Lipids as Fuel (I) Flashcards
Fatty Acids Hydrophobic = \_\_\_\_\_ Hydrophilic = \_\_\_\_\_ SATURATED- No \_\_\_\_\_ UNSATURATED- \_\_\_\_\_ double bonds
methyl/hydrocarbon
carboxyl
double bonds
one or more
Numbering of Fatty Acid Chain
• Carbons are numbered starting with the
_____ group carbon as carbon #1.
• The first carbon after the carboxyl group is the _____ carbon, the last carbon is the _____ carbon.
• The shorthand for numbering is 12:0 or 16:0. This means 12-_____ and 0- _____.
• When fatty acids have double bonds designated as 16:2, 16C with _____ double bonds
carboxyl alpha omega carbons double bonds 2
In Omega-3 FA, the 3rd bond from the omega carbon is _____.
Omega-3 and Omega-6 FA are derived from _____ or acquired in the _____ (e.g. fish).
unsaturated
essential FA
diet
Common Dietary FA
Short Chain- \_\_\_\_\_ carbons ---important in \_\_\_\_\_; mammary glands; sometimes in \_\_\_\_\_, provide quick \_\_\_\_\_ Medium Chain - \_\_\_\_\_ carbons Long Chain - \_\_\_\_\_ carbons
2-3 development oral cavity energy 4-12 12-26
Common Dietary FA
2 essential FA:
- linoleate (DB: _____, _____)
- linolenate (DB: _____, _____, _____)
humans cannot make double bonds past the _____ > precursors to _____ (and eicosatetraenoate) [they are derived from the essential FA]
9-10
12-13
9-10
12-12
15-16
tenth carbon
arachadonate
Phospholipids
• A fatty acyl group is esterified to C#1 and C #2
– C#1 often _____
– C#2 often _____
• There is a _____ at C#3 position to which a water soluble base is esterified.
Properties determined by _____ and _____
saturated unsaturated phosphoryl group headgroup tail
Essential Fatty Acids omega3 versus omega6
linoleic acid (18:2)
alpha-linolenic acid (18:3) must be obtained from the diet.
They are the precursors to _____ and are converted in the body to longer _____.
(omega) refers to the number of the first _____ when counting from the last carbon (_____) in the hydrocarbon chain (this is not the carboxyl carbon)
Alpha-linolenic = _____
Linoleic acid = _____
eicosanoids polyunsaturated FA double bond terminal end omega3 omega6
Omega-3 and Omega-6 fatty acids
The longer chain omega fatty acids, arachidonic acid and EPA are derived from the _____.
They are also provided by the diet in foods such as _____ and are considered _____ fat providing some protection from _____
essential FA
fish
“good”
coronary heart disease
Omega-3 and Omega-6 fatty acids
more beneficial than mono/saturated FA
least healthy FA = _____ (more solid the form of fat)
next = _____
then = _____ (safflower/sunflower/corn/cottonseed)
the healthiest = _____ (fish/flax seed)
saturated
monounsaturated
omega6
omega3
Trans Fats  What are they????? \_\_\_\_\_ fatty acids - double bond in \_\_\_\_\_ configuration. They behave more like \_\_\_\_\_** Man-made-produced from partial \_\_\_\_\_ of vegetable oils
unsaturated
trans
saturated FA
hydrogenation
Trans Fats where are they??
Can be 0 trans fat on label if the level is below _____
2g of trans fat increases risk of CVD by _____
0.5
20%
Fake Fat - Olestra
naturally occuring = triacylglycerol
designed a fake fat with a _____ backbone and eight different FA sidechains
commonly found in _____ products
cannot be _____, can be metabolized by microorganisms and sludge
inhibits the absorption of all _____ (pump products full of lipid soluble vitamins)
Listed as _____ sometimes
sucrose fat-free metabolized fat-soluble vitamins olean
• Olestra is illegal in the _____ and Canada
Positive: Olestra helps remove _____ from the body, as it
apparently binds to _____ in a manner similar to that of _____.
european union
dioxins
dioxins
normal fats
Sources of fatty acids
Dietary fat is in the form of, _____, _____
and _____
Stored fat is in the form of _____ that are cleaved to give free fatty acids
Short and medium chain- less than _____C’s long
Long chain- between _____C’s long
Very-long chain- over _____C’s long
TAG
phospholipids
cholesterol/cholesterol esters
TAG
12
12-22
26
Overview of Digestion
Fats are digested through a series of lipase reactions.
