fatty acid (1).pptx

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The document summarizes de novo fatty acid synthesis. It occurs in the liver, kidney, adipose tissue, and lactating mammary gland. Enzymes are located in the cytosol. Acetyl CoA from the mitochondria is the starting material and is converted to malonyl CoA by acetyl CoA carboxylase in an ATP-dependent reaction. Fatty acid synthase complex then catalyzes sequential reactions to produce palmitate through seven cycles. Production is regulated by enzymes, metabolites, hormones, and diet.

$⦿ De novo synthesis of fatty acids occurs in liver, kidney, adipose tissue & lactating mammary gland. ⦿ Enzymes are located in cytosomal fraction of the cell. ⦿ It is called as extramitochondrial or cytoplasmic fatty acid synthase system.$

⦿ Major fatty acid synthesized de novo is
palmitic acid (16C saturated fatty acid).
⦿ It occurs in liver, adipose tissue, kidney, brain
& lactating mammary glands.
⦿ Acetyl CoA is the source of carbon atoms.

⦿ Every molecule of acetyl CoA delivered to
cytoplasm, one molecule of NADPH is
formed.
⦿ ATPsupplies energy.

⦿ Production of acetyl CoA & NADPH
⦿ Conversion of acetyl CoA to malonyl CoA
⦿ Reactions of fatty acid synthase complex.

⦿ Acetyl CoA is the starting material for de novo
synthesis of fatty acids.
⦿ Acetyl CoA is produced in the mitochondria by
the oxidation of pyruvate, fatty acids,
degradation of carbon skeleton of certain
amino acids & from ketone bodies.
⦿ Mitochondria 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 by
tricarboxylic acid transporter.
In cytosol it is cleaved by ATP citrate lyase to
liberate acetyl CoA & oxaloacetate.

Glucose
Oxaloacetate
Citrate
Mitochondrial
matrix
Pyruvate
Acetyl CoA
Citrate
Oxaloacetate
Amino
acids
FA
Pyruvate
carboxylase
PDH
Complex
Citrate
synthase
ADP+Pi
Acetyl CoA
ATP
CoASH
Citrate
lyase
MDH
NADH + H+
Pyruvate
NADPH + H+
HMP Shunt
CO2
NADP+
Malate
NAD+
Fatty acid
Cytosol
Transfer of acetyl CoA from mitochondria to cytosol
Malic enzyme

⦿ Acetyl CoA is carboxylated to malonyl CoA by
the enzyme acetyl CoA carboxylase.
⦿ This is an ATP-dependent reaction & requires
biotin for CO2fixation.

O
CH3 – C– SCoA
Acety CoA
ADP + Pi
O
-OOC– CH2 – C – SCoA
Malonyl CoA
Acetyl CoA carboxylase
CO2, ATP
Biotin

⦿ At the end of 7cycles, the fatty acid synthesis
is complete & a 16-carbon fully saturated fatty
acid-namely palmitate-bound to ACPis
produced.
⦿ The enzyme palmitoyl thioesterase separates
palmitate from fatty acid synthase.
⦿ This completes the synthesis of palmitate

⦿ The FAScomplex offers great efficiency that
is free from interference of other cellular
reactions for the synthesis of fatty acids.
⦿ There is a good coordination in the synthesis
of all enzymes of the FAS complex.

⦿ Fatty acid production is controlled by
enzymes, metabolites, end products,
hormones and dietary manipulations.
⦿ Acetyl CoA carboxylase:
⦿ This enzyme controls a committed step in
fatty acid synthesis.

⦿ Glucagon, epinephrine & norepinephrine
inactivate the enzyme by cAMP dependent
phosphorylation.

⦿ Insulin, dephosphorylates & activates the
enzyme.
⦿ Insulin promotes fatty acid synthesis while
glucagon inhibits.
⦿ Insulin stimulates tissue uptake of glucose &
conversion of pyruvate to acetyl CoA.

⦿ Consumption of high carbohydrate or fat-free
diet increases the synthesis of acetyl CoA
carboxylase & fatty acid synthase, which
promote fatty acid formation.
⦿ Fasting or high fat diet decreases fatty acid
production by reducing the synthesis of acetyl
CoA carboxylase & FAS.

⦿ The reducing equivalents for fatty acid
synthesis are provided by NADPH which
come either from citrate (acetyl CoA) .

The document summarizes key aspects of de novo fatty acid synthesis. It occurs in the cytosol of liver, adipose tissue, and lactating mammary glands. Acetyl-CoA is the starting material, which is transported from mitochondria to cytosol via citrate. The fatty acid synthase complex contains multiple enzymatic domains that catalyze the sequential additions of two-carbon units from malonyl-CoA to produce palmitate (C16). The process requires NADPH and ATP as cofactors. Fatty acid synthesis is regulated by enzymes, metabolites, hormones, and diet.

