Lipid Metabolism II Flashcards
What is the major source of carbon for fatty acid synthesis?
dietary carbohydrates
where does fatty acid synthesis primarily occur?
liver
where does fatty acid synthesis also occur?
brain, kidneys, and adipose tissue
List the components located in cytoplasm
– Enzymes – Acyl carrier proteins – Co-factors – Reducing power – Energy (ATP)
List major steps in fatty acid synthesis.
Formation of Acetyl CoA
Conversion of Acetyl CoA to Malonyl CoA
Elongation (addition of carbons)
Desaturation (introduction of double bonds)
What is the rate limiting step of fatty acid synthesis?
Conversion of Acetyl CoA to Malonyl CoA
What is the rate limiting step of fatty acid synthesis catalyzed by?
Acetyl CoA carboxylase (ACC)
How is Acetyl CoA converted to malonyl CoA?
carboxylation
How is ACC regulated?
• Allosteric regulation
• Citrate (+)
• Long chain fatty acids (-)
• Phosphorylation (-)/Dephosphorylation (+)
• Insulin (+)
• Epinephrine (-)
• Glucagon (-)
• Induction/repression
• Gene expression up-regulated by high carbohydrate/low fat diet
• Gene expression down-regulated by high fat/low
carbohydrate diet
Describe Elongation of Fatty Acids.
• Two carbon units from malonyl CoA are
sequentially added to the growing fatty acyl chain to form palmitate (16:0).
• The reactions of fatty acid synthesis occur on the Fatty Acid Synthase Complex.
What is Fatty Acid Synthase (FAS)?
• Large multi-enzyme complex.
• Composed of 2 identical dimers (260 kDa each).
• Each has 7 catalytic activities and an acyl carrier protein (ACP).
• ACP segment has a phosphopantetheine (PP) residue.
• Two dimers arranged in head to tail conformation - PP
of one is aligned with a cysteinyl sulfhydryl group of
another.
List the reactions of fatty acid synthesis.
acetyl ACP to malonyl ACP to acetoacetyl ACP to D-3-hydroxbutyryl ACP to crotonyl ACP to butryryl ACP
How is FAS regulated?
• Allosteric effect (presence of phosphorylated sugars)
• Induction and repression at gene level
– High carbohydrate/low fat diet increases FAS synthesis.
– High fat diet as well as starvation lowers FAS
synthesis.
Describe Eicosanoids.
• Eicosanoids are products generated by the oxidation of 20-carbon fatty acids (arachidonic acid).
• They are signaling molecules and serve as messenger
molecules.
• Short lived molecules, serve as local hormones
• Influence many pathways involved in growth, inflammation, infection, and immunity
What are the four families of eicosanoids?
Prostaglandins, prostacyclins, thromboxanes and
leukotrienes,
What does PGD2 do?
promotion of sleep
What does PGE2 do?
smooth muscle contraction; inducing pain, heat, fever; bronchoconstriction
What does PGE2alpha do?
uterine contraction
What doesTXA2 do?
stimulation of platelet aggregation; vasoconstriction
What does PGI2 do?
inhibition of platelet aggregation; vasodilation; embryo implantation
What does LTB4 do?
leukocyte chemotaxis
Describe mechanism 1 for phospholipid synthesis.
Phosphatidic acid cleaved by phosphatase to form
diacylglycerol (DAG).
DAG reacts with various headgroups to form different
phospholipids.
The headgroups need to be ‘activated’ prior to this
reaction.
Choline headgroup combines with CTP to form CDPcholine (activated).
Phosphocholine (PC) transferred to DAG to form
phosphatidylcholine and CMP is released.
Describe mechanism 2 for phospholipid synthesis.
Phosphatidic acid reacts with CTP to form CDP-DAG.
CDP-DAG reacts with inositol to form PI and CMP.
CDP-DAG may react with glycerol to produce
phosphatidyl glycerol.
The reaction of CDP-DAG with phosphatidyl glycerol
forms diphosphatidyl glycerol (cardiolipin), a component
of the inner mitochondrial membrane.
List the Interconversion between PLs.
PS is formed by exchanging ethanolamine for serine.
PS can be reconverted to PE by decarboxylation.
PE can be methylated to form PC.
Describe Cholesterol
Most abundant sterol (~ 0.05% of total body weight).
Component of membranes and precursor of biologically active compounds:
Bile acids and bile salts
Vitamin D
Steroid hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
Daily intake: ~250 mg (~30-60% absorbed in gut).
Daily production: ~1g, mostly in liver.
Daily excretion: ~5% excreted, ~95% re-absorbed.
Biosynthesis regulated by dietary intake.
How many nobel prizes have been awarded to scientists
who devoted major parts of their careers to cholesterol?
13
Describe the Structure of Cholesterol
Allicyclic compound made of 4 fused rings
Has 27 carbons, 4 rings, 1 double bond between C5
and C6, 2 CH3 at C18 and C19, 1 OH at C3, 8
member hydrocarbon chain attached to C17
List the steps of Cholesterol Biosynthesis
acetyl CoA to mevalonate to squalene to dimethylallylpyrophosphate to lanosterol to cholesterol
What does Oxidosqualene cyclase do?
- holds molecule into place and initiates protonation
Describe HDLs
smallest and dense; high protein and phospholipid content
