Cholesterol Synthesis Flashcards

1
Q

HMG-CoA Synthase

A

AcetoAcetyl CoA + Acetyl CoA +H2O-> 3-Hydroxy-3-methylglutary CoA
-lose CoA of Acetyl CoA

HMG
-used to synthesize cholesterol and ketone bodies

Two Isozymes of HMG CoA Synthase:

  • Cytoplasm- to synthesize Cholesterol
  • Mitochondria-To synthesize Ketone Bodies
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2
Q

HMG-CoA Reductase

A

Committed Step in Cholesterol Synthesis

Integral membrane protein of ER

  • catalytic domain projects into cytoplasm
  • reactions occur in cytoplasm

HMG-CoA-> Mevalonate (6C)
-Coenzyme: NADPH oxidized to NADP+

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3
Q

Mevalonate-> IPP

A

Mevalonate-> 3-isopentenyl pyrophosphate
3. Kinase-5-Phosphate-mevalonate
4. Kinase- 5-Pyrophosphate-mevalonate
5. Kinase-OH phosphorylated
decarboxylase-releasing CO2 and forming double bond to for 3-isopentenyl pyrophosphate (IPP)

*6 MOLECULES OF IPP ARE USED TO SYNTHESIZE CHOLESTEROL

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4
Q

IPP-> DPP

A

IPP-> 3,3-Dimethylallylpyrophosphate (DPP)

Isomerase

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5
Q

Geranyl Transferase

A

7th step:
Catalyzes a series of transferase reactions using 5C substrates
C5-> C10/ Geranyl-> C15->Farnesyl

DPP+ IPP->GPP- Geranyl (10C)
GPP + IPP-> FPP-farnesyl (15C)

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6
Q

Squalene Synthase

A

8th step

FPP + FPP-> Squalene(30C)

  • two FPP molecules connect tail to tail
  • NADPH oxidized to NADP+
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7
Q

Squalene Monooxygenase

A

9th Step
Squalene->Squalene Epoxide
-requires molecular oxygen: O2-H2O
-coenzyme: NADPH oxidized to NADP+

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8
Q

Oxidosqualene cyclase

A

10th step
Squalene Epoxide->Lanosterol

complex multistep reaction leading to ring closure
-enzyme holds molecule in appropriate orientation for ring closure

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9
Q

SLOS

A

Smith-Lemli-Optiz syndrome
Due to deficiency of
-7-dehydrocholesterol-7-reductase
-enzyme involved in migration of the double bond

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10
Q

Sources of Cholesterol

A

Diet

De novo synthesis

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11
Q

Regulation of Cholesterol Synthesis

A

Tightly regulated by:

Primary control point:
3-hydroxy-3-methylglutary CoA reductase

Methods/Levels of Regulation:

  • Transcription of HMG-CoA reductase mRNA
  • Translation of HMG-CoA reductase protein
  • Degradation of HMG-CoA reductase
  • Phosphorylation of HMG-CoA reductase
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12
Q

Orientation of Hydroxyl and Double bond in Cholesterol?

A

Hydroxyl Orientation:
3 Beta-hydroxyl is below the plane of steroid nucleus
3-alpha-hydroxyl is above the plain of steroid nucleus

Double bond Orientation:
Cis:
-C5 hydrogen is beta
-Found in bile salts
-buckled structure

Trans:

  • C5 hydrogen is alpha
  • found in steroid hormones
  • Planar structure
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