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HMBP Week 2 > Fatty Acid Synthesis > Flashcards

Fatty Acid Synthesis Flashcards

1
Q

what is the main source of fuel stores in the body?

A

triacylglycerols = 100,000 kcal of stores energy

glucose and glycogen can only fuel a human for short duration of time

protein can also be used in times of extreme fasting

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2
Q

what are the sources of fuel in the body?

A
  1. traicylglycerols
  2. protein
  3. glycogen
  4. glycose
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3
Q

what is key for fats high energy storage capacity?

A

it’s anhydrous!

so gram for gram it contains 9kcal/g if it’s completely oxidized

glycogen is a hydrated molecule, it doesn’t exist in the body in a dry form, so after accounting for water weight, wet glycogen like in your liver only gives 1.32 kcal/gram

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4
Q

where are the three places fatty acids and triglycerides come from?

A
  1. diet
  2. mobilized from adipocytes
  3. TAG synthesis in liver (de novo)
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5
Q

what kind of fats do we get from our diet?

A

triacylglycerols (TAG) aka triglycerides (TG) = interchangeable, mean the same thing

energy is extracted from this molecule through beta-oxidation

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6
Q

where are fats in the form of TAGs stored in the body?

A

adipocytes!

  • cells hold up to 90% TAG by weight: most of the cell is filled with the TAG!
  • TAG droplets coalesce in large cytoplasmic globules
  • the cell nucleus and cytoplasm are pushed to a narrow rim around the lipid drop; they get squished to the edge
  • hypertrophy of adipocytes occurs in obesity; dieting shrinks lipid droplets
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7
Q

how do dietary fats make it from the stomach to adipose cells?

A

digestion of fats is mostly in the small intestine

a small amount of TAGs are digested in the stomach by lingual lipase secreted by lingual glands in the mouth and swallowed with the saliva (<10%)

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8
Q

what are the steps that it takes to get TAGs from your diet to adipose cells?

A
  1. TAG in what you are will mix with bile slats in the lumen of the small intestine which will emulsify the fat to help make the lipid more accessible for enzymes called ligases that will help digest the lipids
  2. pancreatic lipases work on TAGS but don’t completely break them down - they just release 2/3 FAs from the glycerol backbone which leaves a monoacyl glycerol (MAG) - this happens because TAG can’t cross mucosal cell membrane lining the small intestine
  3. FFA and MAG pass through membrane of the mucosal cells
  4. once MAG and FFA are inside the musical cells, TAG is reassembled
  5. mucosal cell will provide other lipids and proteins to package TAGs into particles called chylomicrons
  6. chylomicrons are secreted by mucosal cells into lymphatics where they enter the blood circulation and ultimately reach the adipose tissues
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9
Q

how do TAGs in chylomicrons make it into adipose tissues?

A

chylomicrons can’t just drop their TAG cargo at the adipose tissue

lipoprotein lipase (LPL) on the local capillary endothelial cells must participate to load up a lipid droplet in the adipose with fresh TAG

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10
Q

how do chylomicrons deliver TAG cargo to adipose?

A

TAG from the dietary source in chylomicrons and TAG from particles near the adipose called VLDL from the liver

adipocytes don’t allow TAG to simply cross a cell membrane so lipoprotein lipase (LPL) that’s localized on endothelial membranes will cleave the TAG

TAG gets broken into 2FFA and monacylglycerol backbone again and then they’ll get reassembled again

LPL is stimulated by insulin!!!

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11
Q

where is LPL located?

A

LPL = lipoprotein lipase which breaks TAG down so it can get into adipocytes

located on the luminal surface of the capillary epithelial cells - capillaries that feed the adipocytes are the cells that have the highest concentration of LPL enzyme

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12
Q

what stimulates LPL activity?

A

LPL activity is stimulated by insulin!!!!

when insulin is high after a meal, this is when storage of TAGs is promoted

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13
Q

what happens in energy poor situations?

A

adipocyte lipid droplet stores are mobilized

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14
Q

when are fats mobilized from adipocytes? what’s the process that does it?

A
  1. high energy demands like exercise or nutritional deprivation due to starving or fasting

or

  1. when carbohydrates aren’t being used in an efficient manner like during diabetes where glucose isn’t mobilized in your cell

in these situations, beta oxidation of fat is used for our primary sources of energy; TAGs stored in lipid droplets in adipose are released and exported to tissues where beta oxidation is taking place

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15
Q

what is beta oxidation?

A

the process of deriving energy from stored fats

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16
Q

how are fats mobilized from adipocytes?

A

breakdown TAG in the adipose cell since it can’t shuttle across the membrane - this is a stepwise process with 3 enzymes:
1. adipose triglyceride lipase (ATGL): takes off 1st FA chain

  1. hormone sensitive lipase (HS Lipase): takes off 2nd FA chain
  2. monoglyceride lipase (ML): takes off last FA from glycerol backbone

now you have glycerol backbone and THREE FFA chains that get exported into circulation

FFA is available for beta oxidation in muscles and glycerol will hit the liver where it can be used productively

17
Q

what are serum albumin carriers?

A

they’re the proteins that shuttle FFA in circulation after they’ve been broken down from adipose tissue

18
Q

what are the two things that regulate TGA mobilization in adipose?

