Lipids: Structure, Absorption, and Metabolism

saturated

fatty acids that do not contain any double bonds

unsaturated

fatty acids that contain one or more double bonds, giving them a bent shape

solid

saturated fatty acids are __________ at room temperature

liquid

unsaturated fatty acids are _____________ at room temperature

omega-3

______________ fatty acids are good for the cardiovascular system; double bond is at the third carbon from the omega carbon

Ex: eicosapentaenoic acid (EPA); docosahexaenoic acid (DHA)

base

add ___________ to the fatty acids to enhance solubility by ionizing them

amphipathic

the majority of lipids, including fatty acids, are ___________________, meaning they have a polar (carboxylic acid) and nonpolar (hydrocarbon) componants

energy

fatty acids are a principle ____________ source in mammals; produce more than carbohydrates when undergoing combustion to carbon dioxide and water because of their highly reduced nature

chain length, unsaturation

fatty acids vary in ___________ ___________ and degree of ______________

higher

the __________ the degree of unsaturation, the lower the melting point of the fatty acid will be

shorter

the ___________ the chain of the fatty acid (lower MW), the lower the melting point will be

cis, trans

_________ unsaturation is healthy and easier to digest and metabolize; _________ unsaturation is not healthy

cell membranes

melting point of fatty acids are key to maintaining the fluidity and functionality of __________________________

TAGs (Triacylglycerols)

the storage form of fatty acids; store energy more efficiently than carbohydrates

carboxylic acid

high concentration of free fatty acids can damage cells, so TAGs "hide" the reactive _____________________ component by forming an ester bond with a glycerol molecule, making it stable and neutral

40

triacylglycerols provide ______% of daily energy requirements for humans

100

triacylglycerols provide ________% of daily energy requirements for hibernating animals and migrating birds

adipose tissue

the major site of accumulation of TAGs in mammals - under the skin and around visceral tissue

membrane lipids

phospholipids, sphingolipids, glycolipids, and steroids are all types of ______________ ____________

phospholipids

common alcohol moieties of __________________: serine, ethanolamine, choline, glycerol, and inositol

sphingolipids

common alcohol moieties of _________________: choline and ethanolamine

nerve

sphingolipids are abundant in __________ cell membranes

phospholipids (examples)

ex: phosphatidylserine; phosphatidylethanolamine

sphingolipids (examples)

ex: sphingosine, sphingomyelin

phosphatidylserine

phosphatidylethanolamine

sphingosine

sphingomyelin

glycolipids

present in all membranes; have sugar molecules (glucose or galactose) instead of phosphorylcholine (in sphingolipids) - sphingosine attached to glucose or galactose

Ex: cerebroside, gangliosides

cerebrosides

steroids

contain a cyclopentanoperhydrophenanthrene nucleus; are membrane constituents, and precursors for hormones and bile acids

cholesterol

micelles

ingested lipids are first emulsified in the stomach by forming _________________

bile salts

in the small intestine, secreded _________________ (ex: glycocholate) further enhance emulsification of lipids

lipase

lipids are hydrolyzed to fatty acids and glycerol by pancreatic ____________; hydrolyze and break the ester bonds by adding water molecule, chopping off one fatty acid at a time

chylomicrons

after being hydrolyzed in the intestinal lumen, the free fatty acids get absorbed through the GI membrane and are reassembled into TAGs and then into ____________________ to travel to the lymph system

catabolism

___________ of triacylglycerols involves

1) mobilization

2) transportation

3) breakdown

glucagon

binds to 7TM receptor on adipocyte which ultimately results in the activation of triacylglycerol lipase via phosphorylation

glycerol

goes to the liver for biotransformation once the TAG is broken down

albumin

plasma protein that carries the free fatty acids from TAG breakdown to a cell in the tissues to be broken down

fatty acyl CoA

the free fatty acid gets activated into ________________ by ATP in the cytosol of the target cell

glyceraldehyde 3-phosphate

glycerol ultimately ends up being metabolized into _______________________ which can enter either glycolysis or gluconeogenesis depending on the needs of the cell

requires ATP and NAD+

5%

____% of energy supply is provided by TAGs - glycerol enters glycolysis or gluconeogenesis

mitochondrial matrix

after the free fatty acids enter their target cell, they undergo activation, conjugation, and transportation into the ______________________

carnitine

the ___________ carrier system brings fatty acyl CoA (activated fatty acids) into the mitochondrial matrix

carnitine acetyltransferase

enzyme that adds and removes carnitine from acyl CoA

acyl carnitine

form of acyl CoA (activated fatty acid) that can cross the inner mitochondrial membrane

beta oxidation

the four-step sequence to degrade saturated fatty acids:

1) oxidation

2) hydration

3) oxidation

4) lysis

oxidation

step one of beta oxidation in which acyl CoA dehydrogenase makes a double bond between carbons 2 and 3, reducing FAD

hydration

second step of beta oxidation in which enoyl hydratase adds water across the double bond

oxidation

third step of beta oxidation in which L-3-hydroxyaceyl CoA dehydrogenase oxidizes the alcohol into a ketone by reducing NADH

thiolysis

fourth step in beta oxidation in which B-ketothiolase breaks the bond between carbons 2 and three, releasing one acetyl CoA molecule

palmitate

16-carbon fatty acid; breakdown generates 106 ATP

10

number of ATP produced for each Acetyl CoA molecule

1.5

number of ATP produced for each NADH molecule

2.5

number of ATP produced for each FADH2 molecule

(#C x 7) - 6

formula for determining how much ATP a fatty acid will generate

isomerase

extra enzyme required for the degredation of mono-unsaturated fatty acids; moves the double bond from C4=C3 to C3=C2

reductase

extra enzyme required for the degredation of multiply-unsaturated fatty acids; first isomerase will move the double bond, and then all other double bonds will be eliminated

propionyl CoA

in the degredation of odd-numbered fatty acids, the final step yields acetyl CoA and ____________________

succinyl CoA

propionyl CoA produced in the degredation of odd-numbered fatty acids gets converted by propionyl-CoA carboxylase (+ biotin carrier) into _________________, which enters the citric acid cycle

