LIPIDS: CLASSIFICATION, PUFAS, LIPOPROTEINS, KETONE BODY SYNTHESIS & UTILIZATION

Lipids are essential biomolecules involved in various physiological processes, including energy storage, cell membrane structure and function, and signalling pathways. A good understanding of lipids is therefore important for understanding how the body functions at a molecular level.

Besides, Lipids are one of the most heavily tested topics in the NEET PG exam, and questions related to lipid metabolism and function carry significant weightage.

Read this blog further to get a quick overview of this high-yield biochemistry topic for NEET PG/NExT exam preparations. In this blog we’ll cover classification of lipids, PUFAs, lipoproteins, ketone body synthesis and ketone body utilization.

BASICS

Lipid: Any compound which is insoluble in water & soluble in non-polar organic solvent

• Made of fatty acid and alcohol joined by ester bond formed by removal of H₂O

CLASSIFICATION OF LIPIDS

Simple Lipids

• Base alcohol is glycerol

Phospholipid (PL)

Phospholipases: Enzymes which hydrolyse phospholipids at different places

Cardiolipin

• Complex phospholipid

• Phosphatidic acid = Glycerol + 2 FAs + P
• So, product of hydrolysis of cardiolipins = 3 glycerol + 4 FA + 2 P
• Can be antigenic due to its complex nature. 
• E.g. Anti-Phospholipid Syndrome
  • Occurs due to Anticardiolipin antibodies formed in body
  • C/f are thrombotic condition and disease females with history of recurrent abortions

Phospholipids Types

1. GlyceroPhospholipids Parent alcohol: Glycerol

2. SphingoPhospholipids Parent alcohol: Sphingosine  Sphingosine is an unsaturated amino alcohol

Glycolipids

• Made of Alcohol + FA + Carbohydrate
• Phosphate & base is never present
• Alcohol glycerol is never present
• Alcohol used is sphingosine (so, aka glycosphingolipids)

Types

1. Glucosylceramide / Glucocerebrosid
   • Sphingosine + FA + glucose
     • Sphingosine + FA = ceramide  
     • Ceramide + Glucose = Glucosylceramide or Glucocerebroside
   • Never found in CNS but always found in extra neural tissues
2. Galactosylceramide/Galactocerebroside
   • Sphingosine + FA + Galactose
   • Ceramide + Galactose = Galactosylceramide/ Galactocerebroside
   • Always found in CNS

PUFAs

Polyunsaturated Fatty Acids (PUFAs) means FAs having ≥ 2 double bonds

• aka Essential FAs (EFA) - they cannot be synthesized in our body and needs to be essentially taken in diet

Categories of PUFAs

Omega-3 category	Omega-6 category
Cervonic acid/DHA (DocosaHexaenoic Acid) 22 C (docosa) & 6 = (hexaenoic) Source: Fish oil α-Linolenic acid 18 C & 3 = Source: Flaxseed oil, Soybean oil) Timnodonic acid/EPA (EicosaPentaenoic Acid) 20 C (eicosa) & 5 = (pentaenoic) Source: Fish oil	γ–Linolenic acid 18 C & 3 = Source: oil of evening primrose Linoleic acid 18 C & 2 = Source: Safflower oil Arachidonic acid 20 C & 4 = Source: Animal Fats

• Any fatty acid starting from “L” have same number of carbons e.g. α-Linolenic acid, γ–Linolenic acid and Linoleic acid all have 18 carbons
• Smaller Name- Linoleic = 2 double bonds
• Bigger name - Linolenic = 3 double bonds

Important information

• DHA
  • is required for brain development of first 2-3 years of life so, Health drinks are fortified with DHA.
  • Breast milk always contains DHA.
• α–Linolenic acid is precursor of ω-3 category means if α–Linolenic acid is taken in diet, other two ω-3 FAs can be made form it in the body.
• Linoleic acid is precursor of ω-6 category and can be used to make other two ω-6 FAs in the body
• Most Essential FA is - Linoleic acid as it can make arachidonic acid which is required for PGs and Leukotrienes synthesis.
• PUFAs which are cardioprotective: ω-3 PUFAs

