Extra mitochondrial lipogenesis Flashcards by joseph dizon

Acetyl CoA + Oxaloacetate

Citrate

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Derivation of Acetyl CoA

Glucose
Glycolysis
Forms pyruvate
Pyruvate goes inside mitochondria
Become pyruvate dehydrogenase complex
Acetyl CoA

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Enzyme used in pyruvate to acetyl coa

Pyruvate dehydrogenase

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Majority of acetyl CoA enters

Kreb cycle

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Enzyme that catalyze acetyl coa +oxalo actetate to form citrate

Citrate synthase

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Commited step in krebs

Acetyl coa + oxaloacetate to form citrate catalyze by citrate synthase

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Pero darating yung time na masyado ng madaming ATP, magkakaroon ng excess acetylo CoA

So sa halip naumasok sa krebs si citrate lalabas sya sa mitochondria by shuttle mechanism

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Splitting citrate into acetyl CoA and oxaloacetate

Citrate lyase

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So ang acetyl coa na lumabas sa mitochondria papauntang cytoplasm, pwede mo syang magamit sa?

Lipogenesis

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Reaction 1

Acetyl CoA (2carbon) + C02 to malonyl CoA (3 carbon )

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Reaction 1

Enzyme

Acetyl CoA carboxylase (commited enzyme)

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Reaction 1

Prosthetic group

Biotin

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Reaction 1

Type of reaction

C02 fixation reaction

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Reaction 1

Reaction process

Acetyl CoA combines with CO2 na nangagaling sa HCO3. CO2 combines with biotin at ang biotin ang mag ttra sfer ng CO2 sa acetyl CoA to form malonyl CoA

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Rate limiting step and repeating step

Reaction 1

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Reaction 1.1

Carboxylation of biotin

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ATP+ HCO3+biotin enzyme complex to

Carboxy Biotin Acetyl CoA carboxylae complex

Reaction 1.1 carboxylation of biotin

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Reactin 1.2

Transfer of carboxyl

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Acetyl CoA + biotin to malonyl Coa

Reaction 1.2
Enzyme

Acetyl CoA carboxylase

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Acetyl CoA + biotin to malonyl Coa

Reaction 1.2

Prosthetic group

Biotin or

Carboxy biotin acetyl coa carboxylase complex

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Binds to biotin

Removes biotin

Avidin

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Dahil sa avidin no intermediate acceptor of CO2 so

Rate limiting step doesnt take place

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Rate limiting step and committed step

Reaction 1

Reaction 1.2

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Regulate acetyl CoA carboxylase

Allosteric enzyme

Covalently regulated enzyme

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Inhibitors of acetyl CoA carboxylase and regulation

Palmitic acid Citrate Phosphorylation and dephosphorilation

Active form of acetyl CoA carboxylase is an aggregate of a

Protomer of acetyl coa carboxylase

Binds to an allosteric site in the enzyme that lead to inhibition of acetyl coa carboxylase

Palmitic acid

Causes aggregation and promotes lipogenesis

Citrate

Dephosphorylate the enzyme ACC and activate it

Insulin

Phosphorylate the enzyme ACC and deactivates it

Glucagon and epinephrine

Reaction 2 (ACP step)

Malonyl CoA + ACP-SH to malonyl Acyl Carrier Protein + CoASH

Reaction 2 Enzyme

Malonyl transacylase

ACP-SH

Fatty acid synthase complex

Both ACP and COA contain

Phospopantetheine group

Components of phosphopatntheine group

Phosphoric acid | Panthotenic acid

Vitamin B complex

Panthotenic acid

Panthotenic acid components

Beta alanine | Sulfhydryl group

Where fatty acid being elongated attaches

Sulfhydryl group

Attaches to the fatty acid synthetase enzyme complex

Acyl carrier protein or ACP

Attaches to an aterenic acid nucleotide

Coenzyme A or COA

Acetyl CoA activated

Acetate

Succinyl CoA activated

Succinate

Malonyl is attached to

Acyl carrier protein

Fatty acid syntethase enzyme complex made up of

2 polypetide chain

Fatty acid synthetase enzyme complex Each polypeptide chain

There are 7 enzymes

Fatty acid synthetase enzyme complex Each polypeptide chain has an

Acyl carrier protein | Sulfhydryl group

Fatty acid synthetase enzyme complex Malonyl binds only in the

Central sulfhydryl group

Fatty acid synthetase enzyme complex Sulfhydryl group which happens to be the side chain of the amino acid cysteine