_____ – enzymes that remove fatty acyl chains from backbone structures.
Lingual Lipase -Secreted by cells at the back of the _____. Hydrolyzes medium and short chain fatty acids; those with fewer than _____ carbons. cannot remove FA from _____**
Gastric Lipase-secreted by cells in the _____ hydrolyzes _____ of incoming TAGs.
During the _____ state ingested fat is repackaged and stored as TAG for use during the _____ state
lipases
tongue
12
sucrose
stomach
7-12%
fed
fasting
Overview of digestion
As you swallow you stimulate two processes:
release of bile salts from _____ and release of lipases and bicarbonate from the _____
gallbladder
pancreas
Esterase and PhosphoLipase A2
The product of both reactions is _____
Cholesterol esters commonly found in animal products- they are partially digested by _____. (occurs within the _____)
Phospholipase A2 releases free fatty acid from glycerol backbone of a _____. Cleavage occurs at _____. Formation of _____ and free FA.
free fatty acid
esterase
intestine
phospholipid
c#2
lysophospholipid
Digestion of Dietary Fat Utilizes……
EMULSIFICATION- the process by which dietary fats are suspended in _____ in the aqueous environment by _____. This occurs through the combined action of chewing, vigorous churning in intestines and addition of emulsifying agents.
Cholecystokinin (CCK)- a gut hormone produced by _____ in response to churning stimulates contraction of the _____ and secretion of _____ enzymes and bile.
Pancreatic lipase- produced by _____ cleaves fatty acids from the _____ position of a TAG in the _____
small particles
bile salts/bile acids
intestine
gall bladder
pancreatic
pancreas
1 and 3
small intestine
Digestion of fats depends on repackaging
 TAGs cannot _____ enterocyte membrane therefore they are broken down to _____ and _____
To avoid high levels of free fatty acids inside the enterocytes- the fatty acyl chains are _____ to glycerol to give _____.
The TAGs are packaged into a lipoprotein called a _____
Lipase reactions carried out by _____ in a biliary micelles
cross free FA monoacylglycerol esterified TAGs chylomicrons pancreatic lipase
Formation of biliary micelles
 TAGs containing fatty acids longer than _____ require bile salts/acids for their absorption.
Form a core of _____ in biliary micelles
Micelles are surrounded by amphiphilic _____
Recruit _____ to cleave TAGs.
Biliary micelles increase _____.
12C's lipid bile acids/salts pancreatic lipase surface area
Formation of Biliary Micelles
TAG surrounded by bile salt (_____, derived from cholesteroal); has a OH group and COO- > _____ (take and surround) -> increase the SA
cholate
amphiphilic
Biliary micelles are hydrolyzed by pancreatic lipase
Pancreatic Lipase is inhibited by the _____, the _____ (from the pancreas) relieves this inhibition allowing the pancreatic lipase to cleave the TAGs at the _____ position
bile salts
co-lipase
1 and 3
Absorption of Lipids across the enterocytes
• The newly released fatty acids form small micelles that are absorbed across the brush border membrane.
• Most _____ are reassembled into TAGs.
• The TAG are packaged into large macromolecules called _____.
