Lipid Metabolism

chylomicrons are transported from the enterocyte to

lymphatics

the lymphatic system empties into

the subclavian vein

the subclavian vein brings

chylomicrons to the liver

in the liver, some chylomicrons are repackaged as 

other lipoproteins that are then circulated to other tissues 

chylomicrons are

a form of lipoproteins circulating in the blood

lipoproteins are classified by their densitiy which is equal to

protein:lipid ration

more protein in lipoproteins means

increased density

more lipid in lipoproteins means 

decreased density 

four classes of lipoproteins are

chylomicrons, very-low-density lipoproteins, low-density lipoproteins, high-density lipoproteins 

chylomicrons are made in

enterocytes

very-low-density lipoproteins (VLDL) have

high lipid content

low-density lipoproteins (LDL) are the

main cholesterol transport and HIGH LIPID CONTENT

high-density lipoproteins (HDL) have

low lipid content; absorbs cholesterol and carries it back to the liver (at the liver cholesterol can be flushed from the body)

the four classes of lipoproteins are all 

made in the liver 

intact TAGs cannot enter (be taken up by) tissues because they must have

lipolysis (lipid hydrolysis)

lipolysis (lipid hydrolysis) is the cleaving of

fatty acids from the glycerol backbones, achieved by lipoprotein lipase

lipoprotien lipase is found on 

capillary walls, particularly in tissues that are largely responsible for lipid synthesis (adipose tissue and mammary gland) and is stimulated by insulin

insulin also stimulates glucose uptake by tissues and stimulates 

lipoprotein lipase and uptake of TAGs by tissues 

lipogenesis is when 

simple non-lipid nutrients are converted to long-chain fatty acids and stored as triglycerides (happens a lot in adipose tissue) 

carbon sources for fatty acid synthesis will vary based on diet and mode of digestion and 

monogastrics utilize glucose as a major source, ruminants use acetate as a major source 

glycerol is needed for the backbone of TAGs

in all species - derived from glucose, FAs are esterfied to glycerol to make triglycerides

fatty acids are produced from

acetyl CoA - reguardless of the carbon source.

fatty acid synthesis occurs in the cytosol

FAs are built 2 carbons at a time, this continues until ~16 C long (palimtate) or 18 C long (stearic acid) 

lipid anabolism is the increasing rate of FA synthesis and increases

energy provided by diet (excess fat, glucose, aa), glycogen stores are full

decreasing rate of FA synthesis means they are

deficient in energy (fat, glucose, aa) and lipid catabolism will increase

De novo synthesis is the synthesis from non-fatty acid precursors and is the process by which 

cells make complex compounds like FA 

carbohydrate precursors (glucose, lactate, and pyruvate), amino acid precursors (alanine, BCAAs), and short-chain organic acids (acetate and propionate) are all parts of

De novo synthesis

lipogenesis is fatty acid or triacylglycerol synthesis from

preformed fatty acids (from diet or de novo FA synthesis), requires sourceof carbon for glycerol backbone 

tissue sites of de novo fatty acid biosynthesis are

liver and adipose tissue

some fatty acids can be synthesized in other tissues like

brain and lung

in the liver for de novo fatty acid biosynthesis, lipids must

be transported from the liver to the adipose tissue to increase fat mass (this happens in birds, fish, humans, and rodents)

adipose tissue is the site of de novo fatty acid biosynthesis in

all livestock species and young rodents

substrates for fatty acid biosynthesis

glucose, acetate, lactate, propionate

fatty acid biosynthesis requires

a source of carbon (usually 2-carbon precursors) and reducing equivalents (i.e. NADPH)

all species can utilize glucose to some extent as a substrate for fatty acid biosynthesis - in nonruminants 

glucose also is essential for lipogenesis from acetate (to provide G3P and NADPH via the pentose cycle) 

all species can utilize glucose to some extent as a substrate for fatty acid biosynthesis - in ruminants 

glucose is incorporated into fatty acids at about 1/10th the rate seen for acetate or lactate

all species can use this very effectively as a substrate

lactate

this substrate for fatty acid is only important in ruminants

propionate

acetate can be utilized to some extent as a substrate for fatty acid biosynthesis in all species - in nonruminants, 

if incubateed in the presence of glucose, acetate is incorportated into fatty acids at high rates. virtually no fatty acid synthesis occurs from acetate in the absence of glucose

acetate can be utilized to some extent as a substrate for fatty acid biosynthesis in all species - in ruminants

