Chapter 26 Flashcards
common intermediate in the synthesis of phospholipids and triglyceride
phosphatidate
phosphatidate formed from ?
addition of two fatty acids to glycerol phosphate
glycerol phosphate produced from ?
reduction of DHAP or phosphorylation of glycerol
membrane lipids are synthesized here
on the cytosolic leaflet of the ER
pathway from phosphatidate to TAG
phosphatidate >(lipid phosphate phosphohydrolase)> DAG >(DAG acyltransferase)> TAG
TAG are primarily synthesized in ? and transported to ?
liver. adipose and muscle.
triacylglycerol synthetase complex contains
lipid phosphate phosphohydrolase and DAG acyltransferase
activation of phosphatidate or alcohol with ? is required to make phospholipids. Uses ? enzyme
CTP. phosphatidate cytidyltransferase
phosphatidylinositol synthase reaction catalyzed
CDP-DAG + inositol»_space; phosphatidylinositol + CMP
synthesis of phospholipid starting with an alcohol
alcohol activated with CTP. Attached to DAG.
most common phospholipid in animals
phosphatidylcholine
phosphatidylcholine pathway
ethanolamine activated with CTP and attached to DAG. Addition of 3S-adenosylmethionine by liver methyltransferase
sphingolipids are synthesized from ?
ceramide
prominent lipid in the myelin sheath of nerve fibers
sphingomyelin
ganglioside structures
ceramide with sugar chain
in all sphingolipids, ? of ceramide is acylated
amino
dipalmitoyl phosphatidylcholine is synthesized in the lung as a ?. Impaired synthesis results in ?
surfacant. respiratory distress syndrome.
tay-sachs disease results from loss of ? involved in the degradation of ?
N-acetylhexoseaminadase. gangliosides
carbons of cholesterol from acetyl CoA in 3 steps
1) synth of isopentyl pyrophosphate in cyto 2) condensation of 6 isopentyl-PP to form squalene in ER 3) cyclization of squalene and conversion to cholesterol in the ER
? is a branch point in lipid metabolism
HMG-CoA
HMG-CoA synthetase reaction catalyzed
acetoacetyl CoA + acetyl CoA»_space; HMG-CoA
site of most cholesterol biosynthesis
liver
HMG-CoA reductase reaction (committed step in cholesterol synthesis)
HMG-CoA + 2NADPH»_space; mevalonate
HMG-CoA is an integral membrane protein of ?
ER
? is the mitochondrial enzyme used in the production of ketone bodies
HMG-CoA lyase
HMG-CoA lyase reaction catalyzed
HMG-CoA»_space; Acetyl-CoA + Acetoacetate (ketone bodies)
mevalonate undergoes three rounds of phosphorylation to obtain ?
3-isopentyl pyrophosphate
isopentyl PP isomerizes to ?
dimethylallyl PP
synthesis of squalene
two C5 units (dimethylallyl PP and isopentyl PP) combine in head to tail condensation to give C10 unit. Additon of another isopentyl PP to give C15 unit. Two C15 units combine to form squalene.
? activates squalene, then ? initiates converted ring closures to make lanosterol
squalene epoxidase. oxidosqualene cyclase.
conversion of lanosterol to cholesterol
removes three methyl groups. reduction of one double bond. migration of one double bond.
regulation of HMG-CoA reductase
low ATP reduces synthesis. inhibited by statin family.
Activation of transcription of HMG CoA reductase mRNA
SREBP transcription factor is synthesized as membrane protein precursor. when cholesterol low, SREBP is released to bind to SRE to enhance transcription
SCAP
SREBP cleavage activating protein
statins are ? analogs
HMG
cholesterol and TAGs are packaged into ? for transport between tissues
lipoprotein complexes
delivery/”bad” forms of cholesterol
VLDL and LDL
return/”good” form of choleserol
HDL
HDL
sends cholesterol from dying cells and membranes undergoing turnover to liver for excretion
LDL
main carrier of cholesterol in blood and regulate de novo synthesis
healthy HDL:LDL ratio
3.5
? mature into LDL
VLDL
uptake of LDL particles via the LDL receptor is the paradigm for ?
receptor-mediated endocytosis
excess cholesterol leads to ?
artherosclerosis
management of high levels of cholesterol
statins reduce de novo synthesis. deduce dietary cholesterol. inhibition of cholesterol uptake by postively charged polymers (like cholestyramine)
cholestyramine results in ?
excretion of bile acids requiring cells to synthesize new bile acids from cholesterol
bile salts
polar derivatives of cholesterol that solubilize dietary lipids
cholesterol is the precursor of ?
steroid hormones
glucocorticoids
promote gluconeogenesis
hydroxylations of cholesterol are performed by ?
cytochrome P450 monooxygenases
?# of varieties of cytochrome P450 monooxygenases
57
members of P450 monooxygenases are ? proteins
membrane associated hemes
P450 monooxygenases reaction uses both ? and ?
oxygen and NADPH
P450 monooxygenases mechanism
substrate binds. andrenodoxin reduces heme Fe. O2 binds. andrenodoxin reduces O2. Cleavage of O-O bond releases water. ROS abstracts H to create radical. radical grabs OH.
P450 can also detoxify foreign substances by ?
increasing solubility
7-dehrocholesterol is converted into ? by UV light
vitD
vitamin D is converted to ? which regulates ?
calcitriol. regulates Ca++ uptake