FADH2

unsaturated fatty acids do not generate exactly the same amount of ATP as saturated fatty acids because they skip the step of _____________ production (off by about 2.5 ATP)

ketone bodies

C-4 and C-3 compounds that are synthesized in the liver and released to the blood for extrahepatic tissues to use as fuels

citric acid cycle

most acetyl CoA produced by fatty acid degradation enters the _________________________

acetoacetate

formed by the condensation of two acetyl CoA molecules - forms a ketone body

3-hydroxybuterate

acetoacetate can be reduced to form ____________________ (ketone body)

acetone

acetoacetate can emit carbon dioxide to form ______________ (ketone body)

gluconeogenesis

diabetes and fasting are conditions that increase __________________

phosphoenolpyruvate carboxykinase

in type II DM, _________________________ is not suppressed when insulin is secreted so gluconeogenesis continues to generate glucose

oxaloacetate

in type II DM, _____________________ from the citric acid cycle is channeled to gluconeogenesis instead, slowing down the citric acid cycle

acetyl CoA

in type II DM, __________________ is channeled to ketone body formation instead of entering the citric acid cycle because oxaloacetate is being used for gluconeogenesis

ketoacetosis

accumulation of ketone bodies in our system leads to __________________ which may result in coma and death

citrate

in the fed state when there is an excess of Acetyl CoA, it travels from the mitochondria into the cytoplasm by being converted into ______________

pyruvate

when citrate enters the cytoplasm and releases Acetyl CoA for fatty acid synthesis, it becomes oxaloacetate which gets reduced into malate, which then enters back into the mitochondria as _________________

ATP-citrate lyase

enzyme that uses ATP to break citrate back into acetyl CoA and oxaloacetate

8, palmitic acid

the stage I of fatty acid synthesis repeats _____ times to provide the 16C atoms to build one ____________________ molecule

citrate

stage 1 of fatty acid synthesis is the transfer of acetyl CoA from the mitochondria to the cytoplasm as ______________

acetyl CoA

stage II of fatty acid synthesis is the activation of _______________ once in the cytoplasm

acetyl CoA carboxylase (ACC)

key regulatory enzyme in fatty acid synthesis that activates acetyl CoA by converting it to malonyl CoA

malonyl CoA

in fatty acid synthesis (stage II) acetyl CoA gets activated by acetyl CoA carboxylase by converting it into _________________

carnitine shuttle

malonyl CoA is an inhibitor of the __________________________

activators

__________________ of Acetyl CoA Carboxylase are the fed state and high levels of ATP

deactivators

_____________________ of Acetyl CoA Carboxylase are starving/fasting states and a need for energy (low ATP)

fatty acid synthase

Stage III of fatty acid synthesis is the construction of the fatty acid chain, which is catalyzed by the enzyme system collectively known as ___________________________

synthesis

the four reactions of fatty acid _________________:

1) condensation

2) reduction

3) dehydration

4) reduction

repeated until fatty acid is fully assembled

NADP+

fatty acid biosynthesis produces _______________ which goes into the pentose phosphate pathway

7, palmitic acid

repetition of a four-round sequence of fatty acid biosynthesis for _______ rounds generates one molecule of _____________________

Acyl carrier protein (ACP)

part of fatty acid synthase; continuously receives and acetyl group, activates it, and adds it to the growing fatty acid chain

KS

holds the incoming activated acetyl CoA in fatty acid synthesis

beta-ketoacyl-ACP synthase

in fatty acid synthase, condensation occurs at ____________________________ while the remaining 3 reactions occur at ACP after the chain moves back to ACP. The growing chain is then moved back to this enzyme for another round of elongation

thioesterase, palmitate

as soon as the growing fatty acid chain is C16-acyl ACP, the enzyme ______________ cleaves the thioester bond to release free ______________

palmitate

the major product of fatty acid synthase

8, 7, 14, 7

net cost of intermediates involved in synthesis of palmitate:

_____ acetyl CoA

_____ ATP

_____ NADPH

_____ H+

7

synthesis of palmitate requires _____ ATP

1

____ NADPH is generated for each acetyl CoA transferred as citrate

6

____ NADPH are generated by the PPP

longer-chain fatty acids

___________________ are synthesized by addition of more malonyl CoA to units of C-16 chains

ER (endoplasmic reticulum)

enzymes on the surface of the _____________________ catalyze the reactions of introducing double bonds in saturated fatty acids

linoleate and linolenate

essential fatty acids because mammals cannot introduce double bonds in fatty acids beyond C-9; therefore they must be supplied by the diet

eicosanoids

C-20 unsaturated fatty acids derived from the cell membrane component arachidonic acid (20:4); short-lived local hormones that play a pivotal role in inflammation, blood flow, ion transport, and allergy

Ex: prostaglandins and leukotrienes