• Shorter chain fatty acids (less than 12Cs) enter the _____ directly (portal blood).
dietary fats (not olestra)
chylomicrons
circulation
Lipid Metabolic Enzymes as drug targets
side effects of these drugs:
inhibit panc lipases > _____ the amount of dietary fat that circulates, _____ the amount of dietary lipid that is excreted
if we excrete more dietary fat > similar problems with olestra > _____, etc.
decrease
increase
diarrhea
Lipoproteins- transport lipids in circulation
Common Features
Synthesized in the _____ or _____.
Exchange _____ and _____ while in circulation.
Nascent or immature vs. mature forms vs remnants
intestine
liver
lipids
proteins
Lipoproteins - transport lipids in circulation
cylomicrons > _____, _____ lipid surface (makes it easier to access a TAG rich-core)
all other lipid proteins synthesized in _____
once in circulation > become _____
when lipid rich core is depleted/metabolized > becomes a _____
chylomicron are the _____, least _____, TAG-rich, lots of apo proteins
apoB
monolayer
liver
matured
remnant
largest
dense
Chylomicrons- the transport proteins of dietary fat
• Chylomicrons formed in _____ as TAG re-assembles.
• Deliver _____ vitamins
enterocytes
lipid soluble
Chylomicrons- the transport proteins of dietary fat
chylomicrons are only for ingested dietary fat; cannot make an _____
in intestine there’s a _____: B48 (48 kD)
in liver no _____: B100 (100 kD)
REWATCH
will not contain _____, will contain _____
HDL/LDL stop codon stop codon olestra trans-FA
Synthesis and Fate of Chylomicrons
Nascent chylomicrons are synthesized in the _____ and exocytosed through _____
Nascent chylomicrons are Exocytosed through _____
Receive TAG from the _____; receive ApoB-48 from the _____
Enter bloodstream through _____ and mature as they receive _____ and _____ from HDL-another circulating lipoprotein
enterocytes
lymph
lymph
SER
RER
thoracic duct
ApoE Apo-CII
Fat Soluble Vitamins
• _____, derived from food carotenes, benefits; good vision, immune system, reproduction, GI tract, healthy skin. High levels toxic.
- _____, body makes vitamin D from sterol precursor. Benefits; increased absorption of calcium and phosphorus, healthy bone. Excess-kidney stones, weak muscles.
- _____, supplied by diet. Benefits; potent antioxidant, decreases risk of heart disease and cancer.
- _____, supplied in diet and made in body by normal intestinal bacteria and absorbed. Necessary for formation of certain blood clotting proteins.
vitamin A
vitamin D
vitamin E
vitamin K
TAG in Chylomicrons Digested
Apo-CII on the chylomicron activates a _____.
Lipoprotein lipase hydrolyze the TAGs in the chylomicron to provide _____ for the surrounding tissues- usually muscle or adipocytes.
lipoprotein lipase (LPL) FA
Lipoprotein Lipase Activity- tissue specific Km
• Muscle- Km _____ (high affinity) therefore muscle (especially cardiac) is able to hydrolyze and take up fatty acids even when circulating levels of chylomicrons are _____.
• Adipocytes- Km _____ (low affinity) only take up fatty acids from chylomicrons when circulating levels are _____ to be stored for later.
low
low
high
high
Fuel Metabolism
• _____- oxidation of fuels to generate ATP.
• Pathways for fuel oxidation produce _____.
• Acetyl CoA is the precursor for the _____.
• TCA completes the oxidation of fuels to _____.
• Electrons lost during oxidation are transferred to _____ in electron transport chain
• Energy of electron transfer converts ADP and Pi to ATP in _____
respiration Acetyl CoA TCA cycle CO2 O2 oxidative phosphorylation
Critical Definitions
LEO-GER
Loss of Electrons = _____
Gain of Electrons = _____
- Anabolic process-often _____, require energy – build up compounds from component parts
- Catabolic process- often _____, produce energy, break down larger compounds into component parts for fuel
oxidation
reduction
reductive
oxidative
Triacyclglycerols- Storage form of fatty acids
 TAGs are the _____ form of fatty acids Makes up 15% of mass of young adult.
TAG stored in lipid droplets in _____.
