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TCA regulation and Fat metabolism
ketogenesis, fatty acid synthesis, beta oxidation, tca regulation
15
Medical
Graduate
09/09/2009

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Term
TCA Regulation
Definition

1. Allosterically modified

2. Inhibited by ATP, Succinyl-CoA, NADH, Citrate

3. Activated by ADP, Ca2+, NAD+

4. Substrate (TCA intermediates) limit flux through the cycle

Term

Pathways for moving cytosolic NADH into the Mitochondria

(slow, General info)

Definition

1. Malate-Aspartate shuttle

2. Involves 2 anitporter carriers (Glutamate/aspartate and Malate/α-ketogluterate)

3. Involves 2 enzymes Malate dehydrongenase and aspartate aminotransferase

Term

Pathways for moving cytosolic NADH into the Mitochondria

(slow, step-by-step 6)

Definition

1. In cytosol, oxaloacetate --> malate by malate dehydrogenase and NADH

2. Malate through transporter

3. Malate back to Oxaloacetate, make NADH

4. Oxaloacetaate--> aspartate becasue glutamate -->

α-ketogluterate

5. Aspartate back to cytosol via transporter

6. Aspartate-->oxaloacetate because α-ketogluterate--> Glutamate

Term

Pathways for moving cytosolic NADH into the Mitochondria

(fast)

Definition

1. NADH, reduces dihydroxyacetonephosphate

->glycerol 3-phos by c. glyerol-3P dehydrogenase

2. Step one is reversed by  m. glycerol-3P dehydrogenase (like complex 2) FADH2 produced, e- transfer to ubiquinone

Term
Synthesis of triglycerol
Definition

1. dihydroxyacetonephosphate-> glycerol 3P

2. add 1 then another fatty acid chain from acyl-CoA to C 1&2(by acyl transferase)

3. remove P and add 3rd fattyacid chian from acyl-CoA

Term
Fatty acyl-CoA synthetase
Definition

1. first add AMP to fatty acid

2. then add CoA, AMP leaving grp

3. get PPi and Acyl-CoA

4. drive forward rxn by removing (using) PPi

Term

Fatty acids moved into Mitochondria

and it inhibition

Definition

1. Carnitine shuttle

2. Acyl-CoA +Carnitine--> CoA + acyl-carnitine By caritine acyl transferase 1

3. move into matirx

4. CoA + acyl-carnitine --> Acyl-CoA +Carnitine, by acyl carn. transferase 2

5. inhibited by malonyl-CoA (need to syn fatty acids)

Term
beta-oxidation
Definition

1. acyl-CoA dehydrogenase(bound to inner mebrane in e- chian give e- to Q) make trans double bond between C 2&3 make FADH2

2. enoyl-CoA hydratase add water across double bond

3. hydroxyacyl-CoA dehydrogenase oxidize hydorxyl to ketone make NADH

4. thiolase add CoA to new carbonly carbon --> acetyl-CoA and new shorter acyl-CoA

Term
beta-oxidation of CIS unsaturated fatty acid
Definition
1. enoyl-CoA isomerase to put double bond in right place (between C 2&3) and in right configuration TRANS
Term
beta oxidation of odd numbered fatty acid chains
Definition

1. Propionyl CoA formed (3C)

2. through several rxns converted to Succinyl-CoA

Term
Ketogenesis
Definition

1. thiolase add to acetyl-CoA, one Co-A released

2. HMG-CoA synthase add H2O form hydroxyl, and 3rd acetyl-CoA, 1 CoA released

3. HMG-CoA lyase remove acetyl-CoA and oxidize to carboxyl(acetoacetate)

4.  Hydroxybuterate dehydrogenase reduce to hydorxy acetoacetate-> hydroxybuterate

Term
Breakdown of Ketone bodies
Definition

1. liver lacks 2nd enzyme

2. hydroxybuterate -> acetoacetate, make NADH

HB dehydrogenase

3. β-ketoacyl-CoA trasnferase adds CoA from succinyl-CoA to acetoacetate-> acetoacetyl-CoA

4. thiolase splits acetoacetyl-CoA,

acetoacetyl-CoA+ Co-A-->2 aCoA

Term
shuttle Acetyl-CoA
Definition

1. uses several TCA steps

2. aCoA+oxaloacetate--> citrate

3. citrate to cytosol

4. citrate--> oxaloacetate+aCoA (use ATP)

5. Oxaloacetate-->malate (to mito.) OR malate-> pyruvate to mito.

6. malate/pyruvate(add CO2) --> oxaloacetate

Term
formation of malonyl-CoA
Definition

1. commited step of fatty acid syn

2. need biotin prosthetic group

3. add HCO3(CO2) to aCoA

4. by aCoA carboxylase

Term
fatty acid synthase
Definition

1. first adds mCoA to aCOA, then adds mCoA to growing acylCoA

2. acetyl and malonyl transfered to -S of f.a.synthase

3. acetly replaces term CO2

4. NADPH reduces carboxyl

5. water leaves, form double bond

6. NADPH reduces double bond

7. repeate, repeate, repeate

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