Fatty Acid Synthesis Flashcards
what is the main source of fuel stores in the body?
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
what are the sources of fuel in the body?
- traicylglycerols
- protein
- glycogen
- glycose
what is key for fats high energy storage capacity?
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
where are the three places fatty acids and triglycerides come from?
- diet
- mobilized from adipocytes
- TAG synthesis in liver (de novo)
what kind of fats do we get from our diet?
triacylglycerols (TAG) aka triglycerides (TG) = interchangeable, mean the same thing
energy is extracted from this molecule through beta-oxidation
where are fats in the form of TAGs stored in the body?
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
how do dietary fats make it from the stomach to adipose cells?
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%)
what are the steps that it takes to get TAGs from your diet to adipose cells?
- 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
- 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
- FFA and MAG pass through membrane of the mucosal cells
- once MAG and FFA are inside the musical cells, TAG is reassembled
- mucosal cell will provide other lipids and proteins to package TAGs into particles called chylomicrons
- chylomicrons are secreted by mucosal cells into lymphatics where they enter the blood circulation and ultimately reach the adipose tissues
how do TAGs in chylomicrons make it into adipose tissues?
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
how do chylomicrons deliver TAG cargo to adipose?
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!!!
where is LPL located?
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
what stimulates LPL activity?
LPL activity is stimulated by insulin!!!!
when insulin is high after a meal, this is when storage of TAGs is promoted
what happens in energy poor situations?
adipocyte lipid droplet stores are mobilized
when are fats mobilized from adipocytes? what’s the process that does it?
- high energy demands like exercise or nutritional deprivation due to starving or fasting
or
- 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
what is beta oxidation?
the process of deriving energy from stored fats
how are fats mobilized from adipocytes?
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
- hormone sensitive lipase (HS Lipase): takes off 2nd FA chain
- 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
what are serum albumin carriers?
they’re the proteins that shuttle FFA in circulation after they’ve been broken down from adipose tissue
what are the two things that regulate TGA mobilization in adipose?
- 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
- ENZYME regulated
catecholamines like epinephrine that are released in times of high stress
what’s the difference between FA synthesis (anabolic) and FA beta-oxidation (degradation)?
look at slide 22 in LM 9.2
what is the precursor for FA synthesis?
acetyl-CoA
what’s the overview of FA synthesis?
- acetyl CoA is activated by carboxylation to form malonyl CoA
- decarboxylation drives sequential condensation reactions (chain building)
- fatty acid synthase generates palmitate
- other enzymes extend and desaturate palmitate
what are the two phases of FA synthesis? what is the overview of what happens during them?
- activation:
acetyl CoA is carboxylated to malonyl CoA which is the first committed step of FA synthesis = it’s IRREVERSIBLE - elongation
Fatty acid synthase reactions build the 16 carbon hydrocarbon chain of palmitate through a repeated related series of reactions
what are the chemical reactions happening in each step of FA synthesis vs. b-oxidation?
aka reduction, hydration, etc.
FA synthesis:
- condensation with CO2 loss
- reduction
- dehydration
- reduction
B-oxidation:
- oxidation
- hydration
- oxidation
- cleavage-thiolysis
they’re backwards of each other!
which enzymes are linked to FA synthesis?
reductases
dehydratase