Consists of fatty acids esterified to a
glycerol backbone- little _____
These stored fats mobilized in response to the energy needs of tissues. When insulin levels _____ glucagon levels _____.
storage adipocytes hydrophilicity low high
Mobilization of stored fatty acids
Fatty acids stored in adipocytes are mobilized in response to the energy needs of the body by _____ and _____.
Recall from signaling
glucagon activates a _____
glucagon
catecholamines (epinephrine)
GPCR
Mobilization of stored FA
fasting: mobilize stored FA from lipid droplets in adipocytes; glucagon/epinerphrine bind to GPCR > activates _____ > activate _____ > translocates to site of lipid droplet
PKA > also phosphorylates _____; when phos > changes conformation, breaking _____; allows _____ to come in and cleave the TAG into FA
FA mobilized, in BS bound to _____, taken up by various cells for use of energy > _____
PKA
hormone sensitive lipase (HSL)
perilipin
outer shell
HSL
albumin
oxidized
Why do fats provide more energy than glucose?
Hydrocarbon chains are highly _____ compounds, therefore their complete oxidation provides a larger net _____ of energy than carbohydrates.
More than _____ that of carbohydrates.
More is not always better- Because the oxidation of fats: requires \_\_\_\_\_ requires \_\_\_\_\_ Is \_\_\_\_\_ than glucose mobilization some tissues must utilize carbohydrates.
reduced
transformation
twice
energy input
O2
slower
Fundamentals Fat-Facts
• Fatty acid oxidation is the major source of energy for _____ in the body
• Fatty acids are activated as _____- contain high energy bonds.
• Fatty acids stored as TAG provide _____ the energy of an equal weight of glucose and there is no _____ to the amount of fat that may be stored (well almost).
ATP synthesis
acyl Co derivaives
twice
limit
Overview of mitochondrial fatty acid metabolism.
1. Fatty acid binding proteins transport fatty acids across _____
2. Fatty acids are _____
3. Fatty acids transported into mitochondria using _____.
4. β-oxidation generates _____ and _____.
5. Excess Acetyl-CoA generates _____.
plasma membrane activated carnitine NADH FADH2 ketone bodies
Fatty acids must be activated by a CoA before they can be oxidized.
 _____ catalyzes the addition of a CoA derivative onto an Acyl chain
This is a high energy reaction and requires the equivalent of _____ ATPS.
Fatty acyl CoA synthetases are membrane proteins – they reside either in _____ or on intracellular organelles-mostly _____ and _____. _____ for length of the fatty acid.
fatty acyl CoA two plasma membrane peroxisomes mitochondria specificity
Entry into the Mitochondria
• The acyl Co A derivatives cannot cross the mitochondrial membrane- therefore, they are transported transiently attached to a OH of _____.
Carnitine -naturally occurring _____ amino acid derivative, made in the _____ and _____ and derived from meat and dairy products in the diet.
carnitine
kidneys
liver
Entry into Mitochondria
fatty acyl CoA can cross _____ mito membrane; cannot cross into the _____ where beta oxidation occurs
exchanges CoA derivative for a _____ in a reaction catalyzed by CPT1 > FA carnitine and a CoA that is recycled
FA carnitine via a _____ goes into the matrix; becasue it’s NOT a substrate for beta oxidation it’s cleaved, and carnitine is replaced with _____
_____ = PRECURSOR for beta-oxidation
carnitine deficient > cannot get FA into the _____ to be used for oxidation
outer matrix carnitine translocase CoA
FA CoA
matrix
Carnitine Deficiency
• Primary carnitine deficiency
– Incidence in the general population is approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every 40,000 newborns.
– Mutations in the SLC22A5 gene which encodes OCTN2 a _____.
