Fat and Steroid Metabolism in the Body

What are mono-, di-, and triacylglycerols?

monoacylglycerol: glycerol + 1 fatty acid

diaacylglycerol: glycerol + 2 fatty acids

triacylglycerol: glycerol + 3 fatty acids

For mono-, di-, and triacylglycerols, which are the storage form of fats?

Triacylglycerols are the primary storage form of fats in adipose tissue.

When would you see monoacylglycerols and diacylglycerols?

MAGs and DAGs are usually intermediates during triglyceride breakdown (lipolysis) or synthesis rather than long-term storage

What type of cell is an apidocyte?

A specialized fat-storage cell that stores triglycerides in large lipid droplets and releases fatty acids when the body needs energy

How do we get the fats we need?

Diet

Stored triglycerides in adipocytes

Conversion of carbohydrates into fats

Autophagy (recycling cellular components)

How much stored energy exists in the body? In what forms?

Blood glucose: ~170 kJ

Liver glycogen: ~8000 kJ

Muscle glycogen: ~100,000 kJ

Fat (triglycerides): ~400,000 kJ

Which bio molecule is the last resort to be broken down for energy?

Proteins are the last resort because they are essential for the structure and function of cells, muscles, enzymes, and many other tissues.

Why do fats provide more energy than carbohydrates?

Fatty acids contain many carbon atoms that can be oxidized

They are highly reduced, producing more ATP during oxidation

They are stored without water (anhydrous), making energy storage much more efficient

Why don’t we use fats as our primary source of energy if they provide more energy than carbohydrates?

Although fats contain more energy, they take longer to mobilize and transport.

They must be transported into mitochondria before oxidation

Cannot provide energy as rapidly as glucose

Why is there fat stored around our muscles?

They serve as local energy reserve. When energy is needed, the triglycerides are broken down into free fatty acids.

What becomes of the fat stored around our muscles?

The triglycerides are broken down into free fatty acids, which are taken up by muscle cells and oxidized to produce ATP

What signals an adipocyte to mobilize fats?

The hormones glucagon and epinephrine (adrenaline)

How do hormones signal an adipocyte to mobilize fats?

• hormones glucagon and epinephrine activate adenylyl cyclase

• cAMP increases

• cAMP activates PKA

• PKA phosphorylates hormone-sensitive lipase and peri lipids, allowing triglyceride breakdown

Which lipases are involved in the break triglyceride breakdown?

ATGL (Adipose Triglyceride Lipase)

HSL (hormone-sensitive lipase)

MGL (monoacylglycerol lipase)

What happens to the free fatty acids once liberated?

1. They leave adipocyte

2. They bind to serum albumin in bloodstream

3. They travel to tissues (e.g. muscle, heart, kidney)

4. They enter cells through fatty acids transporters

5. They are activated to fatty acyl-CoA and transported into mitochondria for beta-oxidation, producing acetyl-CoA for the citric acid cycle

What happens to the glycerol? What is it used for, and in what organ?

The glycerol travels to the liver where it is used for gluconeogenesis to help maintain blood glucose levels

What is a fatty acyl-CoA? How is it different from a fatty acid?

A fatty caul-CoA is a fatty acid that has been activated by attaching CoA

Fatty acids: free molecule

Fatty acyl-CoA: activated form that can undergo transport into mitochondria and beta-oxidation

How is the coenzyme A put onto the fatty acid?

The fatty acid is activated by an enzyme (acyl-CoA synthetase), which uses ATp to attach CoA, forming fatty acyl-CoA

Why is it necessary to put CoA onto the fatty acid

Only the activated form can be transported into mitochondria and metabolized by beta-oxidation

How does a fatty acyl-CoA get front he cytoskeleton to the mitochondrial matrix?

1. CPT-1 transfers the acyl group to carnitine on the outer mitochondrial membrane

2. The acyl-carnitine complex is transported across the inner mitochondrial membrane

3. CPT-II transfers the acyl group back to CoA inside the mitochondrial matrix

4. The fatty acyl-CoA is then ready for beta-oxidation

What is the structure of the steroid nucleus?

Consists of four fused carbon rings

What bio molecules use the steroid nucleus structure as part of their structure?

