Chapter 17 Flashcards
Four major functions of lipids
structural components
energy reserves
vitamins
hormones
Summary of how lipids are transported
from the intestine as chylomicrons to the liver and other tissues
other tissues to liver as HDL
leaves the liver as VLDL that changes into LDL
LDL then moves to other tissues and the liver
Triaglycerols
glycerol bonded to three fatty acids
main storage form of fat
The release of fatty acids from triacylglycerols and phosphoacylglycerols is catalyzed by
lipases
the breakdown of a triacylglycerol creates
three fatty acids
Phospholipases D’s
destroy cell membranes
The release of fatty acids in adipocytes is under
hormonal control- epinephrine
cyclic AMP begins a kinase cascade that leads to phosphorylation and activation of the lipases
fatty acids are released and can then be oxidized to produce ATP in the mitochondria
Fatty acids are oxidized via _____ to produce ____
beta- oxidation
acetyl-CoA
Beta oxidation takes place in the
mitochondria
Acetyl CoA is used to generate energy via the
citric acid cycle
electron transport chain
Fatty acid activation
two steps catalyzed by acyl-CoA synthetase
A repeated sequence of four reaction that occur in the mitochondrial matrix
Beta oxidation of fatty acids
Goals of beta oxidation
- create a carbonyl group on the beta carbon by shortening the acyl group by two carbons
- removed as acetyl-CoA - generate energy by producing the reduced electron carriers FADH2 and NADH
The first reaction of beta oxidation
electron transfer reactions
The second reaction of Beta oxidation
addition of water
The third reaction of beta oxidation
NAD+ cofactor
fourth reaction of beta oxidation
release of acetyl-CoA
Beta oxidation- Electron transfer reactions are catalyzed by
acyl-CoA dehydrogenase
Beta oxidation- addition of water is catalyzed by
hydratase
Beta oxidation- NAD+ cofactor is catalyzed by
another dehydrogenase
Beta oxidation- release of acetyl-CoA is catalyzed by
thiolase
Energy yields from beta oxidation
1 NADH, 1 FADH2 and 1 acetyl-CoA
NADH and FADH2 generate ATP via electron transport chain and ATP synthase
acetyl-CoA enter the citric acid cycle to generate 1 FADH2, 3 NADH, 1 GTP
Total ATP 120
Fats are more ______ than sugars and amino acids
reduced
Beta oxidation of fatty acids steps
- oxidation of beta carbon generated FADH2
- Hydration of beta carbon generates -OH groups
- oxidation of beta carbon generates NADH and a carbonyl group
- cleavage between the alpha and beta carbons and formation of acetyl-CoA
5 further cycles
Fatty acyl-CoA is shortened by 2 carbons from the
carbonyl end
Beta oxidation repeats until
there are just two carbons left
Fatty acids with ___ double bonds pose a problem for enzymes in beta oxidation
cis
Cis double bonds are turned into trans double bonds by what enzyme
isomerase
Why do unsaturated fatty acids yield less free energy than saturated fatty acids
creates fewer FADH2 due to having to use an isomerase to change a cis bond to a trans bond
ODD chain length fatty acids beta oxidation difference
occurs until three carbons are left
propionyl-CoA created at the end
in order to enter the citric acid cycle propionyl-CoA (created by odd numbered chain) must go through
carboxylation to methyl-malony-CoA and rearrangement to succinyl-CoA
Beta oxidation of fatty acids produces metabolic water how?
FADH2 and NADH produce water in the electron transport chain
Peroxisomes
enclosed by a single membrane and contain a variety of degradative and biosynthetic enzymes
How does fatty acid oxidation in peroxisomes differ from that in mitochondria
enoyl-CoA product of the reaction is identical to the product of the mitochondrial acyl-CoA dehydrogenase reaction
What happens if we don’t consume carbs
no glycolysis
rely on fatty acids for acetyl-CoA
Liver does gluconeogenesis making glucose
TCA stops because acetyl-CoA directed to make glucose for the brain
In long fasts and starvation oxaloacetate is
consumed to make glucose by the gluconeogenic pathway so acetyl CoA accumulates
Increased acetyl CoA makes
acetoacetate
beta hydroxybutyrate
acetone
All of these are ketone bodies
Ketone bodies are made
in the liver mitochondria
Production of ketone bodies
two acetyl-CoA are condensed to acetoacetyl-CoA
Another condensation with acetyl-CoA produces hydroxyl-alpha-methylglutaryl-CoA
HMG-CoA lyase releases acetyl-CoA to produce acetoacetate
Acetoacetate is either decarboxylated to acetone or reduced to alpha hydroxybutyrate
Ketone bodies are used by the
brain as a fuel source during starvation
Why is an excess of ketone bodies bad?
are acidic and can lower the pH of the blood
Ketoacidosis
- increased thirst, secretion of H+ into the urine
- symptom of untreated diabetes (type 1)
Anabolism of fatty acids happens in the
cytosol
Anabolism of fatty acids is/is not a simple reversal of beta oxidation
NOT
First step of anabolism is
exporting acetyl-CoA from the matrix to the cytoplasm via a citrate intermediate
Formation of the main precursor to fatty acid synthesis of _____ is from the carboxylation of acetyl-CoA
malonyl-CoA
Formation of malonyl-CoA is catalyzed by
acetyl-CoA carboxylase (ACCase) complex
ACCase requires
biotin, Mn2+, and ATP
Fatty acid synthesis priming groups
- two carbon acetyl group that will be lengthened is transferred from CoA to a Cys side chain of fatty acid synthesis
- malonyl group will donate an acetyl group to the growing fatty acyl chain is transferred from CoA to the ACP domain of the enzyme
Subsequent steps of fatty acid synthesis
- condensation reaction- malonyl group is decarboxylated and the resulting two-carbon fragment attacks the acetyl group to form a four-carbon product
- 3-ketoacyl product of step 3 is reduced
- dehydration introduces a 2,3 double bond
- second NADPH dependent reduction completes the conversion of the condensation product to an acyl group
- acyl group is transferred from ACP to enzymes Cys group
another malonyl group is loaded onto the free ACP
ready for another condensation reaction
free fatty acids are mostly found
incorporated within triacylglycerols and phosphoacylglycerols
synthesis of these compound occurs in the endoplasmic reticulum of liver or fat cells
main point of regulatory control for fatty acid metabolism
ACCase
phospholipid synthesis
- ATP phosphorylates the OH group of ethanolamine or choline
- phosphoryl group attacks CTP to form CDP-ethanolamine or CDP-choline. PPi product is hydrolyzed
- the C3 OH group of diacylglycerol displaces CMP to generate the glycerophospholipid
Phosphatidylserine synthesis
head-group exchange reaction
Phosphatidylinositol synthesis
- phosphatidase attacks CTP to form CDP- diacylglycerol
- an inositol group displaces CMP to produce phosphatidylinositol
Every carbon of cholesterol is derived from
acetyl-CoA carbons
Cholesterol is stored as
an ester
changed using acyl-CoA (cholesterol acyltransferase)
Cholesterol synthesis inhibitors
Lipitor
lovastatin
simvastatin
The body coordinates cholesterol production and transport among tissues
SREBP regulatory system
Steroid hormones are synthesized from
cholesterol
