Week 5: Lipid Metabolism

Lipids: long chains of carbons varying in length and level of saturation

• Categorised based on the number of carbons and types of bonding

• Cholesterol is important as it stabilizes the membrane, it is important for bile acid, and vitamin D synthesis

• Lipids cannot be carried in the blood as it is mostly water

—> lipids cannot be carried in the blood since it is mostly water

Types of lipids:

simple lipids: groups of lipids composed of fatty acids, glycerols and alcohols

• fats, oils and waxes

complex lipids: groups of lipids that contain other groups apart from fatty acids and glycerols

• phospholipids, lipoproteins, lipopolysaccharides

Lipoproteins: packaged fat and cholesterol

• lipid core and a surface coat, phospholipids are surrounding it

• apoproteins which surround it determine their function

4 main lipoproteins: lowest protein to highest protein (highest lipid to lowest lipid)

1. chylomicron = 90% TAG, 10% Cholesterol Esters

2. VLDV (very low density lipoprotein) = TAG and cholesterol esters

3. LDL = cholesterol esters

4. HDL = cholesterol esters

Chylomicrons = important for dietary TAG

• ingested in the small intestine

Chylomicrons in the blood:

1. chylomicrons doc onto LPL

2. LPL breaks bonds that join fatty acids and glycerol

3. chylomicron remnants are taken through the blood into the liver

Basically:

• chylomicrons from the gut goes through extrahepatic tissue first

• TAG is sucked out leaving the chylomicron remnant

• this is taken to the liver, cholesterol is recycled and can be used in in many ways

Chylomicron remnant in the liver —> cholesterol is removed

• Cholesterol is important for bile, bile goes into the small intestine and helps to breakdwon fats, some bile is reabsorbed

• Cholesterol is also carried in the LDL, LDL takes cholesterol from the liver to extrahepatic tissue (other tissue)

Steps:

• liver released VLDL

• muscles take TAG and use it through beta oxidation to break it down for energy

• adipose tissue will also breakdown tag to release fatty acids to go to the muscles and liver

• the glycerol will go back to the liver and is then converted into glucose through gluconeogenesis.

regulating fatty acid utilisation:

• lipolysis of triacylglycerol results in free fatty acids

• fatty acids undergo reesterification to repackage into TAG or they can be sent from adipose tissue where they are needed for energy

• transport acyl-CoA into the mitochondria

• availability of FAD and NAD for beta oxidation

hormone sensitive lipase

= lipase = enzyme that hydrolyses TAG = FA and glycerol

• pacnratic lipase (digestive enzyme)

• lipoprotein lipase (adipose epithelial cell)

HSL activated by protein kinase

phosphorylated when active

HSL inactive form by phosphatase

REGULATING HSL:

Process of lipolysis and re-esterification:

when lipids are broken down in adipose tissue, they either release fatty acids and glycerol or will be repackaged. when needing to leave the cell, fatty acids will be encouraged to go out and be used for energy instead of being repackaged

Transportation of fatty acids across a membrane: fatty acid translocase

During exercise: interstitial fluid which is between the blood and the sarcoplasm of muscle recieves fatty acids through

1. albumin, VLDL, or chylomicrons take fatty acids

2. LPL which is on the endothelial cells of the capillary, transports FA down a concentration gradient into the sarcoplasm

3. mostly done by FAT CD36 (fatty acid translocase)

Storage in muscles:

• If we dont want to use fatty acid as energy, LPL will get active and take the fatty acids into the cell and we will store it in muscle

• fatty acids will get activated by acyl-CoA

• in a trained individual, lipid droplets are closer to the mitochondria as this is the site for beta oxidation which will need quick access to the lipid droplets

• after exercise, lipid droplets decrease in size by a half, intramuscular TAG can potentially increased in trained individuals.

Lipolysis of intramuscular triacylglycerol:

• Protein Kinase activates inactive HSL

  • stimulated by the release of calcium ions, adrenaline and AMP

• Protein Kinase phosphorylates HSL and makes it active

SUMMARY: nothing is rate limiting

1. fatty acids leave adipose tissue down a concentration gradient

2. fatty acids bind to albumin (a protein) in the blood

3. fatty acids are removed from the blood and enter the cell through a concentration gradient

Carnitine shuttle:

Once fatty acids are in the cell, they must be transported into the mitochondria for beta oxidation to give Acetyl CoA

• mitochondria has 2 membranes

  • outer membrane = permeable to lipids

  • inner membrane = impermeable to lipids

• CPT1 sits on the outer membrane and attaches to the acyl, removing the CoA and replacing it with carnitine

• CACT helps the carnitine acyl into the mitochondria

  • Acyl carnitine needs to be removed and replaced with the CoA

• CPT2 removers the carnitine and reattaches the CoA

Basically:

CPT1: takes off the CoA

CAPT: moves acyl carnitine across the impermeable membrane

CAPT2: removes the carnitine and replaces it with CoA

• Acetyl CoA now enters the TCA cycle, producing NADH and FADH2 to give us ATP

B-oxidation; B-HAD is a rate limiting enzyme

• beta oxidation repeats itself until there are not carbons left to be converted into Acetyl CoA

When comparing energy from fat oxidation is 39.4, grams oxidised per min is more but there is less energy in each gram compared to CHO which burned 15.6 grams.

Fatty acid increase drives fatty acid oxidation increase

• more fatty acids in the blood = more fatty acid oxidation, increases muscle glycolysis = increase of fatty acids in the mitochondria

Cholesterol

Too much LDL can be dangerous as it can result in problems in blood vessels.

• LDL has a very long life, it sits in the body for 1.5 to 2 days

• because they are in the bloodstream for so long, they are subject to damage

Why is HDL seen as “good”?

• HDL is the best single lipid predictor of CVD as it is negatively related

Its life cyle is complex, when a cell has too much cholesterol, it will express SRB

• HDL attaches on to SRB to remove excess cholesterol and transport it to the liver

  • bile, steroid hormones, membrane stability and support

How can we change lifestyle to reduce cholesterol?

• a study showed that plant sterols cause less cholesterol to be less abosrbed

• aerobic training and resistance taining

• high fat diet- increase chylomicrons