– Signs and symptoms typically appear during _____ or _____ and can include severe brain dysfunction (encephalopathy), a _____ (cardiomyopathy), confusion, vomiting, muscle weakness, and _____ (hypoglycemia). The severity of this condition varies among affected individuals.
cellular carnitine transporter infancy early childhood weakened and enlarged heart low blood sugar
Carnitine Deficiency
primary > mutations in _____
signs and symptoms = lack of _____ after a fast > _____ (the muscle gets larger with not having enough energy)
secondary carnitine deficiency is more _____
anyone on _____; _____ not synthesizing carnitine
cellular carnitine transporter
energy
cardiomyopathia
common
dialysis
HIV/AIDS
β-Oxidation of fatty acids
Location: _____ Stimulated by: High _____,
low _____.
Strategy: Carbons are removed _____ at a time to yield _____
-Each cycle generates 1_____ and 1_____
-AcetylCoA enters _____, and excess converted to _____
mitochondria glucagon insulin two acetyl CoA NADH FADH2 TCA ketone bodies
First reaction in fatty acid oxidation
• Reaction #1
• _____ to produce a double bond between alpha and betaC double bond introduced into a _____
• _____ - electron acceptor.
• Electrons ultimately enter _____ to synthesize 1.5 ATPs/electron pair.
dehydrogenation
carboxylic acid
FAD
OX-PHOS
Second and third reaction in fatty acid oxidation
- Reaction #2. _____
- H2O added to double bond to form an _____
Reaction #3: _____
Dehydrogenase specific for L-isomer. _____ is electron acceptor. _____ ATP molecules generated/per NADH.
isomerization L-isomer dehydrogenation NAD+ 2.5
Fourth reaction in fatty acid oxidation
• Reaction #4.
• Promotes reaction of _____ and free _____. Products are acetyl CoA and AcylCoA that is _____ carbons shorter.
_____, _____, _____ all give you acetyl CoA
ketoacyl CoA
coenzyme A
two
fats
glucose protein
Overview of Energy Formation During Fatty Acid Oxidation
Net Energy Yield from the oxidation of a 16 carbon fatty acid palmitate:
_____ Acetyl Co A (_____ ATPs)
_____ NADH (_____ ATPs)
_____ FADH2 (_____ ATPs)
Total ATP: 108
8 80 7 17.5 7 10.5
Regulation of β-Oxidation
• Point of entry- The carnitine acyl transferase is inhibited by high concentrations of _____(product of _____).
• High charge ratios- The thiolase is allosterically inhibited by _____ and dehydrogenase by high _____.
malonyl CoA
FA synthetis
acetyl CoA
NADH/NAD+
Oxidation of unsaturated fatty acids
Approximately 50 % of the dietary fatty acids are _____, the most common are 18:1 (_____) and the essential fatty acid _____ (18:2)
In oxidation of saturated fatty acids a _____ double bond is created between the second and _____ carbon.
With unsaturated fatty acids their cis double bonds are isomerized to _____. This step does not yield energy thus there is no _____ in net ATP generation
unsaturated
oleate
linoleate
trans
third
trans
increase
Very long chain fatty acids and peroxisomes
Fatty acids with 24 to 26Cs are oxidized in _____. Their peroxisomal oxidation STOPS when the fatty acid reaches a chain length of _____Cs.
1st step is _____ which generates toxic H2O2, this is broken down by a _____
peroxisomes
4 to 6
oxidase
catalase
Very long chain fatty acids and peroxisomes
mitochondria cannot oxidize anything that is approximately over _____ carbons; but diet contains FA that are longer
so what goes on?’
long chain FA are very oxidized in _____ > which contain a long chain FA synthetase; also cleaved _____ carbons at a time just like mitochondria > generate short and medium chain FA with a _____ > these structures then go back to the _____ for beta oxidation
NEVER FULLY _____ IN THE PEROXISOME; only broken down into smaller bits
acetyl CoA cannot cross peroxisomal membrane, attached to _____ so it can exit, goes back to the mito and enters the _____
20 peroxisomes 2 carnitine mitochondria oxidized carnitine TCA cycle
