metabolism protein and fat

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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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