HK Technical Logo
Now, Download Notes/Question Paper more frequently in one click using HK Technical APP for android users.
Android application for B Pharmacy Notes
Fatty acid oxidation Biochemistry Colored Notes 2nd Semester B.Pharmacy ,BP203T Biochemistry,BPharmacy,Handwritten Notes,Important Exam Notes,BPharm 2nd Semester,

Fatty acid oxidation Biochemistry Colored Notes

B.Pharmacy, 2nd Semester, 2022 (2021-2022) -

  • Download
189 58 Report Dec 29, 2021

Fatty acid oxidation Biochemistry Colored Notes B.Pharmacy 2nd Semester 2022 (2021-2022) Previous Year's Question Papers/Notes Download - HK Technical PGIMS



More Related Content


Fatty acid oxidation Biochemistry Colored Notes

Biochemistry (BP203T) Colored Notes



BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 1
FATTY ACID OXIDATION
 The fatty acids in the body are mostly oxidized by -oxidation.
 -Oxidation may be defined as the oxidation of fatty acids on the -carbon atom.
 This results in the sequential removal of a two carbon fragment, acetyl CoA.
Stages and tissues of fatty acid oxidation
The -oxidation of fatty acids involves three stages:
I. Activation of fatty acids occurring in the cytosol
II. Transport of fatty acids into mitochondria
III. --Oxidation proper in the mitochondrial matrix.
 Fatty acids are oxidized by most of the tissues in the body. However, brain, erythrocytes
and adrenal medulla cannot utilize fatty acids for energy requirement.
I. Fatty acid activation
 Fatty acids are activated to acyl CoA by thiokinases or acyl CoA
synthetases.
 Three different thiokinasesTo activate long chain (10-20 carbon),
medium chain (4-12 carbon) and short chain (< 4 carbon) fatty acids.
 The reaction occurs in two steps and requires ATP, coenzyme A and Mg2+
.


 In the activation, two high energy phosphates are utilized, because ATP is
converted to pyrophosphate (PPi).
 The enzyme inorganic pyrophosphatase hydrolyses PPi to phosphate (Pi).
 The immediate elimination of PPi makes this reaction totally irreversible.
II. Transport of acyl CoA into mitochondria
 The inner mitochondrial membrane is impermeable to fatty acids.
 A specialized carnitine carrier system (carnitine shuttle) operates to
transport activated fatty acids from cytosol to the mitochondria.
 This occurs in four steps:
1. Acyl group of acyl CoA is transferred to carnitine ( -hydroxy -
trimethyl aminobutyrate), catalysed by carnitine acyltransferase I (present
on the outer surface of inner mitochondrial membrane).
2. The acyl-carnitine is transported across the membrane to mitochondrial
matrix by a specific carrier protein.
3. Carnitine acyl transferase II (found on the inner surface of inner
mitochondrial membrane) converts acyl-carnitine to acyl CoA.
4. The carnitine released returns to cytosol for reuse.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 2
 It should be noted that the coenzyme A used for activation is different from the one that
finally combines with fatty acid in the mitochondria to form acyl CoA. Thus, the cell has
two separate pools (cytosolic and mitochondrial) of coenzyme A.
Inhibitor of carnitine shuttle:
 Carnitine acyl transferase I is inhibited by malonyl CoA, a key metabolite
involved in fatty acid synthesis that occurs in cytosol.
 In other words, while the fatty acid synthesis is in progress (reflected by high
concentration of malonyl CoA), their oxidation does not occur because carnitine
shuttle is impaired.
III. -Oxidation proper
 Each cycle of -oxidation, liberating a two carbon unit-acetyl CoA, occurs in a sequence
of four reactions.
1. Oxidation: Acyl CoA undergoes dehydrogenation by an FAD-dependent
flavoenzyme, acyl CoA dehydrogenase. A double bond is formed between and
carbons (i.e., 2 and 3 carbons).
2. Hydration: Enoyl CoA hydratase brings about the hydration of the double bond to
form -hydroxyacyl CoA.
3. Oxidation: -Hydroxyacyl CoA dehydrogenase catalyses the second oxidation and
generates NADH. The product formed is -ketoacyl CoA.
4. Cleavage: The final reaction in -oxidation is the liberation of a 2 carbon fragment,
acetyl CoA from acyl CoA. This occurs by a thiolytic cleavage catalysed by -ketoacyl
CoA thiolase (or simply thiolase).
 The new acyl CoA, containing two carbons less than the original, reenters the -oxidation
cycle.
 The process continues till the fatty acid is completely oxidized.
The overall reaction for each cycle of -oxidation:


 The scheme of fatty acid oxidation discussed above corresponds to saturated (no double
bond) and even carbon fatty acids. This occurs most predominantly in biological system.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 3
Oxidation of palmitoyl CoA
 In the cytosol, Palmitic acid is activated to Palmitoyl CoA by the enzyme
thiolase.
 This Palmitoyl CoA is then transported to mitochondiral matrix by
Carnitine shuttle system.
 In the mitochondrial matrix, palmitoyl CoA undergoes 7 cycles of -
oxidation to yield 8 acetyl CoA.
 Acetyl CoA can enter citric acid cycle and get completely oxidized to CO2
and H2O.
 The summary of -oxidation of palmitoyl CoA is shown below:


Energetics of –oxidation
 The ultimate aim of fatty acid oxidation is to generate energy.
The energy obtained from the complete oxidation of palmitic acid
(16 carbon) is given in Table below:
Energetics of palmitic acid oxidation
Mechanism ATP yield

7 FADH2 [oxidized by ETC, each FADH2
gives 2 ATP]
14 (10.5)
7 NADH (oxidized by ETC, each NADH
liberates 3 ATP)
21 (17.5)

Oxidized by citric acid cycle, each acetyl
CoA provides 12 ATP
96 (80)
Total energy from one mole of
palmitoyl CoA
131 (108)
Energy utilized for activation
(formation of palmitoyl CoA)
–2
Net yield for one molecule of palmitate 129 (106)
Note: Values in brackets in red colour represent ATP synthesized as per P:O ratios of 2.5 for
NADH and 1.5 for FADH2.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 4
Formation and Utilization of Ketone Bodies
 The compounds namely acetone, acetoacetate and -hydroxybutyrate (or 3-
hydroxybutyrate) are known as ketone bodies.
 Only the first two are true ketones while -hydroxybutyrate does not possess a keto
group.
 Ketone bodies are water-soluble and energy yielding.
 Acetone, however, is an exception, because it cannot be metabolized.
Ketogenesis
 The synthesis of ketone bodies occurs in the liver.
 The enzymes for ketone body synthesis are located in the mitochondrial matrix.
 Acetyl CoA, formed by oxidation of fatty acids, pyruvate or some amino acids, is the
precursor for ketone bodies.
 Ketogenesis occurs through the following reactions:
1) Two moles of acetyl CoA condense to form acetoacetyl CoA.
 This reaction is catalysed by thiolase an enzyme involved in the final step of
oxidation.
 Acetoacetate synthesis is appropriately regarded as the reversal of thiolase
reaction of fatty acid oxidation.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 5
2) Acetoacetyl CoA combines with another molecule of acetyl CoA to produce
hydroxy methyl glutaryl CoA (HMG CoA).
 HMG CoA synthase, catalysing this reaction, regulates the synthesis of ketone
bodies.
3) HMG CoA lyase cleaves HMG CoA to produce acetoacetate and acetyl CoA.
4) Acetoacetate can undergo spontaneous decarboxylation to form acetone.
5) Acetoacetate can be reduced by a dehydrogenease to -hydroxybutyrate.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 6
Utilization of ketone bodies
 The ketone bodies are easily transported from the liver to various tissues because they
are water-soluble.
 The two ketone bodiesAcetoacetate and -hydroxybutyrate serve as important
sources of energy for the peripheral tissues such as skeletal muscle, cardiac muscle,
