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Biosynthesis of Membrane Lipids
CHEM 4352, University of Minnesota Duluth, Johnson
86
Biochemistry
Undergraduate 3
04/13/2015

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Term
Lipid synthesis is closely tied to
Definition
gluconeogenesis and FA metabolism
Term
First step in membrane phospholipid or triacylglycerol synthesis is...
Definition
phosphatidate
Term
Where does phosphatide synthesis occur in mammals?
Definition
Outer mitochondrial membrane
In ER
Term
Glycerol 3-phosphate is primarily from...
Definition
DHAP in gluconeogenesis (to a lesser extent from glycerol phosphorylation)
Term
Glycerol phosphate acyltransferase acyl chains...
Definition
Acyl chain from acyl CoA added to C-1 (typically saturated)
Acyl chain from acyl CoA added to C-2 (typically unsaturated)
Term
What enzyme can synthesize phosphatide from diacylglycerol?
Definition
Diacylglycerol kinase
Term
Phosphatidate is present at the beginning of both...
Definition
triacylglycerol and phospholipid pathways
Term
Which two enzymes associate to form triacylglycerol synthetase complex and where is it bound?
Definition
Phosphatidic acid phosphatase
Diglyceride acyltransferase
ER membrane
Term
What does phosphatidic acid phosphatase do?
Definition
Yields diacylglycerol (DAG) from hydrolysis of phosphatidate
Term
What does diglyceride acyltransferase do?
Definition
acylates DAG
Term
Where is triacylglycerol synthesized and transported to?
Definition
Synthesized in liver
Transported to muscle and adipose tissue
Term
Where does synthesis of membrane lipids occur?
Definition
ER and Golgi
Term
What does membrane lipid synthesis require?
Definition
Diacylglycerol and an alcohol, one of them must be activated
Term
CDP diacylglycerol reacts with...
Definition
alcohol hydroxyl group
Term
CDP-diacylglycerol + inositol ->
Definition
phosphatidylinositol + CMP
Term
Kinase phosphorylations with phosphatidylinositol yield...
Definition
phosphatidylinositol 4,5-bisphosphate
Term
Cardiolipin is also called
Definition
diphosphatidylglycerol
Term
Phosphatidylglycerol + CMP ->
Definition
cardiolipin + CMP
Term
Cardiolipin located solely in..
Definition
inner mitochondrial membrane
Term
What does cardiolipin do?
Definition
organizes components of oxidative phosphorylation (stearic acid at C-1 and arachidonic acid at C-2)
Term
What is the major component of the cell membrane inner leaflet?
Definition
Phosphatidylethanolamine
Term
Phosphorylethanolamine is activated by ___ and driven by ____
Definition
CTP
Pyrophosphate hydrolysis
Term
What is the most common phospholipid in mammals?
Definition
Phosphatidylcholine
Term
If dietary choline is insufficient, where is phosphatidylethanolamine converted into phosphatidylcholine?
Definition
liver
Term
What is the source of methyl groups in the conversion of phosphatidylethanolamine to phosphatidylcholine?
Definition
S-adenosylmethionine
Term
Phosphatidylserine makes up ___% of mammalian phospholipids.
Definition
10
Term
How is phosphatidylserine formed?
Definition
formed from base exchange reaction with phosphatidylcholine or phosphatidylethanolamine
Term
Where is phosphatidylserine typically located?
Definition
inner leaflet of the lipid bilayer
Term
What happens when phosphatidylserine is moved from the inner leaflet to the outer leaflet?
Definition
Triggers apoptosis and degradation by phagocytes
Term
What is the general pattern in phosphatidylserine?
Definition
-Activated intermediate formed from phosphorylated substrate and a nucleoside triphosphate
-Activated intermediate then reacts with a hydroxyl group
Term
Sphingolipids are synthesized from...
Definition
ceramide
Term
Where is the highest concentration of ceramide located?
Definition
Nervous system
Term
What catalyzes the condensation reaction between palmitoyl CoA and serine to yield 3-ketosphinganine?
Definition
Serine-palmitoyl transferase
Term
What reduces 3-ketsphinganine to dihydrosphingosine?
Definition
NADPH
Term
The lipid group of dihydrosphingosine is transferred to the amino group of..
Definition
ceramide
Term
Sphingolipids have ____ ceramide
Definition
acylated
Term
The acyl group in sphingomyelin is...
Definition
phosphorylcholine
Term
The acyl group in cerebroside is...
Definition
glucose or galactose (from activated UDP donor)
Term
Gangliosides are...
Definition
carbohydrate-rich sphingolipids containing acid sugars
Term
Sialic acids are...
Definition
complex sphingolipids with branched oligosaccharides (at least one acidic)
Term
Gangliosides are synthesized from...
Definition
UDP-activated glucose
Galactose
N-acetylneuraminate
CMP N-acetylneuraminate
Term
What are gangliosides involved in?
Definition
inflammatory response to bind immune-system cells
Pathological mechanism of cholera toxin
Term
Sphingolipids serve as..
Definition
second messengers (cell growth, differentiation, death) and important components of lipid rafts
Term
What causes respiratory distress syndrome?
Definition
failure of dipalmitoyl phosphatidylcholine biosynthesis
Term
Where is dipalmitoyl phosphatidylcholine found?