Peripheral sulfhydryl group

Fatty acid synthetase enzyme complex 1st timer molecule which is acetyl coming from acetyl coa will bind to

Peripheral sulfhydryl group

Fatty acid synthetase enzyme complex Position of 7 enzyme systems in each polypeptide chain

69 position

Fatty acid synthetase enzyme complex 2 functional group

4 enzyme coming from the first polypeptide 3 enzyme from second polypeptide Once contains the ACP and other 1 contains sulfhydryl group

Reaction 3

1st Condensation step

Reaction 3 or 1st condensation step

``` Malonyl ACP (3carbon) + acetyl CoA (2carbon) to Acetacetyl ACP (4carbon) + CO2 (1carbon) ```

Reaction 3 Enzyme

Acetyl transacylase | Ketoacyl synthase

During condensation reaction

Add 2 carbon atoms

Reaction 3 Reaction process

Malonyl ACP combines with acetyl CoA = 5 carbons ( hindi naman pwede yung odd kaya) Release CO2 minus 1 That formed acetoacetyl ACP formed total 4 carbon

Reaction 4

Reduction step

Reaction 4 or reduction step

``` Acetoacetyl ACP (4carbon) to Beta hydroxyacyl ACP (4carbon) ```

Reaction 4 Enzyme

Ketoacyl reductase

Reaction 4 Reducing agent

NADPH Add electrons to the ketone group to become hydroxy group

Reaction 5

Dehydration step

Reaction 5 or dehydration step

Beta hydroxyacyl ACP (carbon) to | Alpha, Beta unsaturated Acyl- ACP (4carbon)

Reaction 5 Enzyme

Hydratase

Reaction 6

Reduction step part 2

Reaction 6 or reduction step part 2

Alpha, Beta unsaturated Acyl-ACP (4carbon) to | Butyryl -ACP (4carbon)

Reaction 6 Enzyme

Enoyl reductase

Reaction 6 Reducing agent

NADPH

Reaction 6 Butyryl ACP

Saturated Goes back to reaction 3

Cycling steps

``` Butyryl ACP (4carbon) + Malonyl ACP (3carbon) to ACyl-ACP (6carbon) + CO2 (1carbon) ```

Reaction 7

Release of fatty acid from the fatty acid synthase complex

Reaction 7 final step

Produce palmitic acid

Reaction 7

Deacylase (thioesterase)

Sources of NADPH

HMP shunt | Malic enzyme reaction

Malate to pyruvate Enzyme

NADP malate dehydrogenase | Oxidoreductase

Enzyme activity of malic enzyme

Oxidative decarboxylation reaction

Sphingomyelin catabolism Reaction 1

Sphingomyelin to ceramide + phophorylcholine

Sphingomyelin catabolism reaction 1 enzyme

Sphingomyelinase

Sphingomyelin catabolism reaction 2

Ceramide + phosphorylcholine to | Sphingosine + fatty acid

Sphingomyelin catabolism reaction 2 Enzyme

Ceramidase

How do you convert saturated fatty acid to unsaturated fatty acid?

Use desaturate enzymes and elongases

We can only introduce the double bond from

Carbon 9 down to carbon 1

Long chain saturated fatty acid + lysophosphoglyceride

Phopholipase A1

Unsaturated Fatty Acid + lysophophoglyceride

Phospholipase A2