Lecture 7.4 Lipid Metabolism

Lipid Metabolism
Instructor Muhammad Hassan
PART-IV
DIABETIC KETOACIDOSIS
• Presence of ketone bodies in the urine is known as ketouria often seen in diabetes
mellitus and starvation.
• In an insulin dependent diabetic patient, who failed to take insulin ,or in suffering in
illnesses or subjected to stress, blood glucose may rise markedly
• Though blood glucose level is high but body cannot utilize this glucose owing to the
absence of insulin.
• In response to this non-utilization of glucose, blood glucagon level rises.
• Elevated levels of glucagon cause adipose tissues to release increased amounts of
fatty acids, which are converted to ketone bodies by the liver
• Elevation in the concentration of ketone bodies in the blood results in acidosis.
Acidosis in diabetes it is called diabetic ketoacidosis
• Excretion of glucose and ketone bodies in the urine result in dehydration. Extremely
high level cause Ketoacidosis, if not treats ,may rapidly lead to coma and death
Biosynthesis of Fatty Acids: Lipogenesis
Lipogenesis vs. Fatty Acid Degradation

Lipogenesis Degradation of a fatty acids
Takes place in cell cytosol Takes place in mitochondrial
matrix
A multi-enzyme complex Enzymes are not complexed
called fatty acid synthase and the steps are
catalyzes reactions independent
Intermediates bonded to The carrier for fatty acid
acyl carrier protein (ACP) spiral is CoA
Depends upon reducing Dependent upon oxidizing
agent NADPH agents FAD and NAD+
Cholesterol Synthesis
• Synthesis of cholesterol, a C27 molecule, occur in liver and requires at least

15 acetyl CoAs and involves at least 27 separate enzymatic steps
• Once cholesterol has been formed, biosynthetic pathways are available to
convert it to each of the five major classes of steroid hormones.
• 7-Dehydration cholesterol, under the skin ,is converted to vitamin D3 by the
action of ultraviolet rays (sunlight)
• In the synthesis of bile salts also used as precursor of steroid hormones e.g.
sex hormones (testosterone, estrogen and progesterone), mineralocorticoids
and glucocorticoids.
Cholesterol Synthesis Location

• Cholesterol is synthesized in the cytoplasm
• It is synthesized from the cytosolic acetyl COA
Reaction of cholesterol synthesis
• NADPH2 and 3ATPs are used
• The Cholesterol synthesis is an endergonic process (utilizes ATPs)
• hydrolysis of high thioster bond of acetyl-CoA and the phosphate bond of ATP
drives the process toward the direction of cholesterol synthesis
Regulation of cholesterol synthesis
• HMG CoA Reduction is the rate limiting enzymes in cholesterol synthesis and is
subjected to different kinds of metabolic controls
Hormonal control
• Glucagon favors formation of the inactive (phosphorylated) form of HMG C0A
molecules resulting in decrease in the rate of cholestrol synthesis
• Insulin favors the formation of active (un -phosphorylated) form of HMG CoA
reduce resulting in increase in the rate of cholesterol synthesis
Cholesterol Synthesis
Clinical Notes Cholesterol
HYPERLIPIDMIAS
• These are group of disorders characterized by abnormally elevated levels of
any or all lipids and or lipoprotein in the blood
• It results from over production of lipoproteins or defects in various stages of
their degradation
FAMILIAL HYPERCHOLESTROLEMIA
• It is genetic disorder characterized by high cholesterol levels especially very
high levels of LDL in the blood and early cardiovascular diseases
• The defects is in the cellular receptors for LDL
• Hence LDL cannot be taken up normally by cells and degraded by lysomal
enzymes
• The resultant increases in the blood LDL is associated with xanthomas (lipid
deposits under the skin)and coronary artery diseases
Clinical Notes Cholesterol
ATHEROSCLEROSIS
• It is the formation and deformation of lipids-rich plaques in the intimae of
arteries
• It begins as fatty streaks containing foam cells ,which initially are
macrophages filled with lipids, particularly cholesterol esters
• This plaque then becomes fibrous and may occlude an artery and
cause a myocardial infarct or a cerebral infarct.
• The plaque formation is usually associated with abnormalities in plasma
lipoprotein metabolism
• In contrast to other lipoprotein, HDL has a cardio protective effects
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Lecture 7.4 Lipid Metabolism

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Lipid Metabolism

Instructor Muhammad Hassan

Lipogenesis vs. Fatty Acid Degradation

• Synthesis of cholesterol, a C27 molecule, occur in liver and requires at least

Cholesterol Synthesis Location

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