1. Lipid Metabolism Part 1 Dr. Basima S.Ahmed Jaff Assist.Proffsor
PhD. Clinical Biochemistry

4. 1-Pancreatic secretion enzymes degrade dietary lipids in the small intestine is hormonally controlled .
2-Cells in the mucosa of lower duodenum and jejunum produce peptide hormone, cholecystokinin (CCK), in response to the presence of lipids and partially digested proteins entering these regions of the upper small intestine. CCK acts on the gallbladder (causing it to contract and Release bile. decreases gastric
Motility.
3- secretin, in response to the low pH of the chyme entering the intestine. the pancreas andthe liver to release a solution rich in bicarbonate .

7. Lipid malabsorption
Lipid malabsorption, caused by disturbances in lipid digestion and/or absorption disturbances can result from several conditions, including Cystic Fibrosis (causing poor digestion)

10. TG Biosynthesis

12. FATTY ACID OXIDATION
Sources of fatty acids
(a) Dietary sourcesFatty acids formed from the digestion of dietary lipids are carried to liver. From the liver, they are transported to cell in bound form with albumin.
(b) Endogenous sources As mentioned above, free fatty acids formed from body TG are used for energy production. Though the plasma free fatty acid level is lower than blood glucose level they are rapidly utilized by peripheral tissues. The plasma free fatty acid (FFA) has life of 3-4 minutes.
SiteFatty acid oxidation occurs in the mitochondria of all types of cells like liver, heart, adipose tissue, kidney, lung, skeletal muscle and some extent in brain.

14. 1. Oxidation by FAD
2. Hydration
3. Oxidation by NAD
4-cleavage

16. Regulation of β-oxidation
• Rate limiting step in the β-oxidation
formation of acyl-carnitine which is catalyzed by carnitine-acyl transferase-I (CAT-I). CAT-I is anallosteric enzyme. Malonyl-CoAis an inhibitor of
CAT-I.
– In well-fed state due to increased level of insulin,concentration of malonyl-CoA increases which inhibits CAT-I and leads to decrease in fatty acidoxidation.
– In starvation, due to increased level of glucagon concentration of malonyl-CoA decreases and
stimulates the fatty-acid oxidation

17. β-oxidation of a Fatty Acid with an Odd Number of Carbon Atoms;
final β-oxidation cycle, of odd carbon fatty acids a
3 carbon fragment propionyl CoA is formed
rather than 2 carbon fragment acetyl-CoA.
• Propionyl-CoA is converted to succinyl-CoA a constituent of citric acid cycle.
• Propionyl-CoA is carboxylated at the expense of an ATP to yield the D-methylmalonyl-CoA; catalyzed by propionyl-CoA carboxylase, a biotin enzyme.

19. Pathway of cholesterol biosynthesis

21. THANKS/Dr.Basema

22. Dr .Basima S. Ahmed Jaff PhD.Clinical Biochemistry
Lipid metabolism part2
Dr .Basima S. Ahmed Jaff
PhD.Clinical Biochemistry

23. Lipoprotein metabolism
Chylomicrone.
VLDL, LDL
HDL

27. 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.

28. 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

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

31. 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?

32. 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?

33. 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

34. 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.

35. 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.

37. 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.

38. 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.

42. PHOSPHOLIPIDS

45. Thank you
DR.Basema