renal cortex etc.
 The tissues which lack mitochondria (e.g. erythrocytes) however, cannot utilize
ketone bodies.
 The production of ketone bodies and their utilization become more significant when
glucose is in short supply to the tissues, as observed in starvation, and diabetes
mellitus.
 During prolonged starvation, ketone bodies are the major fuel source for the brain
and other parts of CNS.
 It should be noted that the ability of the brain to utilize fatty acids for energy is very
limited.
 The ketone bodies can meet 50-70% of the brain’s energy needs. This is an adaptation
for the survival of the organism during the periods of food deprivation.
Reactions of ketone bodies:
 is first converted to acetoacetate (reversal of synthesis) and
metabolized.
 Acetoacetate is activated to acetoacetyl CoA by a mitochondrial enzyme
thiophorase.
 The coenzyme A is donated by succinyl CoA intermediate in citric acid cycle.
 Thiophorase is absent in liver because ketone bodies are not utilized by the liver.
 Thiolase cleaves acetoacetyl CoA to two moles of acetyl CoA.
Ketoacidosis
 Both acetoacetate and -hydroxybutyrate are strong acids.
 Increase in acetoacetate and -hydroxybutyrate concentration in blood would
cause acidosis.
 The carboxyl group has a pKa around 4. Therefore, the ketone bodies in the
blood dissociate and release H+
ions which lower the pH.
 Diabetic ketoacidosis is dangerous may result in coma, and even death, if not
treated.
 Ketosis due to starvation is not usually accompanied by ketoacidosis.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 7
Treatment of ketoacidosis
 Rapid treatment of diabetic ketoacidosis is required to correct the metabolic
abnormalities and the associated water and electrolyte imbalance.
 Administration of insulin is necessary to stimulate uptake of glucose by tissues and
inhibition of ketogenesis.
BIO De novo synthesis of fatty acids CIDS
 The dietary carbohydrates and amino acids, when consumed in excess, can be converted
to fatty acids and stored as triacylglycerols.
 De novo (new) synthesis of fatty acids occurs predominantly in liver, kidney, adipose
tissue and lactating mammary glands.
 The enzyme machinery for fatty acid production is located in the cytosomal fraction of
the cell.
 Acetyl CoA is the source of carbon atoms while NADPH provides the reducing
equivalents and ATP supplies energy for fatty acid formation.
 The fatty acid synthesis may be learnt in 3 stages:
I. Production of acetyl CoA and NADPH
II. Conversion of acetyl CoA to malonyl CoA
III. Reactions of fatty acid synthase complex.
I. Production of acetyl CoA and NADPH
 Acetyl CoA and NADPH are the prerequisites for fatty acid synthesis.
 Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate and fatty acids,
degradation of carbon skeleton of certain amino acids, and from ketone bodies.
 Mitochondria, however, are not permeable to acetyl CoA.
 An alternate or a bypass arrangement is made for the transfer of acetyl CoA to cytosol.
 Acetyl CoA condenses with oxaloacetate in mitochondria to form citrate.
 Citrate is freely transported to cytosol where it is cleaved by citrate lyase to liberate acetyl
CoA and oxaloacetate.
 Oxaloacetate in the cytosol is converted to malate
