NRSG 202 - Lipid Metabolism

Can lipids dissolve in blood? Why?

Blood is aqueous and lipids are hydrophobic, so they cannot dissolve in blood

What structure allows lipids to be transported in the blood?

Lipoproteins

Lipoproteins

lipid proteins that allow lipids to be transported in the blood

2 layers of lipoproteins

• Outer shell of protein: can interact with water

• Inner core of lipids

3 substances contained in the inner lipid core of lipoproteins

1. Phospholipids

2. Triglycerides

3. Cholesterol

4 classes of lipoproteins

1. Chylomicrons

2. VLDLs (very low-density lipoproteins)

3. LDL (low density lipoproteins)

4. HDLs (high density lipoproteins)

75% of the cholesterol in the blood comes from which lipoprotein?

LDLs

Chylomicrons

largest and lightest lipoproteins

Chylomicron function

transport dietary lipids to adipose tissue for storage

Makeup of chylomicrons

85% triglyceride, 7% phospholipids, 6-7% cholesterol, 1-2% protein

Transport of dietary fats mechanism

Dietary fats → small intestines → lacteals → lymph → venous blood → circulation

Apoproteins

proteins in a lipoprotein that function in lipid transport

2 apoproteins in chylomicrons

• ApoC2

• ApoE

ApoC2 function

activate endothelial lipoprotein lipase - removes fatty acids from the triglycerides to be stored in adipose tissue

ApoE function

binds to receptors on hepatocytes to be taken out of circulation

Where are VLDLs formed?

endogenous lipoproteins formed in the hepatocytes

VLDL makeup

50% triglyceride, 20% cholesterol, 20% phospholipids, 10% protein

VLDL function

Transport lipids make in the liver to adipose tissue for storage

Apoproteins in VLDL

ApoC2

ApoC2 function in VLDLs

removes fatty acids from the triglycerides to be stored in adipose tissue - VLDLs converted into LDLs in this process

How are LDLs made?

Derived from VLDLs

LDL makeup

50% cholesterol, 25% protein, 20% phospholipids, 5% triglyceride

LDL function

Delivers cholesterol to cells in order to repair membranes, synthesize steroid hormones, and make bile salts

Apoproteins in LDL

ApoB100

ApoB100 effect

binds to cell receptors and facilitates receptor-mediated endocytosis of cholesterol

Ecess LDL impact

formation of fatty plaques in arteries

Where is HDL made?

made by liver and small intestines

HDL makeup

40-45% protein, 30% phospholipid, 20% cholesterol, 5-10% triglycerides

HDL function

Remove excess cholesterol from body cells and transport to liver for elimination

Lipid profile test

Tests the ratios of the different types of cholesterol, returning the health risk for certain cardiovascular diseases

Total cholesterol expected value

< 200 mg/dL

LDL cholesterol expected value

< 130 mg/dL

HDL cholesterol expected value > 40 mg/dL

Triglycerides expected value

10-190 mg/dL

Risk ratio

Total cholesterol/HDL

Risk ratio ideal value

<= 4

What does a high risk ratio value indicate?

indicates that an individual is at a greater risk of developing coronary artery disease

3 potential fates of lipids

1. Oxidized into glycerol to make ATP

2. Stored for later in adipose tissue or liver

3. Used to synthesize other molecules

3 ways that lipids are used in the body

1. Phospholipids for cell membranes

2. Lipoproteins

3. Myelin sheath (nervous system)

Lipolysis

 beta-oxidation removes 2 carbons from fatty acid → acetyl-CoA

What enzyme mediates lipolysis?

Lipase

4 factors that trigger lipolysis

1. Epinephrine and norepinephrine (sympathetic)

2. Cortisol

3. Thyroid hormone (TH)

4. Insulin-like growth hormone

Factor that inhibits lipolysis

Insulin

Lippogenesis

making triglycerides by joining glycerol and fatty acids to make triglycerides (or from amino acids, glucose, etc.)

What needs to happen for lipogenesis to occur?

Abundant ATP and glucose

What triggers lipogenesis?

Result of an accumulation of acetyl-CoA and glyceraldehyde-3-phosphate (G3P)

Ketogenesis

creation of ketones derived from acetyl-CoA

3 ketone bodies

1. CoA

2. Beta-hydroxybutyric acid

3. Acetone

Ketone bodies function

Can be used to make ATP

Ketosis

buildup of ketone bodies that can lead to a buildup of acid and ketoacidosis

What condition is ketosis associated with and why?

diabetes: lack of insulin → excess beta-oxidation

Main sign of diabetic ketoacidosis

Fruity breath

Where does the digestion of lipids begin?

Duodenum

2 substances required for digestion of lipids

1. Pancreatic lipase

2. Bile salts

Can lipids be dissolved in the small intestines?

No, they are hydrophobic and the small intestines contain water

How are large fat globules broken down?

bile salts emulsifies the large lipids globules → small lipid globules

Function of emulsification

Increases surface area of the fat for digestion

How are small fat globules broken down?

Lipolysis through pancreatic lipase

What are small lipid globules broken down into?

1. Monoglycerides (fatty acid attached to glycerol)

2. Free fatty acids

2 types of free fatty acids

1. Short-chain fatty acids

2. Long-chain fatty acids

How are free fatty acids further processed for digestion?

Free fatty acids come together with bile salts and lecithin to form micelles that can be absorbe

Micelles

monoglycerides and long-chain fatty acids

How are micelles further processed for digestion?

Micelles are broken down in small intestines (villi) and made into chylomicrons

Process of lipid digestion and absorption as a chylomicron

Chylomirons travel into the lacteal of villus → thoracic duct → venous circulation

How do short-chain fatty acids enter the bloodstream?

Short-chain fatty acids can cross the cell via simple diffusion and do not need to be transported through micelles

Overall process of large lipid globule to lacteal

 large fat globule → emulsification (bile salts) → small fat globules → lipolysis (pancreatic lipase) → monoglycerides and free fatty acids → mixed with bile salts and lecithin → micelle  → absorption into the brush border → broken down and triglycerides are reassembled into chylomicron inside enterocyte → absorbed into lacteal