LIPID TRANSPORT

• Polar substance is soluble in polar medium and non-polar substance is soluble in non-polar medium 
• Transport medium in our body is blood and Blood is water based, hence it is polar
• So, carbohydrate & proteins which are polar can easily dissolve in blood and thus can be easily transported from one place of body to another 
• But dietary Lipids due to their non-polar nature cannot be dissolved directly in blood and need special transport structures known as Lipoproteins e.g. HDL, LDL, VLDL 

LIPOPROTEINS

Structure

• In Lipoproteins, Lipid is present towards the core surrounded by proteins in the periphery.

Lipids present in Lipoproteins

• Triglyceride ? NP
• Phospholipid ? Amphipathic
• Cholesterol ? Amphipathic
• Cholesterol ester (cholesterol + FA) ? NP
• Proteins are called Apo-proteins

Arrangement of lipids in Lipoprotein

• Non-polar Lipids (TG, Cholesterol ester)
  • Present embedded in core 
• Amphipathic Lipids (Cholesterol, phospholipids)
  • Polar portion will be towards outside
  • Non-polar portion will be towards inside

Composition of various lipoproteins

Lipoprotein	Lipid present	Protein/Apoprotein present
Chylomicron	TG (exogenous)	Apo B48
Chylomicron Remnant	TG + Cholesterol	Apo B48 + Apo E
VLDL	TG (endogenous)	Apo B100
VLDL Remnant (IDL)	TG + Cholesterol	Apo B100 + Apo E
LDL	Cholesterol	Apo B100 + Apo E
HDL	Cholesterol ester	Apo-A, Apo-C and Apo-E

Related Biochemistry Articles:

All Important Things About Carbohydrate Metabolism - NEET PG Biochemistry	Amino Acid Disorders - NEET PG Biochemistry	An easy approach to controversial questions in Biochemistry
Biochemistry FAQs answered by Dr. Smily Pruthi	Important Topics in Biochemistry for NEET-PG by Dr. Smily Pruthi	How to Prepare Biochemistry for Medical PG Entrance | PrepLadder
Important Topics in Biochemistry for AIIMS-PG by Dr. Smily Pruthi	Amino Acids (Basic, Acidic), Transamination & Proteins	Enzymes Classification, Properties - NEET PG Biochemistry

High Density Lipoproteins (HDL)

Functions

• HDL performs Reverse cholesterol Transport i.e. transport of excess cholesterol from peripheral tissues and blood vessels to Liver

How HDL adds Fatty acid

Important Information

• Exogenous TG is transported to peripheral tissues by Chylomicron.
• Endogenous TG is transported from liver to peripheral tissues by: VLDL
• Cholesterol is transported from liver to peripheral tissues by: LDL
• Cholesterol is transported from peripheral tissues to liver by: HDL 

Lipoprotein lipase

• Anabolic enzyme present in endothelium cells
• Breaks TG present in chylomicrons and VLDL to convert them to their remnants.

Ligands on lipoproteins for uptake by liver

• Ligands are proteins present on lipoprotein by which liver will recognise particular Lipoprotein

Hyperlipoproteinemia (Fredrickson classification)

Type	Defect	LP	TG	Ch	Common names
I	Lipoprotein Lipase Or Apo C-II defect	Chylo > VLDL	↑	Normal	Familial Hyperchylomicronemia
II a	LDL Receptor or Apo B100	↑ LDL	N	↑	Familial Hypercholesterolemia
II b	Unknown	↑ VLDL ↑ LDL	↑	↑	Familial combined hyperlipoproteinemia
III	apo E	↑ Chylo–remnant ↑ VLDL remnant	↑	↑	Broad β diseases / Dys β lipoproteinemia