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 8
 Malic enzyme converts malate to pyruvate.
 NADPH and CO2 are generated in this reaction. Both of them are utilized for fatty acid
synthesis.
Advantages of coupled transport of acetyl CoA and NADPH :
 The transport of acetyl CoA from mitochondria to cytosol is coupled with the
cytosomal production of NADPH and CO2 which is highly advantageous to the cell
for optimum synthesis of fatty acids.
II. Formation of malonyl CoA
 Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA
carboxylase.
 This is an ATP-dependent reaction and requires biotin for CO2 fixation.
 The mechanism of action of acetyl CoA carboxylase is similar to that of
pyruvate carboxylase.
 Acetyl CoA carboxylase is a regulatory enzyme in fatty acid synthesis.
III. Reactions of fatty acid synthase complex
 The remaining reactions of fatty acid synthesis are catalysed by a
multifunctional enzyme known as fatty acid synthase (FAS) complex.
 In eukaryotic cells, including man, the fatty acid synthase exists as a dimer
with two identical units.
 Each monomer possesses the activities of seven different enzymes and an
acyl carrier protein (ACP) bound to 4c phosphopantetheine.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 9
 Fatty acid synthase functions as a single unit catalysing all the seven
reactions.
 Dissociation of the synthase complex results in loss of the enzyme activities.
 In the lower organisms (prokaryotes), the fatty acid synthesis is carried out by
a multi enzyme complex in association with a separate acyl carrier protein.
This is in contrast to eukaryotes where ACP is a part of fatty acid
synthase.
The sequence of reactions of the extra mitochondrial
synthesis of fatty acids (palmitate):
1. The two carbon fragment of acetyl CoA is transferred to ACP of fatty acid synthase,
catalysed by the enzyme acetyl CoA-ACP transacylase.
 The acetyl unit is then transferred from ACP to cysteine residue of the enzyme.
 Thus ACP site falls vacant.
2. The enzyme malonyl CoA-ACP transacylase transfers malonate from malonyl CoA to
bind to ACP.
3. The acetyl unit attached to cysteine is transferred to malonyl group (bound to ACP).
 The malonyl moiety loses CO2 which was added by acetyl CoA carboxylase.
 Thus, CO2 is never incorporated into fatty acid carbon chain.
 The decarboxylation is accompanied by loss of free energy which allows the
reaction to proceed
forward.
 This reaction is catalyzed by
4. reduces ketoacyl group to hydroxyacyl group.
 The reducing equivalents are supplied by NADPH.
5. undergoes dehydration.
 A molecule of water is eliminated and a double bond is introduced between and
carbons.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 10
6. A second NADPH-dependent reduction, catalysed by enoyl-ACP reductase occurs to
produce acyl-ACP. The four-carbon unit attached to ACP is butyryl group.
 The carbon chain attached to ACP is transferred to cysteine residue and the
reactions 2 to 6 are repeated 6 more times.
 Each time, the fatty acid chain is lengthened by a two-carbon unit (obtained from
malonyl CoA).
 At the end of 7 cycles, the fatty acid synthesis is complete and a 16-carbon fully
saturated fatty acid namely ⏟

