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Cholesterol and bile metabolism
Terms in this set (21)
What is a cholesterol ester?
A normal cholesterol molecule esterified with a long-chain fatty acid
Cholesterol is synthesized in the? (list organs)
Liver, intestine, adrenal cortex, reproductive tissues
What is the precursor to cholesterol biosynthesis?
Cytosolic acetyl CoA
In the biosynthesis of cholesterol, acetyl coA is converted to _________ coA, which is then converted to ______ coA. The first enzyme is ________, while the second enzyme is _____________.
Acetoacetyl coA, HMG coA, thiolase, HMG coA synthase
The HMG pathway is also present in synthesis of _______; the difference is that the cholesterol biosynthesis one takes place in the cytoplasm, while the ______ metabolism one takes place in the mitochondrion of the liver.
HMG coA is converted to _________. This is the committed and regulated step of cholesterol synthesis. The enzyme responsible is ____________.
Mevalonate, HMG coA reductase
Since production of mevalonate is a highly regulated step, the principal enzyme, ____________, can be regulated by 3 ways:
HMG coA reductase, transcription of the gene, degradation of the protein, phosphorylation of the protein
Transcriptional regulation of cholesterol biosynthesis is achieved through _________, a binding protein, and ______, its target.
SREBP (Sterol regulatory element binding protein), SCAP (SREBP cleavage-activating protein)
Binding of INSIG1 (insulin-induced gene 1) to SCAP keeps the complex where in the cell?
Addition of sterols to the HMG-CoA reductase causes it to be flagged for __________ and eventual _________.
Cholesterol synthesis can also be regulated by phosphorylation. In this instance, HMG CoA reductase is in the ____ membrane with the C-terminal portion in the _________. Phosphorylation of the C-terminal domain causes the molecule to become _________.
ER, cytoplasm, inactive
Mevalonate can be converted to active _______ units. These units are required for the synthesis of dolichol, ubiquinone, and cholesterol. Dolichol is required for N-linked _________ of proteins.
___ activated isoprene units are required to form the ___-carbon squalene unit. The process proceeds by two isoprene units forming a geranyl phosphate. Geranyl phosphate condenses with another isopentynyl pyrophosphate to form _______ pyrophosphate. The enzyme for this process is ________ transferase.
6, 30, farnesyl, geranyl
Farnesyl pyrophosphate + farnesyl pyrophosphate = ?
Squalene (30 carbons)
Proteins become prenylated when we add molecules such as ________ and _______ pyrophosphate. The proteins have many functions. _______ inhibit prenylation.
Geranyl, farnesyl, statins
Squalene is converted to _______. This reaction occurs in the ER. The enzyme is a ________-based system. The end product has 4 fused rings.
Lanosterol is converted to ________. In the reaction (not important), _ methyl groups are lost, as well as migration of a double bond.
Once produced, cholesterol is synthesized into ___________. This product is packaged into lipoproteins. The product is made using the enzyme ___________. A majority remains in the liver, where it is used in the formation of ______.
Cholesteryl esters, acyl-CoA cholesterol acyl transferase, bile
Familial hypercholesterolemia is caused by?
A defective LDL receptor
7-dehydrocholesterol reductase deficiency (inability to produce cholesterol) d/t mutation on DHCR7 gene
1 in 30,000
Diagnosis: measure serum 7-DHC (high, as no 7-DHC reductase to break down to cholesterol)
FACE: microcephaly, broad nasal tip with anteverted nostrils, micrognathia, ptosis, epicanthal folds, cataracts, broad maxillary alveolar ridges, low-set ears, cleft palate
BODY: short stature, hypotonia, syndactyly of 2nd/3rd toes, polydactyly, hypospadias
HEART: VSD + PDA
Bile acids are ___ carbons with a ______ group at the end. The hydroxyl and methyl groups are in separate planes. Therefore, the molecule has both a polar and nonpolar surface. The rate limiting step is the enzyme _________.
24, carboxyl, 7-alpha-hydroxylase
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