A
  1. HORMONALLY regulated:

the hormones controlling this process are glucagon and insulin - glucagon is stimulated by a drop in glucose levels and insulin is stimulated by an increase in glucose

TAG mobilization is stimulated by glucagon because it means glucose levels are low and we’re going to need to utilize fats for energy

  1. ENZYME regulated

catecholamines like epinephrine that are released in times of high stress

19
Q

what’s the difference between FA synthesis (anabolic) and FA beta-oxidation (degradation)?

A

look at slide 22 in LM 9.2

20
Q

what is the precursor for FA synthesis?

A

acetyl-CoA

21
Q

what’s the overview of FA synthesis?

A
  1. acetyl CoA is activated by carboxylation to form malonyl CoA
  2. decarboxylation drives sequential condensation reactions (chain building)
  3. fatty acid synthase generates palmitate
  4. other enzymes extend and desaturate palmitate
22
Q

what are the two phases of FA synthesis? what is the overview of what happens during them?

A
  1. activation:
    acetyl CoA is carboxylated to malonyl CoA which is the first committed step of FA synthesis = it’s IRREVERSIBLE
  2. elongation
    Fatty acid synthase reactions build the 16 carbon hydrocarbon chain of palmitate through a repeated related series of reactions
23
Q

what are the chemical reactions happening in each step of FA synthesis vs. b-oxidation?

aka reduction, hydration, etc.

A

FA synthesis:

  1. condensation with CO2 loss
  2. reduction
  3. dehydration
  4. reduction

B-oxidation:

  1. oxidation
  2. hydration
  3. oxidation
  4. cleavage-thiolysis

they’re backwards of each other!

24
Q

which enzymes are linked to FA synthesis?

A

reductases

dehydratase

25
Q

which enzymes are linked to B-oxidation?

A

thiolase
oxidase
hydratases

26
Q

what happens in the activation step of FA synthesis?

A

enzyme: acetyl CoA carboxylase (ACC Carboxylase)

the objective of activation is to generate malonyl CoA (3 carbons) to use in FA elongation

the assumption is that you have 2 extra carbons from acetyl CoA that came from the TCA cycle if you’re in an energy rich environment

****so what you NEED is ATP, acetyl CoA, and CO2 (exists as HCO3- in the body) and what you MAKE is malonyl CoA, H2O and ADP

27
Q

what does acetyl CoA carboxylase have that helps it during FA synthesis activation?

A

it have a biotin prosthetic group

biotin serves as an intermediate CO2 carrier

28
Q

what happens in the elongation step of FA synthesis?

A

enzyme: fatty acid synthase

objective of elongation is to build a hydrocarbon FA chain, 2 carbons at a time

you NEED malonyl CoA, acetyl CoA, NADPH and H+ and what you MAKE is palmitate, CO2, NADP+, CoA and H2O

29
Q

what are the characteristics of fatty acid synthase?

A

cytoplasmic enzyme with acyl carrier protein (ACP) as a cofactor

multiple enzymatic activities in a large protein complex

uses malonyl-CoA to build palmitate, 2 carbons at a time while simultaneously losing carboxyl group

the 2 carbon units are those that were originally derived from acetyl CoA when malonyl CoA was formed

30
Q

what is the first reaction that get things started during FA elongation?

A

objective is to get the ACP group tacked onto the acetyl CoA &&&& swap out ACP for the ketosynthase group from the FA synthase enzyme complex

enzyme: acetyl transacylase

you need acetyl CoA and ACP and you make an acetyl group tacked onto the KS subunit of the FA synthase complex and a free ACP

31
Q

what is the second reaction that get things started during FA elongation?

A

objective is to bind a malonyl group from malonyl CoA from the activation step to the free acyl carrier protein (ACP) subunit of FA synthase enzyme

enzyme: malonyl transacylase

you need malonyl CoA and ACP and you make malonyl-ACP and free CoA

32
Q

what’s the first real reaction in FA elongation?

A

condensation/decarboxylation

combines 2-carbon acetyl group acetyl-KS with 2 carbons from malonyl group, malonyl-ACP and removes COO- from malonyl-ACP

enzyme: acyl-malonyl-ACP condensing enzyme

acetyl-KS + malonyl-ACP –> acetoacetyl-ACP + CO2 + KS

33
Q

what’s the second real reaction in FA elongation?

A

reduction

removes a keto-group from acetoacetyl-ACP

enzyme: beta-ketoacyl-ACP reductase

acetoacetyl-ACP + NADP + H+ –> D-3-hydroxybutyrl-ACP + NADP+

34
Q

what’s the third real reaction in FA elongation?

A

dehydration

remove water from D-3-hydroxybutyryl-ACP

enzyme: 3-hydroxyacyl-ACP dehydrates

D-3-hydroxybutyryl-ACP –> crotonyl-ACP + H2O

35
Q

what’s the second fourth reaction in FA elongation?

A

reduction

remove the double bond in the 4 carbon hydrocarbon chain - moves over to KS subunit for next 2C addition in elongation via the original malonyl-ACP condensation reaction to get a 6C chain –> this continues until you get to 16C

enzyme: enoyl-ACP reductase

crotonyl-ACP + NADHPH + H+ –> butyryl-ACP

36
Q

what’s the final reaction in FA synthesis?

A

16C palmityl-ACP needs to lose that ACP to be a useful 16C palmitate FA chain to incorporate into a TAG

enzyme: thioesterase

palmityl-ACP + H2O –> 16C palmitate with a carboxyl group + ACP

HMBP Week 2 (6 decks)

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