DISCUSSION CLASS

DR. LEENA CHAND

ASSISTANT PROFESSOR
SRIHER
 ESSAY ……
1. Explain the steps of β-oxidation of Palmitic
acid. Add a note on the energetic and regulation
of the pathway.
2. Name the ketone bodies. Explain the process
of ketogenesis and ketolysis. mention 2
condition where ketone bodies are present in
urine
 SHORT ESSAYS…..
• Phospholipids
• Essential Fatty Acids
• Lipoproteins
• Digestion and absorption of Lipids
• Structure and function of Cholesterol.
• Bile acids, Bile salts
• VLDL metabolism
• HDL Metabolism
 Explain the steps of β-oxidation of Palmitic acid.
Add a note on the energetic and regulation of
the pathway.
Introduction : Triacylglycerols are the most aboudant storage
form of fat in adipose tissue& serve as a energy reserve of the
body
• FFA released by hydrolysis from triacylglycerol enter the
circulation. It enter different organ and are utilized as source of
energy
The purpose of oxidation of Fatty acid is to generate
energy
Site : all tissues , prominent in liver and skeletal muscle.
Intracellular location: mitochondria.
Substrate: fatty acids.
Product: acetyl CoA, NADH, FADH2
Steps in fatty acid oxidation
• Activation of fatty acids
• Transport of fatty acids across the
mitochondrial membranes into mitochondrial
matrix
• Beta oxidation of fatty acids
1. Activation of fatty acids
• FA are activated to fatty acyl CoA by acyl CoA synthase
(thiokinase) present in the cytoplasm
Fatty acid+ATP+CoA--->Acyl-CoA +PPi+AMP

2. Transport of fatty acids across the mitochondrial

membranes into mitochondrial matrix by Carnitine
shuttle
• Mitochondrial inner membrane is impermeable to
bulky polar molecules like CoA
3. Beta-Oxidation of Fatty Acids is
• A Repeated Sequence of 4 Reactions
Four enzymatic reactions:
• 1.Dehydrogenation between alpha and beta carbons (C2
and C3) in a FAD-linked reaction.
• 2.Hydration of the double bond by enoyl CoA hydratase.
• 3.A second dehydrogenation in a NAD-linked reaction.
• 4.Thiolytic cleavage of the thioester by beta-ketoacyl
CoAthiolase.
• This sequence of reactions is repeated until the fatty acyl
chain is completely degraded to acetyl CoA
 
Energitics
• Palmitic acid as an example
• From palmitoyl CoA to acetyl CoA: ATP
• Acyl CoA dehydrogenase 7 FADH2 10.5
• Beta-OH dehydrogenase 7 NADH 17.5
From 8 acetyl CoA 80
• Total energy yield 108
• ATP are used for activation of FA -2
• Hence net gain of ATP 106
Regulation of fatty acid oxidation
• CPT-1 is the regulator of entry of fatty acids into mitochondria.
Malonyl CoA inhibits CAT-I activity. Thus during fatty acid
synthesis, beta-oxidation is inhibited.
•  
Name the ketone bodies. Explain the process of ketogenesis and
ketolysis. mention 2 condition where ketone bodies are present
in urine

Introduction: Ketone bodies are produced from

acetyl-CoA, mainly in the mitochondrial matrix
of liver cells
Name :The three ketone bodies are
Acetoacetate, Beta- Hydroxy butyrate and
Acetone.
Conditions: starvation, diabetes
Ketogenesis- synthesis of ketone bodies
Organ : liver
Cellular site : mitochondria
• Acetone is highly volatile and is exhaled is
responsible for the characteristic "fruity"
odour of the breath of persons with diabetic
ketoacidosis.
• Beta-hydroxybutyrate and Acetoacetate are
transported from liver to the extrahepatic
tissues like muscle, brain or heart where are
utilized as fuel in place of glucose.
• Regulation of Ketogenesis
• CPT-I activity regulates the entry of long chain acyl
groups into mitochondria.
• Normal Level
• Normal KB in plasma: 0.2mmol/L
• Starvation : 3-5 mmol/L
• Diabetic ketoacidosis: >12mmol/L
• Normal KB in urine: <1mg/day
•  
• Identified by Rothera test of urine
• Conditions like - starvation & diabetes mellitus
• Starvation Ketoacidosis
Absence of intake of food

No stimuli from intestine to release insulin from

pancreas.