BIOSYNTHESIS OF FATTY ACIDSYESANNA

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This document summarizes the process of de novo fatty acid synthesis. It occurs in the cytosol of liver, kidney, adipose tissue, and lactating mammary glands. Acetyl-CoA is the starting material, which is transported from mitochondria to the cytosol via citrate. In the cytosol, fatty acid synthase complex catalyzes the reactions to produce palmitic acid (C16) through cycles of condensation, reduction, dehydration, and reduction. The process requires acetyl-CoA, malonyl-CoA, ATP, and NADPH as substrates and is regulated by enzymes and hormones.

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De novo fatty acid synthesis occurs in the cytosol of liver, adipose tissue, and lactating mammary glands. It is carried out by a fatty acid synthase complex, which is a multienzyme dimer. Each monomer contains domains for the seven reactions that elongate acetyl-CoA by two carbons each cycle to produce palmitate. Acetyl-CoA is carboxylated to malonyl-CoA to initiate fatty acid synthesis, while NADPH provides reducing equivalents. The process is regulated by enzymes, metabolites, hormones, and diet.

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The document summarizes the three main pathways of fatty acid biosynthesis: de novo synthesis, elongation, and desaturation. De novo synthesis occurs in the cytoplasm and synthesizes saturated fatty acids like palmitate from acetyl-CoA derived from glucose. Elongation adds two-carbon units in the endoplasmic reticulum and mitochondria to produce longer fatty acids. Desaturation introduces double bonds in the endoplasmic reticulum through fatty acid desaturase enzymes.

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1. Fatty acids are synthesized in the cytoplasm via fatty acid synthase from acetyl-CoA. The major fatty acid produced is palmitic acid. 2. Acetyl-CoA is transported from mitochondria to the cytoplasm as citrate by citrate transporters and cleaved by ATP citrate lyase to produce acetyl-CoA for fatty acid synthesis. 3. Fatty acid synthesis occurs via fatty acid synthase, a multi-enzyme complex. The first step is carboxylation of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase.

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Fatty acids stored as triglycerides in adipose tissue are mobilized through the action of hormones like glucagon. They are broken down into free fatty acids which enter cells and are converted to fatty acyl-CoA derivatives in the cytoplasm. The fatty acyl-CoAs then undergo beta-oxidation in the mitochondria to produce acetyl-CoA molecules, which enter the citric acid cycle to generate ATP through oxidative phosphorylation. Beta-oxidation occurs through repeated cycles of reactions that cleave two-carbon acetyl groups from the fatty acyl-CoA, producing NADH and FADH2 in the process.

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This document discusses fatty acid synthesis in the body. It begins by defining fatty acids and describing their roles in energy storage and as structural components of membranes. There are three systems for fatty acid synthesis: de novo synthesis in the cytoplasm, chain elongation in mitochondria, and chain elongation in microsomes. De novo synthesis occurs primarily in the liver and adipose tissues, starting from acetyl-CoA derived from glucose. This synthesis takes place in the cytoplasm and requires acetyl-CoA transport from mitochondria via citrate. The document then details the multi-step process of de novo fatty acid synthesis catalyzed by acetyl-CoA carboxylase and fatty acid synthase, and describes regulation of synthesis by products, hormones,

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This document summarizes the process of de novo fatty acid synthesis. It occurs predominantly in the liver, kidney, adipose tissue and lactating mammary glands. Acetyl-CoA and NADPH provide the building blocks, while fatty acid synthase complexes catalyze the reactions. Acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase. Fatty acid synthase then undergoes seven cycles of reactions to elongate the carbon chain by two carbons each time from malonyl-CoA. This results in the production of the 16-carbon saturated fatty acid palmitate.

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1. Biosynthesis of fatty acids begins with carboxylation of acetyl-CoA to form malonyl-CoA, using biotin as a prosthetic group and ATP as an energy source. 2. Fatty acid synthase then catalyzes the step-wise condensation of acetyl-CoA and malonyl-CoA units to form fatty acid chains, using NADPH as an electron donor. 3. Regulation of fatty acid synthesis occurs through phosphorylation/dephosphorylation of acetyl-CoA carboxylase by AMP-activated kinase and protein phosphatases, as well as feedback inhibition by fatty acid products.