Definition
alveoli extracellular fluid to decrease surface tension and prevent lung collapse
Term
____ is one of the most common problems for premature infants who do not make enough dipalmitoyl phosphatidylcholine.
Definition
Respiratory distress syndrome
Term
What causes Tay-Sachs?
Definition
inability to degrade gangliosides
Term
How are gangliosides degraded?
Definition
by lysosomes with sequential sugar removal
Term
Pathology of Tay-Sachs
Definition
-Swollen neurons
-Weakness and retarded psychomotor skills
-Blindness and dementia by age 2
-Death by age 3
Term
Missing or deficient ____ results in high concentration of ganglioside GM2
Definition
B-N-acetylhexosaminidase
Term
____ is a key regulatory enzyme in lipid metabolism
Definition
Phosphatidic Acid Phosphatase (PAP)
Term
___ along with ___ regulates extent and type of lipids synthesized
Definition
PAP
diacylglycerol kinase
Term
Lower PAP activation leads to...
Definition
phosphatidylinositol and cardiolipin
Term
Phosphatide regulates ____ and is a cofactor to ____
Definition
growth of ER and nuclear membrane
stimulate phospholipid synthesis genes
Term
Loss of PAP prevents ____ and causes ____, overactivity leads to _____
Definition
proper adipose-tissue development
insulin resistance
obesity
Term
Cholesterol...
Definition
-modulates membrane fluidity
-is the precursor for steroid hormones and bile salts
Term
All 27 carbon atoms in cholesterol are derived from...
Definition
acetyl CoA
Term
______ is the key building block in cholesterol biosynthesis and is located in...
Definition
Activated isoprene isopentenyl pyrophosphate
cytoplasm
Term
____ molecules combine to form squalene located in...
Definition
Six isopentenyl pyrophosphate
ER
Term
Squalene cyclizes to form ____ that is modified to yield cholesterol located in...
Definition
tetracycle
ER
Term
___ and ___ combine to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
Definition
Acetyl CoA and acetoacetyl CoA
Term
What is the fate of HMG-CoA in the mitochondria?
Definition
Converted to ketone bodies and distributed to other tissues
Term
What is the fate of HMG-CoA in the cytoplasm?
Definition
Reduced to mevalonate by HMG-CoA reductase
Term
What is the committed step in cholesterol biosynthesis and what is the equation?
Definition
Formation of mevalonate
HMG-CoA + 2NADPH + 2H+ -> mevalonate + 2NADP+ + CoA
Term
How many molecules of ATP are required to convert mevalonate to 3-isopentenyl pyrophosphate?
Definition
3
Term
The formation of squalene from 6 isopentenyl pyrophosphate molecules begins with...
Definition
isomerization to dimethylallyl pyrophosphate
Term
____ catalyzes the condensation of 2 C5 units to produce geranyl pyrophosphate (C10) and PPi
Definition
Geranyl transferase
Term
Squalene formed from ____ C15 farnesyl pyrophosphate molecules
Definition
two
Term
The _____ tail-to-tail _____ in the formation of squalene is catalyzed by ____ in the __ and has an _____ cofactor
Definition
reductive
condensation
squalene synthase
ER
NADPH
Term
____ of squalene yields lanosterol
Definition
Intramolecular cyclization
Term
The conversion of squalene to lanosterol is activated by...
Definition
conversion of squalene epoxide by squalene epoxidase
Term
____ catalyzes the concerted cyclization by protonating the epoxide oxygen, forming the hypothesized carbocation intermediate in lanosterol synthesis
Definition
Oxidosqualene cyclase
Term
Series of methyl and hydride migration quenches carbocation with the loss of a proton from ___, finally forming lanosterol
Definition
C9
Term
How many methyl groups are lost when lanosterol is converted into cholesterol?
Definition
3 (one as formate, two as CO2) and an oxidation
Term
Where are the enzymes that catalyze the conversion of lanosterol into cholesterol?
Definition
ER membrane
Term
How many steps are there in the conversion of lanosterol to cholesterol?
Definition
19
Term
____ is the major site of cholesterol biosynthesis (also the intestine)
Definition
Liver
Term
The rate of cholesterol synthesis is related to...
Definition
cellular concentration
Term
Cholesterol biosynthesis is regulated by the amount and activity of...
Definition
HMG-CoA reductase
Term
Rate of HMG-CoA reductase mRNA translation inhibited by...
Definition
mevalonate metabolites
Term
Rate of HMG-CoA reductase mRNA synthesis is controlled by...
Definition
SREBP (sterol regulating element binding protein)
Term
Progestagens (corpus luteum)
Definition
progesterone prepares lining of uterus for implantation and maintains pregnancy
Term
Androgen (testes; testosterone)
Definition
development of male secondary sex characteristics
Term
Estrogens (ovaries; estradiol)
Definition
development of female secondary sex characteristics
Term
Glucocorticoids (adrenal cortex; cortisol)
Definition
promote gluconeogenesis and glycogenesis, enhance protein and fat degradation, and inhibit inflammatory response
Term
Minterolcorticoids (adrenal cortex; aldosterone)
Definition
increase Na+ reabsorption and K+ and H+ secretion, leading to increase in blood volume and blood pressure
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