metabolism protein and fat
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Metabolism of fat and protein is easier to learn if you take it as fun.TRANSCRIPT
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Dr. Daxaben N. MehtaPrincipal
Smt. S.C.U.Shah Home Science and C.U.Shah Arts & Commerce Mahila College
Wadhwancity – Dist: Surendranagar
METABOLISM OF FOOD
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AMINO ACID METABOLISM
ENVIRONMENT ORGANISM
Ingested protein
Bio- synthesis Protein
AMINO ACIDS
Nitrogen Carbon
skeletons
Urea
Degradation (required)
PurinesPyrimidinesPorphyrins
c c
Used for energy
pyruvateα-ketoglutaratesuccinyl-CoAfumarateoxaloacetate
acetoacetateacetyl CoA
(glucogenic)(ketogenic)
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TRANSAMINATION
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UREA CYCLE
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FAT METABOLISM
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Breakdown of fats into Acetyl coenzyme A --> Krebs CycleFADH2 --> Oxidative PhosphorylationNADH--> Oxidative PhosphorylationBreaks off two carbons at a time to acetyl CoARemaining goes another round
β - OXIDATION
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CH3CH2CH2CH2CH2COOH
[CH3CH2CH2CH2CH2CO-AMP]
CH3CH2CH2CH2CH2CO~SCoA
HS-CoA
Fatty acyl CoA
ATPPPi
AMP
Fatty acylCoA Ligase
Prepares a Fatty Acid for transport and metabolism
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Beta-Oxidation of Fatty Acids
In reaction 1, oxidation:• Removes H atoms from the
and carbons.• Forms a trans C=C bond.• Reduces FAD to FADH2.
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Beta-Oxidation of Fatty Acids
In reaction 2, hydration:• Adds water across the
trans C=C bond.• Forms a hydroxyl group
(—OH) on the carbon.
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Beta ()-Oxidation of Fatty Acids
In reaction 3, a second oxidation:
• Oxidizes the hydroxyl group.
• Forms a keto group on the carbon.
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Beta ()-Oxidation of Fatty Acids
In Reaction 4, acetyl CoA is cleaved:
• By splitting the bond between the and carbons.
• To form a shortened fatty acyl CoA that repeats steps 1 - 4 of -oxidation.
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CH3CH2CH2CH2CH2CO~SCoA
CH3CH2CH=CHCH2CO~SCoA
Fatty Acyl CoAFAD FADH
Fatty Acyl Dehydrogenase
CH3CH2CH2CHCH2CO~SCoA
OHEnoyl Co. A Hydratase
β Enoyl Co. A
β Hydroxy Acyl Co. A
β Keto Acyl Co. A
H2O
CH3CH2CH2CCH2CO~SCoA
ONAD+
NADH
β Hydroxy acyl Co. A Dehydrogenase
CH3CH2CH2CO~SCoA CH2CO~SCoAFatty Acyl CoA Acetyl CoA
ThiolaseHSCo A
MECHANISM
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CH3CH2CH2CH2CH2CH2CH2C~SCoA
O
CH3C~SCoA
O
CH3C~SCoA
O
CH3C~SCoA
O
Beta Oxidation
6 carbon Fatty Acid Acyl-CoA
3 two carbon Acetyl-CoAs
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ENERGY PRODUCTIONCOMPARISON BETWEEN
Hexanoic Acid C6H12O2 Glucose C6H12O6
Hexanoic acid Glucose Hexanoil Co. A - 1 ATP Pyruvate 2 ATP 6 NADHHexanoil Co. A Pyruvate 3 Acetyl-CoA 36 ATP 2 Acetyl-CoA 24 ATP2 FADH2 4 ATP2 NADH + H+ 6 ATP 2 NADH + H+ 6 ATP 45 ATP 38 ATP MW 116 MW 180 ATP per Gram 0.32 ATP per Gram 0.17
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Oxidation of Unsaturated Fatty Acids.
• Oxidation of monounsaturated fatty acyl-CoA requires additional reaction performed with the help of the enzyme isomerase.
• Double bonds in the unsaturated fatty acids are in the cis configuration and cannot be acted upon by enoyl-CoA hydratase (the enzyme catalyzing the addition of water to the trans double bond generated during β-oxidation.
• Enoyl-CoA isomerase repositions the double bond, converting the cis isomer to trans isomer, a normal intermediate in β-oxidation.
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Oxidation of polyunsaturated fatty acids.
• Requires two additional reactions and a second enzyme, reductase, in addition to isomerase.
• NADPH-dependent 2,4-dienoyl-CoA reductase converts trans-2, cis-4-dienoyl-CoA intermediate into the trans-2-enoyl-CoA substrate necessary for β-oxidation.
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Oxidation of odd-chain fatty acids.
• Odd-carbon fatty acids are oxidized by the same pathway as even-carbon acids until three-carbon propionyl-CoA is formed.
• After that, three additional reactions are required involving three enzymes.
• Propionyl-CoA is carboxylated by propionyl-CoA carboxylase (with the cofactor biotin) to form the D stereoisomer of methylmalonyl-CoA (The formation of the carboxybiotin intermediate requires energy from ATP).
• D-methylmalonyl-CoA is changed into L-methylmalonyl-CoA by methylmalonyl-CoA epimerase.
• L-methylmalonyl-CoA undergoes an intramolecular rearrangment to form succinyl-CoA, which enters the citric acid cycle. This rearrangment is catalyzed by methylmalonyl-CoA mutase, which requires coenzyme B12, derived from vitamin B12 (cobalamin).
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Ketone Bodies
A special source of fuel and energy for certain tissues • Some of the acetyl-CoA produced by fatty acid
oxidation in liver mitochondria is converted to acetone, acetoacetate and -hydroxybutyrate
• These are called "ketone bodies"• Source of fuel for brain, heart and muscle • Major energy source for brain during starvation • Synthesis in Figure 24.28 • They are transportable forms of fatty acids!
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Ketone Bodies and Diabetes
"Starvation of cells in the midst of plenty"• Glucose is abundant in blood, but uptake by cells in
muscle, liver, and adipose cells is low • Cells, metabolically starved, turn to gluconeogenesis
and fat/protein catabolism • In type I diabetics, OAA is low, due to excess
gluconeogenesis, so Ac-CoA from fat/protein catabolism does not go to TCA, but rather to ketone body production
• Acetone can be detected on breath of type I diabetics
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Connection to Krebs Cycle
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