1. Clinical significance of lipids
Following diseases are associated with abnormal chemistry or metabolism of lipids-
Obesity
Atherosclerosis
Diabetes Mellitus
Hyperlipoproteinemia
Fatty liver
Lipid storage diseases
Biochemistry for medics
6/29/2012

2. Essential fatty acids
Polyunsaturated fatty acids such as Linoleic and Linolenic acids are essential for normal life functions. They are therefore characterized as essential fatty acids.
Arachidonic acid is considered as semi essential fatty acid since it can be synthesized from Linoleic acid .
Essential polyunsaturated fatty acids can be classified as belonging to one of two "families", the omega-6 family or the omega-3 family.
Fatty acids belonging to these two families differ not only in their chemistry, but also in their natural occurrence and biological functions.
Biochemistry for medics
6/29/2012

3. Significance of essential fatty acids
Components of cell membranes, structural elements of gonads and mitochondrial membrane
Required for brain growth and development
Precursors of Eicosanoids
Play important role in vision
They have a cardio protective role- Lower serum cholesterol and increase HDL levels
Prevent fatty liver formation
Deficiencies of essential polyunsaturated fatty acids may cause a wide variety of symptoms, including retarded growth in children, reduced fertility and pathologic changes in the skin.
Biochemistry for medics
6/29/2012

4. Glycerol-Structure and significance
Also called ‘Glycerin’.
Trihydric alcohol as it contains three hydroxyl groups
Can be obtained from diet, from lipolysis of fats in adipose tissue and from glycolysis.
Can be utilized for the synthesis of triacylglycerols, phospholipids, glucose or can be oxidized to provide energy
Used as a solvent in the preparation of drugs and cosmetics
Nitroglycerine is used as a vasodilator
Biochemistry for medics
6/29/2012

5. Significance of Cholesterol
Cholesterol is widely distributed in all cells of the body but particularly in nervous tissue.
It is a major constituent of the plasma membrane and of plasma lipoproteins.
It is synthesized in many tissues from acetyl-CoA and is the precursor of all other steroids in the body, including corticosteroids, sex hormones, bile acids, and vitamin D.
Cholesterol is a major constituent of gallstones.
Its chief role in pathologic processes is as a factor in the genesis of atherosclerosis of vital arteries, causing cerebrovascular, coronary, and peripheral vascular disease.
Biochemistry for medics
6/29/2012

6. Normal serum level and Variations
Normal level of serum total cholesterol ranges between mg/dL
Physiological variations-
Low at the time of birth, increases with advancing age.
The level is increased during pregnancy
Pathological Variations-
a) Low cholesterol (Hypocholesterolemia)-
Thyrotoxicosis, anemia, hemolytic jaundice, wasting diseases and malabsorption syndrome.
Biochemistry for medics
6/29/2012

7. Pathological variations of serum Total Cholesterol (Contd.)
B) Hypercholesterolemia-
Nephrotic syndrome
Diabetes Mellitus
Obstructive Jaundice
Myxoedema
Xanthomatous biliary cirrhosis
Hypopituitarism
Familial Hypercholesterolemia
Idiopathic
Biochemistry for medics
6/29/2012

8. Other sterols of biological Importance
7- dehydrocholesterol- also called as Provitamin D3 (Precursor of vitamin D)
Ergo sterol-plant sterol (First isolated from Ergot- Fungus of Rye)
Stigmasterol and Sitosterol- Plant sterols
Coprosterol (Coprostanol)- Reduced products of cholesterol- found in feces
Other steroids- Bile acids, adrenocortical hormones, gonadal hormones, D vitamins and Cardiac glycosides.
Biochemistry for medics
6/29/2012

9. Properties of triglycerides
Colourless, odourless and tasteless
Insoluble in water
Specific gravity is less than 1.0, consequently all fats float in water
Oils are liquids at 200C, they contain higher proportion of Unsaturated fatty acids
Fats are solid at room temperature and contain saturated long chain fatty acids
Triglycerides are the storage form of energy in adipose tissue
Triglycerides in the body are hydrolyzed by Lipases
Biochemistry for medics
6/29/2012

10. Lipid storage diseases(Sphingolipidosis)
Enzyme deficiency
Nature of lipid accumulated
Clinical Symptoms
Tay Sach’s Disease
Hexosaminidase A
GM2 Ganglioside
Mental retardation, blindness, muscular weakness
Fabry's disease
α-Galactosidase
Globotriaosylceramide
Skin rash, kidney failure (full symptoms only in males; X-linked recessive).
Metachromatic leukodystrophy
Arylsulfatase A
Sulfogalactosylceramide
Mental retardation and Psychologic disturbances in adults; demyelination.
Biochemistry for medics
6/29/2012

11. Lipid storage diseases(Sphingolipidosis)- contd.
Enzyme deficiency
Nature of lipid accumulated
Clinical symptoms
Krabbe's disease
β-Galactosidase
Galactosylceramide
Mental retardation; myelin almost absent.
Gaucher's disease
β -Glycosidase
Glucosyl ceramide
Enlarged liver and spleen, erosion of long bones, mental retardation in infants.
Niemann-Pick disease
Sphingomyelinase
Sphigomyelin
Enlarged liver and spleen, mental retardation; fatal in early life.
Farber's disease
Ceramidase
Ceramide
Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life
Biochemistry for medics
6/29/2012

12. DISORDERS ASSOCIATED WITH IMPAIRED BETA OXIDATION
1. Deficiencies of carnitine or carnitine transferase or translocase
Symptoms include muscle cramps during exercise, severe weakness and death.
Muscle weakness related to importance of fatty acids as long term energy source
Hypoglycemia and hypo ketosis are common findings
Diet containing medium chain fatty acids is recommended since they do not require carnitine shuttle to enter mitochondria.
Biochemistry For Medics
9/18/2018

13. 2) Jamaican Sickness
Jamaican vomiting sickness is caused by eating the unripe fruit of akee tree, which contains the toxin hypoglycin, that inactivates medium and short-chain acyl-CoA dehydrogenases, inhibiting β oxidation and thereby causing hypoglycemia.
3) Dicarboxylic aciduria  is characterized by-
i) Excretion of C6–C10 -dicarboxylic acids and
ii) Nonketotic hypoglycemia which is caused by lack of mitochondrial medium chain acyl-CoA dehydrogenases.
Biochemistry For Medics
9/18/2018

14. 4) Acute fatty liver of pregnancy
Manifests in the second half of pregnancy, usually close to term, but may also develop in the postpartum period.
The patient developed symptoms of hepatic dysfunction at 36 weeks of gestation.
Short history of illness, hypoglycemia, liver failure, renal failure, and coagulopathy are observed.
Diagnosis is made based on an incidental finding of abnormal liver enzyme levels.
Affected patients may become jaundiced or develop  encephalopathy from liver failure, usually reflected by an elevated ammonia level.
Profound hypoglycemia is common.