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The document discusses triglyceride synthesis in different tissues. It states that in adipose tissue, dihydroxyacetone phosphate produced during glycolysis is the precursor for triglyceride synthesis since adipocytes lack glycerol kinase. This means adipocytes require glucose oxidation to store fatty acids as triglycerides. The document then discusses fatty acid synthesis and oxidation, noting the pathways occur in different cellular locations and use different carriers for intermediates.

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The document summarizes fat metabolism, including the digestion, transport, and breakdown of fats in the body. Fats are broken down into fatty acids and glycerol then transported to cells. In cells, fatty acids undergo beta-oxidation to break them into acetyl-CoA molecules to enter the Krebs cycle and generate ATP through oxidative phosphorylation. Beta-oxidation occurs in cycles, breaking off two carbon units at a time to produce acetyl-CoA, NADH, FADH2, and ATP. Unsaturated fats require special enzymes and regulation controls the process. Ketone bodies form when acetyl-CoA accumulates without enough carbohydrates for the Krebs cycle.

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fatty acid (1).pptx

1. Dr. Mukhtar Jama Nour, MBBS , MD

2. ⦿ De novo synthesis of fatty acids occurs in liver, kidney, adipose tissue & lactating mammary gland. ⦿ Enzymes are located in cytosomal fraction of the cell. ⦿ It is called as extramitochondrial or cytoplasmic fatty acid synthase system.

3. ⦿ Major fatty acid synthesized de novo is palmitic acid (16C saturated fatty acid). ⦿ It occurs in liver, adipose tissue, kidney, brain & lactating mammary glands. ⦿ Acetyl CoA is the source of carbon atoms.

4. ⦿ Every molecule of acetyl CoA delivered to cytoplasm, one molecule of NADPH is formed. ⦿ ATPsupplies energy.

5. ⦿ Production of acetyl CoA & NADPH ⦿ Conversion of acetyl CoA to malonyl CoA ⦿ Reactions of fatty acid synthase complex.

6. ⦿ Acetyl CoA is the starting material for de novo synthesis of fatty acids. ⦿ Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate, fatty acids, degradation of carbon skeleton of certain amino acids & from ketone bodies. ⦿ Mitochondria are not permeable to acetyl CoA.

7. ⦿ 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 by tricarboxylic acid transporter. In cytosol it is cleaved by ATP citrate lyase to liberate acetyl CoA & oxaloacetate.

8. Glucose Oxaloacetate Citrate Mitochondrial matrix Pyruvate Acetyl CoA Citrate Oxaloacetate Amino acids FA Pyruvate carboxylase PDH Complex Citrate synthase ADP+Pi Acetyl CoA ATP CoASH Citrate lyase MDH NADH + H+ Pyruvate NADPH + H+ HMP Shunt CO2 NADP+ Malate NAD+ Fatty acid Cytosol Transfer of acetyl CoA from mitochondria to cytosol Malic enzyme

9. ⦿ Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase. ⦿ This is an ATP-dependent reaction & requires biotin for CO2fixation.

10. O CH3 – C– SCoA Acety CoA ADP + Pi O -OOC– CH2 – C – SCoA Malonyl CoA Acetyl CoA carboxylase CO2, ATP Biotin

11. ⦿ At the end of 7cycles, the fatty acid synthesis is complete & a 16-carbon fully saturated fatty acid-namely palmitate-bound to ACPis produced. ⦿ The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase. ⦿ This completes the synthesis of palmitate

12. ⦿ The FAScomplex offers great efficiency that is free from interference of other cellular reactions for the synthesis of fatty acids. ⦿ There is a good coordination in the synthesis of all enzymes of the FAS complex.

13. ⦿ Fatty acid production is controlled by enzymes, metabolites, end products, hormones and dietary manipulations. ⦿ Acetyl CoA carboxylase: ⦿ This enzyme controls a committed step in fatty acid synthesis.

14. ⦿ Glucagon, epinephrine & norepinephrine inactivate the enzyme by cAMP dependent phosphorylation.

15. ⦿ Insulin, dephosphorylates & activates the enzyme. ⦿ Insulin promotes fatty acid synthesis while glucagon inhibits. ⦿ Insulin stimulates tissue uptake of glucose & conversion of pyruvate to acetyl CoA.

16. ⦿ Consumption of high carbohydrate or fat-free diet increases the synthesis of acetyl CoA carboxylase & fatty acid synthase, which promote fatty acid formation. ⦿ Fasting or high fat diet decreases fatty acid production by reducing the synthesis of acetyl CoA carboxylase & FAS.

17. ⦿ The reducing equivalents for fatty acid synthesis are provided by NADPH which come either from citrate (acetyl CoA) .

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