lecture 8 Flashcards
fatty acids
hydrocarbon chin with carboxyl group, can have a double bond that introduces a kink
most abundant dietary lipids, triglycerides
found in both animal and plant foods
essential fatty acids
linoleic and linolenic acid, found in most vegetables, must be ingested
fatty deposits in adipose tissues provide
-a protective cushion around body organs
-an insulating layer beneath the skin
-an easy-to-store concentrated source of energy
Dietary fats
-help body to absorb vitamins
-are a major energy fuel hepatocytes and skeletal muscle
-Are a component of myelin sheaths and all cell membranes
prostaglandins function in
-smooth muscle contraction
-control of blood pressure
-inflammation
cholesterol
stabilizes membranes and is a precursor of bile salts and steroid hormones
the liver
-Synthesizes lipoproteins for transport of cholesterol and fats
-Makes tissue factor, a clotting factor
-Synthesizes cholesterol from acetyl CoA
-Uses cholesterol to form bile salts
certain endocrine organs
use cholesterol to synthesize steroid hormones
sphingolipids
often found in neural coverings
ester bonds
how fatty acids are linked
both glycerol and fatty acids
are metabolized in distinct ways
cells obtain fatty acid fuel from 3 sources
-fats consumed in the diet
-fats stored in cells as lipid droplets
-fats synthesized in one organ for export to another
most products of fat metabolism
are transported in lymph as chylomicrons
cytosol
glycolysis
pentose phosphate pathway
fatty acid synthesis
mitochondrial complex
citric acid cycle
oxidative phosphorylation
ketone body formation
beta oxidation of fatty acids
interplay of both cytoplasm and mitochondria
gluconeogenesis
urea synthesis
lipids in chylomicrons are
hydrolyzed by plasma enzymes and absorbed by cells
only neutral fats
are routinely oxidized for energy
catabolism of fats involves two seperate pathways
glycerol pathway
fatty acid pathway
major component of chylomicron
triglycerides
phospholipid surface
polar headgroups face outward
trglycerols are found in the interior
make up >80% of the mass
Apolipoproteins on exterior
serve as signals for chylomicron uptake & metabolism
Glycerol is converted to glyceraldehyde 3-phosphate (GAP)
-GAP is ultimately converted into acetyl CoA
-Acetyl CoA enters the Krebs cycle
Fatty acids undergo beta oxidation which produces
-Two-carbon acetic acid fragments, which enter the Krebs cycle
-Reduced coenzymes, which enter the electron transport chain
lipids hydrolyze triacylglycerols
-free fatty acids
-glycerol
fatty acids form acetyl coa
-citric acid cycle
glycerol phosphorylated
oxidized to DHAP
converted to GAP
GAP enters glycolysis
payoff phase
3 steps are required for fatty acid breakdown
- Lipids must be mobilized: triglycerols degraded into fatty acids & glycerol. Subsequently released from adipose tissue into energy-requiring tissues.
- Fatty acids must be activated and transported into mitochondria for degradation.
- Fatty acids broken down, step-by-step, into acetyl-CoA which is fed into the Krebs/TCA cycle.
mobilization of triglycerols
triglycerols degrades into fatty acids and glycerol. Subsequently released from adipose tissue into energy requiring tissue
low blood glucose
stimulates glucagon release
Glucagon activates receptor-G protein-adenylate cyclase system
activates hormone-sensitive lipases (HSL)
PKA phosphorylation of perilipin permits
access of HSL to triglycerols in fat droplets
Fatty acids released from adipocyte into bloodstream
bind to serum proteins, transported to other cells (i.e., myocytes) for use as energy source
hormone sensitive lipase
responsive to glucagon and insulin
activation of fatty acids
and transportation into mitochondria for degradation
carnitine is converted to acyl carnitine
acyl carnitine is brought into cell where it is converted back to carnitine
stage 1 of fatty acid oxidation
beta oxidation of fatty acids
stage 2
acetyl CoA oxidized to CO2
stage 3
electrons transferred from NADH/FADH2 to ETC for ATP synthesis
degradation of even-numbered saturated fatty acids into acetyl-CoA
respective sequence of:
-oxidation
-hydration
-oxidation
-thiolysis
trans delta 2 enoyl CoA
very important intermediate for even and odd degradation
oxidation of palmitate
produces 8 molecules of acetyl CoA
b-Oxidation of Monounsaturated Fatty Acids
requires 1 additional enzyme:enoyl-CoA isomerase and loses 2 ATP per double bond
ß-Oxidation of Polyunsaturated Fatty Acids
Requires 1 additional enzyme (in addition to the additional enoyl CoA isomerase required for monounsaturated): 2,4-dienoyl-CoA reductase
lose 3 ATP per additional double bond
ß-Oxidation of Odd-Chain Length Fatty Acids
Same as oxidation of saturated FA’s but end with 3C
converted to succinyl CoA
excess dietary glycerol and fatty acids undergo lipogenesis to form
triglycerides
glucose easily converts to fats since acetyl coa is
An intermediate in glucose catabolism
The starting molecule for the synthesis of fatty acids
lipolysis
the breakdown of stored fat, is essentially lipogenesis in reverse
Oxaloacetate
necessary for the complete oxidation of fat
otherwise ketogenesis begins
When diet provides carbohydrate fuel
oxidation of fats is unnecessary
Two enzymes key for coordinated regulation
1) acetyl-CoA carboxylase (ACC)
2) carnitine acyl transferase I
ACC
first enzyme in FA synthesis pathway
Carnitine acyl transferase I
regulates transport of FA into mitochondrial matrix for b-oxidation
high carb meal
stimulates insulin release
Insulin-dependent protein phosphatase
dephosphorylates ACC (activates enzyme)
ACC catalyzes
formation of malonyl-CoA (first intermediate in FA synthesis)
Malonyl-CoA inhibits
carnitine acyltransferase I (prevents FA entry into mitochondrial matrix)
When blood glucose drops between meals
Glucagon release activates PKA
PKA phosphorylates ACC (inactivates enzyme)
Malonyl-CoA levels decrease (FA entry into mitochondria is restored)
FA oxidation in mitochondria major form of fuel
Glucagon also stimulates mobilization of FA from adipose tissue, FA available from bloodstream
