHEA)?
Adrenal cortex
What deficiency causes rickets, resulting in low levels of calcium and phosphorus in the blood and skeletal deformities in children?
Vitamin D
Where does the formation of active vitamin D (calcitriol) from cholecalciferol begin and end?
Begins in the liver and ends in the kidney
Which medication reduces the amount of cholesterol available to the enterocyte to package into chylomicrons?
Ezetimibe
Which hormone stimulates adrenal cortical cells in the zona fasciculata to produce cortisol?
Adrenocorticotropic hormone (ACTH)
What is the predominant pathway for testosterone synthesis in the testicle?
Pregnenolone to DHEA to androstenedione to testosterone
What may lead to clinical signs of mineralocorticoid excess even with suppressed aldosterone secretion?
Excessive production of the weaker mineralocorticoid, DOC
What is the primary stimulus for aldosterone production?
Angiotensin II
What results from genetically determined deficiencies in enzymes required for cortisol synthesis?
Congenital adrenal hyperplasia (CAH)
What is the first step in aldosterone synthesis?
Conversion of cholesterol to progesterone
What is the recommended use of low-dose aspirin according to the 2019 ACC/AHA guideline?
For select higher risk ASCVD adults aged 40 to 70 years
What is the effect of glucocorticoid therapy with prednisone in a patient with nonclassic congenital adrenal hyperplasia?
Resolved virilizing features
What is the consequence of loss of LKB1 protein activity?
Development of Peutz–Jeghers syndrome (PJS)
What is the role of LKB1 protein in regulating kinase activity?
Regulates activity of 14 kinases including AMP-activated protein kinase
What is the effect of metformin on AMP-activated protein kinase (AMPK)?
Activates AMPK by activating LKB1
What is the overall effect of AMPK activation?
Reduces fatty acid synthesis, cholesterol biosynthesis, liver gluconeogenesis, and lipogenesis
Which enzyme catalyzes the conversion of HMG-CoA to mevalonic acid, the regulated and rate-limiting step of cholesterol biosynthesis?
HMG-CoA reductase
Which drug inhibits MTP, reducing circulating chylomicron and VLDL levels, resulting in a 50% drop in circulating LDL levels?
Lomitapide
Which molecule functions to transfer apolipoprotein E and apolipoprotein CII to nascent chylomicrons and VLDL, and participates in reverse cholesterol transport?
HDL
Which molecule is required for fat emulsification and micelle formation in the small intestine, and is recycled via the enterohepatic circulation, forming the secondary bile acids?
Bile salts
Which molecule is responsible for enhancing fatty acid transport and degradation, leading to a reduction of circulating lipoprotein particles?
PPARα
Which activity reduces fatty acid synthesis, inhibits key lipogenic enzymes, and decreases transcription of SREBP-1, mediated via an AMPK inhibition of the transcription of SREBP-1?
AMPK
Study Notes
Lipid Metabolism and Drug Targets
- AMPK activity reduces fatty acid synthesis, inhibits key lipogenic enzymes, and decreases transcription of SREBP-1, mediated via an AMPK inhibition of the transcription of SREBP-1.
- Fibrates decrease lipid levels, principally triglycerides, by targeting PPARα, leading to enhanced fatty acid transport and degradation, and reduction of circulating lipoprotein particles.
- Thiazolidinediones activate PPARγ, leading to increased circulating adiponectin levels, reduced fat content in the liver, and enhanced insulin sensitivity via an AMPK-dependent pathway.
- Lomitapide inhibits MTP, reducing circulating chylomicron and VLDL levels, resulting in a 50% drop in circulating LDL levels, while mipomersen blocks apolipoprotein B-100 synthesis, leading to a 25% drop in LDL levels.
- Cholesterol regulates membrane fluidity, is a precursor of bile salts, steroid hormones, and vitamin D, and is transported in the blood as a component of lipoproteins.
- De novo cholesterol synthesis requires acetyl CoA as a precursor and is packaged into VLDL in the liver and released into circulation.
- HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, the regulated and rate-limiting step of cholesterol biosynthesis.
- In the circulation, lipoprotein lipase digests triglycerides in VLDL, converting the particle to IDL and then to LDL, which binds specifically to receptors on liver cells and are internalized.
- HDL functions to transfer apolipoprotein E and apolipoprotein CII to nascent chylomicrons and VLDL, and participates in reverse cholesterol transport, returning cholesterol to the liver.
- Atherosclerotic plaques are associated with elevated blood cholesterol levels, with high levels of LDL being more strongly associated with plaque generation, and high levels of HDL being protective.
- Bile salts are required for fat emulsification and micelle formation in the small intestine, and are recycled via the enterohepatic circulation, forming the secondary bile acids.
- Lipid-lowering drugs act on various targets within the liver, intestine, and adipocytes, and diseases discussed in this chapter are summarized in Table 32.7.
Test your knowledge of lipid metabolism and drug targets with this quiz! Explore key concepts such as AMPK activity, PPAR activation, cholesterol synthesis, lipoprotein metabolism, and the role of lipid-lowering drugs in managing lipid levels.
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