• Cholesterol

• Steroid hormones

• Vitamin D

• Bile acids/salts

Where in an animal would we find cholesterol

Cholesterol is found primarily in the plasma membrane (cell membrane) of animal cells, where it regulates membrane rigidity and fluidity

How does cholesterol influence membrane fluidity?

It buffers membrane fluidity by fitting between phospholipid tails.

What hormones are made from cholesterol?

It is the precursor for steroid hormones, including cortisol, aldosterone, testosterone, estrogen, progesterone

What vitamins are made from cholesterol?

vitamin D and A

Why are they called “fat-soluble” vitamins

Because they dissolve in fats rather than water and require dietary fats and bile salts for efficient absorption in the small intestine

What are bile salts

Cholesterol-derived molecules that emulsify dietary fats

This allows digestive enzymes to break them down and make fat absorption possible

What happens to the fats we eat

1. Bile salts emulsify dietary fats

2. Intestinal lipases digest triglycerides

3. Fatty acids are absorbed into intestinal cells

4. They are reassembled into triglycerides

5. Triglycerides are packaged into chylomicrons

6. Chylomicrons enter the lymph, then the bloodstream

7. Lipoprotein lipase releases fatty acids for tissues

8. Chylomicrons remnants are taken to the liver

What is the purpose of a chylomicrons

Transports dietary triglycerides and cholesterol from intestine to body tissues

What are the components of a chylomicrons?

• Triglycerides

• Cholesterol

• Phospholipids

• ApoB48

Where do chylomicrons go?

1. Formed in intestinal enterocytes

2. Travel through lymph

3. Enter bloodstream

4. Deliver triglycerides to tissues

5. Chylomicrons remnants are taken to the liver

What are the other lipoprotein particles?

VLDL

IDL

LDL

HDL

Which lipoprotein particle is the most dense?

HDL because it contains the highest proportion of protein relative to lipid

What is the role of apolipoprotein B48?

Found on chylomicrons, helps particles bind to cells

What is the role of ApoB100

Found on VLDL, IDL, and LDL

Mediates binding of these particles to cells, including LDL receptor recognition

What is the job of apolipoprotein CII (ApoCII)

ApoCIII activates LPL, allowing triglycerides in circulating lipoproteins to be hydrolyzed into free fatty acids for uptake by tissues

What is the pathway of the lipoproteins that carry cholesterol and fats away from the liver?

1. liver secretes VLDL

2. VLDL loses triglycerides through LPL

3. VLDL becomes IDL

4. IDL loses additional triglycerides and ApoCII/ApoE

5. IDL becomes LDL, which is rich in cholesterol

6. LDL delivers cholesterol to tissue or returns to the liver

When do the names of the lipoproteins change? What do they need to lose or gain

• as lipoproteins lose triglycerides and exchange apolipoprotein

VLDL → IDL: after losing triglycerides

IDL → LDL: after losing more triglycerides plus ApoCII and ApoE

Why is only LDL endocytosed?

LDL contains ApoB100, which is recognized by LDL receptors on cells

What happens after LDL is endocytosed?

Cells internalize LDL through receptor-mediated endocytosis, allowing cholesterol to be released and used for

membrane synthesis, steroid hormone production

What becomes of excess LDL particles that are not taken up by cells?

LDL particles that are not taken up by cells are returned to the liver or scavenged by macrophages

What are foam cells and why are they detrimental?

They are macrophages that have engulfed excessive amounts of LDL cholesterol

They accumulate in artery walls and contribute to atherosclerotic plaque formation.

This narrows arteries and increases the risk for CVD

Where does HDL originate from?

liver

What apolipoprotein does HDL contain/give up

Contains ApoCII and APoE, which it donates to VLDL and later retrieves from IDl as lipoproteins mature

What does HDL do that is so beneficial?

Performs reverse cholesterol transport. Picks up excess cholesterol from tissues, carries it back to the liver for recycling or excretion

Where does HDL go when it is done with its job

After collecting excess cholesterol, HDL returns to the liver, where the cholesterol can be reused or converted into bile acids/salts for elimination.

Can you read a lipid panel?

High LDL = increased CVD risk

High triglycerides = increased CVD risk

High HDL = lower CVD risks