 Insulin & glucagon

Lipolysis & Oxidation of fatty acids

 
Ketoacidosis
 Diabetic ketoacidosis(DKA

• DKA is due to a marked deficiency of insulin with excess of

glucagon.
• In untreated diabetes, the concentration of ketone bodies in
blood increases so much that it decreases the pH of blood.
This condition is called “acidosis” which can lead to coma or
death.
• High concentration of ketone bodies in blood and urine is
referred as “ketosis”. Due to high concentration of
acetoacetate, which is converted to acetone, the breath and
urine of the untreated diabetic patients smells like acetone.
 Short essay…..
• Phospholipids
• Essential Fatty Acids
• Lipoproteins
• Digestion and absorption of Lipids
• Structure and function of Cholesterol.
• Bile acids, Bile salts
• VLDL metabolism
• HDL Metabolism
 Digestion and absorption of Lipids
Importance of Lipids –
• storage form of energy
• Necessary to meet requirements of fat solvable vitamins
• Requirements of essential fatty acids
Sources of lipids- cholesterol ester(2%), triacyl glycerol(98%),
phospholipid etc
Phases Of Lipid Digestion-
Preparatory phase, Transport phase, Transportation phase
There is no digestion of lipid in mouth except for neonate (lingual lipase
will digest short chain fatty acids)
Bile will do emulsification so increases surface area for better action of
enzymes
Enzymes help in digestion are – pancreatic lipase, colipase,
phospholipaseA2, cholesterol esterase.
Transport from intestine to different parts by lipoprotein (chylomicron)
Any defect in lipid digestion leads to – steatorrhea.
 Digestion and absorption of Lipids

• Dietary lipids are mainly in the form of –

triacylglycerols (98%), a small amount of
cholesterol esters and phospholipids
 Enzyme required
 Mouth – no digestion except baby ( lingual
lipase)
 Stomach – gastric lipase
 Intestine – bile help in emulsification
 Bile helps in emulsifing fat.
 It breaks apart the fat globules into fat droplets
 Also keep the droplets from reforming into globules.
 It keeps them in dissolved state.
• Pancreatic enzymes- co-lipase, lipase,
cholesterol esterase, phosppholipase A2
Digested lipids will move in the circulation with
the help of chylomicron.
Disorder – defect in digestion and absorption of
lipid leads to steatorrhea.
 Phospholipids

Defn : The Complex lipids having fatty acid, alcohol and phosphoric acid.
Types : Phospholipids are of two types depending upon the nature of
alcohols present in them
glycerophospholipids
sphingophospholipids.
Example : glycerophospholipids - Phosphatidic acid, Phosphatidyl choline
(Lecithin), Phosphatidyl inositol
sphingophospholipids. Sphingomyelin

Functions of phospholipids:
Phosphatidyl choline: Major constituent of plasma membrane-rendering
them semipermeable character. A constituent of surfactant; absence in
newborns results in respiratory distress syndrome
Phosphatidyl inositol: Forms second messengers- role in signal transduction
Sphingomyelin: Found in the membranes of myelin sheath.
 Structure and function of Cholesterol
• Structure:
• C27H46O
• Has one hydroxyl group at C3 and a double bond between C5 & C6
• Has a side chain of 5 methyl groups
• It is found in association with FA to form Cholesteryl ester
• It is insoluble in water and soluble in organic solvents such as chloroform,
benzene and ether
Functions:
• Component of cell membrane --modulator
• Insulation of nerve fibers
• Formation of bile acids which help in emulsification & digestion of fats
• Formation of steroid hormones
• Formation of vitamin D
• Help in neuronal connections in brain which help in learning and memory.
 Essential Fatty Acids
Defn : EFA are those fatty acids which are essential to the body, but cannot be
synthesized in the body and thus have to be supplemented in the diet. They are
Linoleic acid
Linolenic acid
Archidonic acids
Functions of Essential Fatty acids:
• Cause fluidity of membranes
• Arachidonic acid produces prostaglandins, thrombaxanes and
leukotrienes.
• Serve as precursors for signalling molecules involved in cell growth,
and development.
• PUFA are used for esterification and excretion of cholesterol
• Decrease LDL cholesterol and increase HDL cholesterol
• Has role in vision
EFA deficiency:
Dry skin , Scaly or flaky skin, Dry, lackluster, brittle hair, Dry eyes
 Lipoproteins

• Spherical macromolecular complexes.

