Lipids as Fuel (I) Flashcards

1
Q
Fatty Acids
Hydrophobic = \_\_\_\_\_
Hydrophilic = \_\_\_\_\_
SATURATED- No \_\_\_\_\_ 
UNSATURATED- \_\_\_\_\_ double bonds
A

methyl/hydrocarbon
carboxyl
double bonds
one or more

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2
Q

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

A
carboxyl
alpha
omega
carbons
double bonds
2
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3
Q

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).

A

unsaturated
essential FA
diet

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4
Q

Common Dietary FA

Short Chain- \_\_\_\_\_ carbons 
---important in \_\_\_\_\_; mammary glands; sometimes in \_\_\_\_\_, provide quick \_\_\_\_\_
Medium Chain - \_\_\_\_\_ carbons
Long Chain -
\_\_\_\_\_ carbons
A
2-3
development
oral cavity
energy
4-12
12-26
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5
Q

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]

A

9-10
12-13

9-10
12-12
15-16

tenth carbon
arachadonate

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6
Q

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 _____

A
saturated
unsaturated
phosphoryl group
headgroup
tail
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7
Q

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 = _____

A
eicosanoids
polyunsaturated FA
double bond
terminal end
omega3
omega6
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8
Q

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 _____

A

essential FA
fish
“good”
coronary heart disease

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9
Q

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)

A

saturated
monounsaturated
omega6
omega3

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10
Q
Trans Fats
 What are they?????
 \_\_\_\_\_ fatty acids - double bond in \_\_\_\_\_
configuration.
 They behave more like \_\_\_\_\_**
Man-made-produced from partial \_\_\_\_\_ of
vegetable oils
A

unsaturated
trans

saturated FA

hydrogenation

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11
Q

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 _____

A

0.5

20%

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12
Q

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

A
sucrose
fat-free
metabolized
fat-soluble vitamins
olean
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13
Q

• 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 _____.

A

european union
dioxins
dioxins
normal fats

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14
Q

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

A

TAG
phospholipids
cholesterol/cholesterol esters

TAG
12
12-22
26

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15
Q

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

A

lipases
tongue
12
sucrose

stomach
7-12%
fed

fasting

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16
Q

Overview of digestion

As you swallow you stimulate two processes:

release of bile salts from _____ and release of lipases and bicarbonate from the _____

A

gallbladder

pancreas

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17
Q

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.

A

free fatty acid
esterase
intestine

phospholipid
c#2
lysophospholipid

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18
Q

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 _____

A

small particles
bile salts/bile acids

intestine
gall bladder
pancreatic

pancreas
1 and 3
small intestine

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19
Q

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

A
cross
free FA
monoacylglycerol
esterified
TAGs
chylomicrons
pancreatic lipase
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20
Q

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 _____.

A
12C's
lipid
bile acids/salts
pancreatic lipase
surface area
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21
Q

Formation of Biliary Micelles

TAG surrounded by bile salt (_____, derived from cholesteroal); has a OH group and COO- > _____ (take and surround) -> increase the SA

A

cholate

amphiphilic

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22
Q

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

A

bile salts
co-lipase
1 and 3

23
Q

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).

A

dietary fats (not olestra)
chylomicrons
circulation

24
Q

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.

A

decrease
increase
diarrhea

25
Q

Lipoproteins- transport lipids in circulation

Common Features
 Synthesized in the _____ or _____.
 Exchange _____ and _____ while in circulation.
 Nascent or immature vs. mature forms vs remnants

A

intestine
liver
lipids
proteins

26
Q

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

A

apoB
monolayer

liver

matured

remnant
largest
dense

27
Q

Chylomicrons- the transport proteins of dietary fat

• Chylomicrons formed in _____ as TAG re-assembles.
• Deliver _____ vitamins

A

enterocytes

lipid soluble

28
Q

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 _____

A
HDL/LDL
stop codon
stop codon
olestra
trans-FA
29
Q

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

A

enterocytes
lymph

lymph

SER
RER

thoracic duct
ApoE Apo-CII

30
Q

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.
A

vitamin A
vitamin D
vitamin E
vitamin K

31
Q

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.

A
lipoprotein lipase (LPL)
FA
32
Q

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.

A

low
low
high
high

33
Q

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 _____

A
respiration
Acetyl CoA
TCA cycle
CO2
O2
oxidative phosphorylation
34
Q

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
A

oxidation
reduction

reductive
oxidative

35
Q

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 _____.

A
storage
adipocytes
hydrophilicity
low
high
36
Q

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 _____

A

glucagon
catecholamines (epinephrine)

GPCR

37
Q

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 > _____

A

PKA
hormone sensitive lipase (HSL)

perilipin
outer shell
HSL

albumin
oxidized

38
Q

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.
A

reduced
transformation
twice

energy input
O2
slower

39
Q

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).

A

ATP synthesis
acyl Co derivaives

twice
limit

40
Q

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 _____.

A
plasma membrane
activated
carnitine
NADH
FADH2
ketone bodies
41
Q

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.

A
fatty acyl CoA
two
plasma membrane
peroxisomes
mitochondria
specificity
42
Q

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.

A

carnitine
kidneys
liver

43
Q

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

A
outer
matrix
carnitine
translocase
CoA

FA CoA
matrix

44
Q

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.

A
cellular carnitine
transporter
infancy
early childhood
weakened and enlarged heart
low blood sugar
45
Q

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

A

cellular carnitine transporter

energy
cardiomyopathia

common

dialysis
HIV/AIDS

46
Q

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 _____

A
mitochondria
glucagon
insulin
two
acetyl CoA
NADH
FADH2
TCA
ketone bodies
47
Q

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.

A

dehydrogenation
carboxylic acid
FAD
OX-PHOS

48
Q

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.

A
isomerization
L-isomer
dehydrogenation
NAD+
2.5
49
Q

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

A

ketoacyl CoA
coenzyme A

two

fats
glucose protein

50
Q

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

A
8
80
7
17.5
7
10.5
51
Q

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 _____.

A

malonyl CoA
FA synthetis
acetyl CoA
NADH/NAD+

52
Q

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

A

unsaturated
oleate
linoleate

trans
third

trans
increase

53
Q

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 _____

A

peroxisomes
4 to 6
oxidase
catalase

54
Q

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 _____

A
20
peroxisomes
2
carnitine
mitochondria
oxidized
carnitine
TCA cycle