they have evolved to effectively utilize it

acetate, lactate, and glucose in combination as substrates for fatty acid biosynthesis

acetate inhibits lipogenesis from lactate and glucose, acetate provides >80% carbons to lipogenesis, lactate 10-20% and glucose <5%

most of the carbon from glucose enters fatty acid synthesis via 

glycolysis and the production of pyruvate

pyruvate enters the mitochondria and is converted to both OAA and AcCoA, which form citrate, the citrate exits the 

mitochondira and is hydrolyzed by ATP-cirtate lyase

the AcCoA is utilized for fatty acid synthesis and then the OAA is reduced to malate, when then is oxidatively decaboxylated (by NADPmalate dehydrogenase) back to 

pyruvate. This cycle can produce about ½ the NADPH required for fatty acid biosynthesis from glucose 

acetate is converted to AcCoA in the

cytoplasm

lactate follows the same pathway as

glucose; enters the pathway at pyruvate

propionate enters the fatty acid biosynthetic pathway after 

conversion to succinyl-CoA, fatty acid synthesis that incorporates propionate produces odd-chained fatty acids. 

storing excess nutrients or energy as fat can be advantageous because 

high energy density and low water content 

major sites of fatty acid synthesis are 

liver, adipose tissue, and mammary gland. 

animals can NOT synthesize all fatty acids

such as C18:2 and C18:3 and cats cannnot synthesize arachidonic acid (C20:4) 

start with acetyl-CoA formation from:

glucose, specific amino acids, and degraded lipids

fatty acid chains are formed when

2 carbon units are added - starting from carboxyl end to methyl end; ester bonds formed; up to 16 carbon FA can be formed; NADPH is required as an “energy source” for FA formation 

FA synthesis in ruminants is relatively similar to that of monogastrics except:

sources of carbon for acetly CoA: acetate, lactate, beta-hydoxy butyrate, dietary fatty acids

ruminants are unable

to convert glucose to fatty acids

lipolysis (breakdown of lipids) can create energy when the animal is in an

energy deficit - not getting enough feed, has increased energy demand 

catabolism of TAGs occurs in all tissues that have fat storage particularly important for adipose tissue, NEFAs are taken up by

tissues and oxidized

4 major steps in lipid catabolism

lipolysis of adipose tissue TAGs, glycerol enters glycolytic pathway, transport of NEFA to other tissues in blood, fatty acid uptake and oxidation by these tissues 

lipolysis =

lipid hydrolysis, breaking off fatty acids from glycerol (key enzyme: hormone sensitive lipase)

glycerol enters glycolitic pathway causing

glycolysis to produce energy and gluconeogenesis to produce glucose

NEFA=

product of lipolysis, pacted with albumin (a protein) 

fatty acid uptake and oxidation by these tissues leads to

beta oxidation (use the fatty acid for energy)

step 1 of lipid catabolism: lipolysis:

stimulated by an energy deficit and/or stress; stimulated by: cortisol, epinephrine, growth hormone

step 2 of lipid catabolism: glycerol enters a glycolytic pathway

primary glycolysis → energy, gluconeogenesis is also an option (get glucose as a product)

step 3 lipid catabolism: transport of NEFA to other tissues in the blood:

NEFAs are hydrophobic and attach to albumin (hydrophilic) when in the plasma; plasma NEFA concentration is related to fatty acid release (inc NEFA concentration = inc lipolysis = animal is in energy deficit)

step 4 lipid catabolism: fatty acid uptake and oxidation

complete oxidation of NEFA → CO2 and H2O which occurs in the mitochondria in two steps 

two steps that occur in mitochondria during fatty acid uptake and oxidation

FA is cleaved off in 2 carbon units to acetyl-CoA (=beta oxidation), acetyl-CoA is oxidized to CO2, H2O, ATP, and heat via Krebs cycle and respiratory transport chain (=oxidative phosphorylation)

total ATP produced (from beta-oxidation and the acetyl-CoA that enters the Krebs cycle) depends on the chain length of the fatty acid (NEFA) for 

palmitate (16 C), total ATP yield = 126 ATP, remember glucose = 32 ATP; therefore 16 C fat = ~4 times more ATP than glucose 

leptin is a protien hormone produced by

adipocytes (white adipose (fat) tissue)

more fat → more leptin produced brain senses “enough energy stored” →

eat less and burn more

the hypothalamus regulates

eating behavior (appetite), increase energy expenditure, negative-feedback mechanism.