1. Lipid metabolism part2
Dr .Basima S. Ahmed Jaff

2. Lipoprotein metabolism
Chylomicrone.
VLDL, LDL
HDL

6. Reverse Cholesterol Transport
• This is the process whereby excess cholesterol contained in extrahepatic tissue is taken to the liver, through HDL metabolic cycle for utilization or excretion through the bile. • The LCAT esterifies the cholesterol content of HDL
to prevent it from re-entering the cells. If the cholesterol is not esterified within the HDL particle, the free cholesterol can leave the particle by the same route that it entered. Thus esterification by LCAT serves to trap cholesterol within the lipoprotein, preventing it from deposition in the tissues.
Significance of reverse cholesterol transport
• By reverse cholesterol transport cellular and lipoprotein cholesterol is delivered back to the liver.
This is important because the steroid nucleus ofcholesterol cannot be degraded; and the liver is the only organ that can remove excess cholesterol by secreting it in the bile for excretion in the feces.
• Revese cholesterol transport prevents deposition of cholesterol in the tissues and is thought to be antiatherogenic. An elevated HDL cholesterol (good cholesterol) level decreases the risk of coronary heart disease.

7. Hypercholesterolemia
In a normal adult, the total plasma cholesterol ranges form 150–250 mg/100 ml.An ↑ in plasma cholesterol more than 250 mg/100 ml is known as hypercholesterolemia and is seen in the following conditions:
1-Diabetes mellitus: ↓ of insulin,↑ rate of lipolysis. ↑ rate of lipolysis results
in↑FFAin circulation which in↑ acetyl-CoA. Excess of acetyl-CoA are diverted for cholesterol biosynthesis
2. Hypothyroidism:This is due to ↓ in the HDLReceptors on hepatocyte in hypothyroidism and due to ↓ synthesis of 7-α-hydroxylase that requires for the conversion of cholesterol to bile acids. Thyroid hormone ↑ the synthesis of 7-α-hydroxylase.
3. Obstructive jaundice:Due to ↓ excretion of cholesterol through bile.
4. Familial hypercholesterolemia:It is a genetic disease caused by deficiency or malfunction of the LDL receptors. In the absence of these receptors, the liver cannot take LDL and there is no release of cholesterol of LDL into the liver. Therefore, they do not cause feedback inhibition of cholesterol synthesis and lead to ↑ cholesterol formation

9. Fatty liver may occur due to:
1. Overproduction of triacylglycerol in liver.
2. Impaired synthesis of VLDL.

10. Case History
A 60-year-old woman was referred to a hospital. She was noted to have hypertension. The plasma cholesterol level was 390 mg/dL. An angiogram of the right carotid artery demonstrated a narrowed lumen and the concentration of LDL was elevated.
Questions
a. What is your probable diagnosis?
b. What is the normal plasma cholesterol level?
c. By which enzyme is cholesterol biosynthesis regulated?
d. Which lipoprotein has protective effect against the disorder?

11. Case History
A 30-year-old woman was hospitalized, with an acute myocardial infarction. Her plasma cholesterol and LDL level were highly elevated. She was found to have familial hypercholesterolemia.
Questions
a. How are LDL formed?
b. What apoprotein does LDL contain?
c. What is the function of LDL?
d. Why LDL is called bad cholesterol?

12. Ketone Bodies - formed in the liver and oxidized in skeletal and heart muscle and the renal cortex. Brain adapts to use them under starvation conditions

13. Regulation of Ketogenesis
1. Factors regulating lipolysis:FFA the precursors of ketone bodies ↑ from lipolysis of TG in adipose tissue, also regulate ketogenesis. The hormone glucagon ↑lipolysis which in turn ↑ketogenesis, whereas insulin ↓ lipolysis and ketogenesis.
2. Factors regulating β-oxidation of fatty acids Carnitin acyl transferase I, regulates ketogenesis during starvation. and formation of ketone bodies.
3. Factors regulating oxidation of acetyl-CoA:In turn,
the acetyl-CoA, formed in β-oxidation in liver
mitochondria, has two possible fate these conditions, acetyl-CoA is diverted to the formation of acetoacetate.

14. moderately strong acids, ↑ levels of these
Ketoacidosis
• Since acetoacetate and β-hydroxybutyrate are
moderately strong acids, ↑ levels of these
ketone bodies ↓ the pH of the bood and cause
metabolic acidosis.The acidosis caused by over
production of ketone bodies is termed as ketoacidosis.

16. Disorders of Ketone Body Metabolism
Ketosis
• Normally the concentration of ketone bodies in blood is very low (less than 0.2 mmol/L) but in fasting and in diabetes mellitus it may reach extremely↑
• In addition to β-hydroxybutyrate and acetoacetate, the blood of diabetics also contains acetone. Acetone is very volatile and is present in the breath of diabetics, it gives sweet fruity odor. The overall condition (ketonemia and ketonuria) is called ketosis.

17. ALCOHOL METABOLISM
ethanol is a drug. It has high energy content, yielding about 7.1 kcal/g on oxidation. Liver is the major site of ethanol oxidation. At least 3 enzyme systems
1. Alcohol dehydrogenase (zinc dependent enzyme). principal pathway for ethanol oxidation. operational for acute intoxication when the blood alcohol concentration (1–5 mmol/L).
2. Microsomal ethanol oxidizing system (MEOS). MEOS appears to be a secondary enzyme system for ethanol clearance. In the chronic alcoholic, ↑ in MEOS activity
3. Catalase of peroxisomes. The role of catalase in biological oxidation of ethanol is controversial Only 2–10% of ethanol is excreted unoxidized in the urine and lungs.

21. PHOSPHOLIPIDS

24. Thank you
DR.Basema