produced. s
7. The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase.
 This completes the synthesis of palmitate.
Summary of palmitate synthesis
 Of the 16 carbons present in palmitate, only two come from acetyl CoA directly.
The remaining 14 are from malonyl CoA which, in turn, is produced by acetyl
CoA. The overall reaction of palmitate synthesis is summarized as:


Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 11
Some important pathways
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 12
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 13
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 14
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 15
Amino acid metabolism
 The amino acids undergo certain common reactions like transamination followed by
deamination for the liberation of ammonia.
 The amino group of the amino acids is utilized for the formation of urea which is an
excretory end product of protein metabolism.
 The carbon skeleton of the amino acids is first converted to keto acids (by transamination)
which meet one or more of the following fates.
1. Utilized to generate energy.
2. Used for the synthesis of glucose.
3. Diverted for the formation of fat or ketone bodies.
4. Involved in the production of non-essential amino acids.
TRANSAMINATION
 The transfer of an amino ( NH2) group from an amino acid to a keto acid is known as
transamination.
 This process involves the interconversion of a pair of amino acids and a pair of keto
acids, catalysed by a group of enzymes called transaminases (recently,
aminotransferases).
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 16
Salient features of transamination
1. All transaminases require pyridoxal phosphate (PLP), a coenzyme derived from vitamin B6.
2. Specific transaminases exist for each pair of amino and keto acids. However, only two
namely, aspartate transaminase and alanine.
 Transaminase  make a significant contribution for transamination.
3. There is no free NH3 liberated; only the transfer of amino group occurs.
4. Transamination is reversible.
5. Transamination is very important for the redistribution of amino groups and production of
non-essential amino acids, as per the requirement of the cell. It involves both catabolism
(degradation) and anabolism (synthesis) of amino acids.
6. Transamination diverts the excess amino acids towards energy generation.
7. The amino acids undergo transamination to finally concentrate nitrogen in glutamate.
Glutamate is the only amino acid that undergoes oxidative deamination to a significant extent to
liberate free NH3 for urea synthesis.
8. All amino acids except lysine, threonine, proline and hydroxyproline participate in
transamination.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 17
9. Transamination is not restricted to -amino groups only. For instance, G-amino group of
ornithine is transaminated.
10. Serum transaminases are important for diagnostic and prognostic purposes.
Mechanism of transamination
Transamination occurs in two stages:
1. Transfer of the amino group to the coenzyme pyridoxal phosphate (bound to the coenzyme) to
form pyridoxamine phosphate.
2. The amino group of pyridoxamine phosphate is then transferred to a keto acid to produce a
new amino acid and the enzyme with PLP is regenerated.
Figure: Mechanism of transamination (A) Involvement of
pyridoxal phosphate (PLP) in the transfer of amino group.
(B) Formation of enzyme PLP-Schiff base and amino acid-PLPSchiff base.
 Note that when the amino acid binds, enzyme
separates.
All the transaminases require pyridoxal phosphate (PLP) a derivative of vitamin B6.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 18
 The aldehyde group of PLP is linked with amino group of lysine residue, at the active site of
the enzyme forming a Schiff base (imine linkage).
 When an amino acid (substrate) comes in contact with the enzyme, it displaces lysine and
a new Schiff base linkage is formed.
 The amino acid-PLP-Schiff base tightly binds with the enzyme by non-covalent forces.
 Snell and Braustein proposed a Ping Pong Bi Bi mechanism involving a series of
intermediates (aldimines and ketimines) in transamination reaction.
DEAMINATION
 The removal of amino group from the amino acids as NH3 is deamination.
 Transamination involves only the shuffling of amino groups among the amino acids.
 On the other hand, deamination results in the liberation of ammonia for urea
synthesis.
 Simultaneously, the carbon skeleton of amino acids is converted to keto acids.
 Deamination may be either oxidative or non-oxidative.
 Although transamination and deamination are separately discussed, they occur
simultaneously, often involving glutamate as the central molecule. For this reason,
some authors use the term transdeamination while describing the reactions of
transamination and deamination, particularly involving glutamate.
I. Oxidative deamination:
 Oxidative deamination is the liberation of free ammonia from the amino group of amino
acids coupled with oxidation.
 This takes place mostly in liver and kidney.
 The purpose of oxidative deamination is to provide NH3 for urea synthesis and α -keto
acids for a different of reactions, including energy generation.
 Role of glutamate dehydrogenase: In the process of transamination, the amino
groups of most amino acids are transferred to α -ketoglutarate to produce
glutamate.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)
BP203T SHORT NOTE ON LIPID METABOLISM (CHAPTER 3)
HK Technical by Abdiyea 19
 Thus, glutamate serves as a ‘collection centre’ for amino groups in the
biological system.
 Glutamate rapidly undergoes oxidative deamination, catalysed by
glutamate dehydrogenase (GDH) to liberate ammonia.
 This enzyme is unique in that it can utilize either NAD+ or NADP+ as a
coenzyme. Conversion of glutamate to α-ketoglutarate occurs through the
formation of an intermediate, α-iminoglutarate.
 Glutamate dehydrogenase catalysed reaction is important as it reversibly
links up glutamate metabolism with TCA cycle through α-ketoglutarate.
GDH is involved in both catabolic and anabolic reactions.
Downloaded from HK Technical PGIMS (pgims.hktechnical.com)


Did you find, what you are looking for?
Yes
No

Find what you need faster with our free app!


In case, Feaures are not working on this website, please update your browser or use another browser. View Supported Browser List. Further if you think this is an error, please feel free to contact us at [email protected] or you may also Chat with us.


Copyright © 2021-23 HK Technical