Important Information 

Clinical Features recognition to tackle hyperlipoproteinemia related clinical questions

• Tendon xanthoma   ↑ Cholesterol
• Eruptive xanthoma  ↑ TG
• Palmar & Tubero eruptive xanthoma   ↑ Chylo-remnant & ↑ VLDL remnant
• Milky plasma  ↑ Chylomicrons
• Acute pain in abdomen   ↑ TG

Important Information 

Lipoprotein ‘x’ 

• Abnormal Lipoprotein found in two conditions:
  • LCAT deficiency
  • Cholestatic states 
• Rich in amphipathic lipids (PL & cholesterol)
• Poor in neutral lipids (TG & cholesterol ester)

FATTY ACID SYNTHESIS

Characteristics

• Anabolic pathway
• Occurs in cytoplasm
• Activated by Insulin

FA synthase complex

• Main enzyme and a multienzyme complex (6 enzyme activities)
• Dimer (composed of 2 identical subunits)

Important Information

Q. FA is synthesized from? 

Ans: Acetyl Co A and not malonyl CoA

• Because extra Carbon of Malonyl CoA is not getting added in newly synthesized FA
• 1^st enzyme carboxylase adds one CO₂ to form malonyl CoA but 2^nd enzyme FA synthase removes the CO₂. So, only CO₂ of acetyl CoA are used.
• But, Main Donor of carbon for fatty acid synthesis – Malonyl CoA

CITRATE SHUTTLE

• Used for the transport of Acetyl CoA from mitochondria to cytoplasm for fatty acid synthesis
• Provides two things for FA synthesis
  • Acetyl CoA
  • NADPH

KETONE BODY SYNTHESIS AND KETONE BODY UTILIZATION

Similarities

• Both are catabolic pathway
• Both occur in mitochondria
• Both are activated by glucagon and inhibited by insulin

Differences

• KB synthesis occurs only in Liver whereas KB utilization occurs in vital organs brain and heart & also in muscles but never occurs in liver.

Note: In the first step of KB utilization, high energy CoA is added without using ATP. So, the rule of business (i.e. activation using ATP) is not followed.

Important information

• Thiolase is a common enzyme for 4 lipid metabolic pathways
  • Ketone body synthesis
  • Ketone body utilization
  • Cholesterol synthesis
  • β-oxidation of FA
• Liver cannot use ketone bodies as it lacks Thiophorase.

Previous Year’s Question

Q. Active metabolite form in synthesis of fatty acid is? (AIIMS Nov 2017)

1. Acetyl CoA
2. Malonyl CoA
3. Stearate
4. Palmitate

Q. Major product of fatty acid synthesis is? (AIIMS Nov 2017)

1. Acetyl CoA
2. ATP
3. Citrate
4. Palmitate

Q. Which of the following is an essential fatty acid? (FMGE JUNE 2018) 

1. Citric acid 
2. Linoleic acid 
3. Stearic acid 
4. Palmitic acid

Q. Type I hyperlipoproteinemia is characterized by? (NEET Jan 2019)

1. Elevated LDL
2. Elevated HDL
3. Elevated lipoprotein lipase
4. Elevated chylomicrons.

Q. Ketone bodies are not utilized by? (JIPMER May 2019)

1. Brain
2. RBC
3. Heart
4. Skeletal muscle

Q. A patient has multiple tendon xanthomas. Serum cholesterol (398 mg/dl) & LDL (220 mg/dl) were found to be raised. Statins were given to this patient. What is the diagnosis? (NEET Sep 2021)

1. Lipoprotein lipase deficiency 
2. Familial hypercholesterolemia
3. Tangier’s disease
4. Huntington’s disease

Q. Eicosanoids are formed from? (INICET May 2022)

1. Arachidonic acid
2. Platelet aggregation
3. 4 fused rings
4. Arginine 

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