LIPID METABOLISM

Types of Dietary Lipids and their

digestion
1. Triacylglycerols (Mainly)
2. Phospholipids
3. Cholesterol
4. Fat soluble vitamins (A, D, E& K)

• In the mouth: lingual lipase is not significant as food passes rapidly to the stomach
• In the stomach: gastric lipase acts shortly as it is destroyed by the high acidity (it acts only in infants
due to low acidity)
• In the intestine: pancreatic lipase is the main enzyme responsible for digestion of TAG, it converts
most of TAG into MAG (monoacyl glycerol) and free fatty acids
Fate of Absorbed Lipids

1) Fatty acid Oxidation for energy production

2) Gluconeogenesis (conversion to glucose): by conversion of glycerol to glucose
3) Synthesis of biologically active compounds; example: steroids
4) Formation of tissue fat: which enters in the structure of cells.
5) Storage: through lipogenesis.
6) Secretion: by lactating mammary gland in milk and by sebaceous gland in sebum.
Lipolysis

■ It is the break down of TAG of adipose tissues into glycerol and fatty acids.
■ This occurs by specific enzyme termed hormone sensitive lipase (HSL).

Regulation of lipolysis:
 Inhibited by: insulin hormone, i.e. after carbohydrate feeding.
 Stimulated by: anti-insulin hormones, i.e. fasting, starvation, low carbohydrate diet
or stress
Lipogenesis

■ It is synthesis of TAG by esterification of fatty acids with glycerol.

■ The active form of glycerol is glycerol-3-phosphate, while the active form of fatty
acids is acyl-CoA.
■ Glycerol-3-phosphate comes from DHAP which is an intermediate of glycolysis
B-Oxidation of Fatty Acids

■ It is the pathway by which activated fatty acids (acyl-CoA) are converted to Acetyl Co-
A which then enters Kreb's cycle to produce ATF.
■ Site: occurs in the mitochondria of many cells except RBCs and Brain.
■ Function: It is the main source of energy during fasting and starvation.
■ Energy production: 106 ATP are produced from oxidation of one Fatty acid molecule
Energy production OF PALMITIC ACID

7 FADH2 +7 NADH+ 8 active acetate

■ 7 FADH2 (7x1.5 10.5 ATP) +
■ 7 NADH (7x2.5- 17.5 ATP) +
■ 8 active acetate = TCA= (8x10= 80 ATP) = 108ATP
■ - 2 ATP used for FA activation = 106 ATP
Metabolism of Ketone Bodies
■ Ketone bodies are:
1- Acetoacetate
2-β -hydroxy butyrate
3-Acetone (volatile)
■ They are all formed from condensation of two molecules of Acetyl Co-A
■ During high rates of Fatty acids oxidation in Liver = large amounts of Acetyl Co-A are
produced above the capacity of kreb's cycle
■ Acetyl Co-A is redirected to synthesize ketone bodies in Liver (Ketogenesis)
■ Then ketone bodies are transported from liver to other organs to be used for Oxidation and
energy production (Ketolysis)
Importance of ketone body formation

■ Ketone bodies are formed in the liver (ketogenesis)

■ Ketone bodies are oxidized by the extrahepatic tissues (Ketolysis) (e.g heart and
muscles) for production of energy during fasting, starvation and carbohydrate
deficiency .
■ Oxidation of ketone bodies is easier than oxidation of fatty acids.
■ The brain can accommodate for oxidation of ketone bodies within 5-6 days of
starvation, but never can oxidize fatty acids which cannot cross the blood brain
barrier
Complications of Ketone bodies:

■ Increased blood level of ketone bodies leads to acidosis a as they are relatively
strong acids, If acidosis is not controlled, it may lead to academia, coma and death.
Management:

■ 1. IV Glucose if low carbohydrate diet or starvation

■ 2. IV Glucose and insulin if the cause is diabetes
■ 3. Bicarbonate to correct acidosis
■ 4. K+ to correct electrolyte loss, and fluids to correct dehydration
Cholesterol Metabolism

■ Site: All cells can synthesize their own cholesterol

■ Regulation:
1. It is stimulated by insulin and carbohydrate feeding. .
2. It is inhibited by fasting and anti-insulin hormones secretion
Cholesterol itself produces negative feed back inhibition on the enzyme.
Excretion and Functions

■ Excretion: By Synthesis of bile acids which is stimulated by thyroxine hormone.

■ Functions of cholesterol:
1. Important constituent of all cell membranes
2. Formation of plasma lipoproteins.
3. Synthesis of steroid hormones
4. Synthesis of vitamin D
5. Synthesis of bile acids and salts (excretory form of Cholesterol).
Cholesterol Levels and Complications
■ The total plasma cholesterol level is 120-200 mg/dl.
■ Hypocholesterolemia: Decreased plasma level of cholesterol below 120 mg/dl
1. Diet low in carbohydrate, cholesterol or saturated fatty acids.
2. Liver diseases.
3. Hyperthyroidism
■ Hypercholesterolemia: Increased plasma level of cholesterol above 240 mg/dl .
1. Diet rich in carbohydrates, saturated fatty acids and cholesterol.
2. Diabetes mellitus.
3. Hypothyroidism. .
4. Coffee drinking and cigarette smoking.
■ Hypercholesterolemia will lead to atherosclerosis and coronary heart diseases
Diabetes Mellitus (DM)
■ It is a metabolic disease characterized by disturbance in carbohydrates, lipid and
protein metabolism.
■ It is due to decrease insulin/anti-insulin ratio.
■ Symptoms include polyuria, polydipsia, polyphagia, delayed healing of wounds and
weight loss.
■ Metabolic changes in DM: All the metabolic changes are due to change in
insulin/anti-insulin ratio, which produces changes reversal to insulin action
Changes in carbohydrate metabolism:
1) - Decrease glucose uptake, glucose oxidation and glycogenesis.
2) - Increase glycogenolysis and gluconeogenesis.
3) This leads to hyperglycemia- glucosuria (when blood glucose exceeds renal threshold
of glucose which is 180 mg/dl) → polyuria → loss of electrolytes dehydration →
polydepsia (feeling of thirst).
Changes in lipid metabolism:
1. Decrease lipogenesis and increase lipolysis acids → excessive release of fatty
→ This leads to weight loss.
2. Ketogenesis → ketosis and may be coma
Changes in protein metabolism:
- Decrease protein synthesis and increase protein catabolism.
- Leading to increased sensitivity to infection & delayed healing of wounds.