• Help in the transport of TGL and cholesterol
through blood stream between various tissues.
• Lipoproteins consist of a core of
– Hydrophobic lipids (cholesterol ester & TGL).
– Surrounded by a shell of amphipathic lipids.
– (PL & free cholesterol) along with proteins.
 
• Lipoproteins are classified into five different types according to size and
density:
• Chylomicrons
• Very low density lipoprotein(VLDL)
• Intermediate density lipoprotein (IDL)
• Low density lipoprotein (LDL)
• High density lipoprotein (HDL)
• Cholesterol rich lipoproteins:
LDL
HDL
TGL rich lipoproteins:
Chylomicrons
VLDL
• Functions of lipoproteins
• Chylomicrons: transport cholesterol & TGL from
the intestine to the peripheral tissues
• VLDL: transport of TGL from the liver to the
peripheral tissues
• LDL: transport of cholesterol from the liver to the
peripheral tissues
• HDL: transport of cholesterol from the peripheral
tissues to the liver
 Formation of HDL
• Synthesized by liver and small intestine.
• Apo A, ApoC and apoE synthesized in liver are
transferred to HDL in plasma.
• Functions:
– Takes part in reverse cholesterol transport
– Acts as a repository for apoC and apoE required in
the metabolism of CM & VLDL.
 Reverse Cholesterol Transport (RCT)

Process whereby excess cholesterol in peripheral

cells, especially foam cells, is returned to the liver
for degradation into bile salts and excretion in bile.

Bile salts

CE
 Electron transport chain
• Sequence of complexes found in the inner mitochondrial membrane
• They accept e- from e- donors such as NADH or succinate, shuttle
these e- across the membrane creating an electrical & chemical
gradient
• Through the proton driven chemistry of the ATP synthase, generate
ATP
Consist of - Complexes I, II, III, and IV are proton pumps and complex
V as ATP synthase
Compositions -
•Complex I - NADH-Q oxidoreductase- FMN, Fe-S
•Complex II- Succinate Q reductase- FAD, Fe-S
•Complex III - Q-Cytochrome C oxidoreductase - Heme bH, Heme bL,
Heme C1, Fe-s
•Complex IV- Cytochrome c oxidase- Heme a, Heme a3, CuA & CuB
•ATP synthase
 Overview of electron flow through the respiratory chain
Succinate Fumarate

Complex II
Succinate-Q
reductase

NADH+H+ ½ O2+2H+

Q Cyt c

NAD H20
Complex I ComplexI II Complex IV
NADH-Q Q-cyt c Cyt c oxidase
oxidoreductase oxidoreductase
 Electron transport chain
• Four complexes are normally associated with
the electron transfer chain.
• Complex I - NADH dehydrogenase, also called
NADH Coenzyme Q reductase.
• Complex II - Succinate - Coenzyme Q
reductase.
• Complex III - Coenzyme Q - cytochrome c
reductase.
• Complex IV - Cytochrome c oxidase.
 Components of the complexes of electron
transport chain
• Flavoproteins: present in complexes I & II
(FMN & FAD to FMNH2 & FADH2). Take part in
two electron transfers.
• Iron-sulfur proteins (non-heme iron proteins,
Fe-S): present in complexes I,II and III. They
contain 1,2, or 4 Fe atoms linked to inorganic
sulfur atoms &/or vis Cys-SH groups to the
protein. Take part in single electron transfers.
Oxidative phosphorylation is comprised of the following
processes

1) Final conversion of reducing equivalents (NADH and

FADH2) generated from oxidation of fuel sources to ATP
2) Electron transfer through 3 protein assemblies (Complex
I, III, and IV) to O2
3) Transport of H+ out of the mitochondrial matrix
4) Transport of H+ into the mitochondrial matrix
5) Synthesis of ATP
 Flow of e- through respiratory chain complexes
4H+ 2H+ 4H+ 4H+
Intermembrane
space FAD
Cyt c Cyt c

Complex I Complex II
Inner
Mitochondrial FeS Cyt b Heme a+a3 Cyt b Q Fe-S
Q CuACuB Cyt c1
membrane FMN Cyt c1
Complex IV Complex III
FAD
Complex III
Fe-S
Mitochondrial
matrix
NADH+H+ NAD ETF Fumarate Succinate
1/2O2+2H+
H2O
Pyruvate FAD
TCA cycle
Ketone bodies

Acyl CoA