Step 1 of Cholesterol Synthesis: 3 Acetyl CoA (2c) to _______ Occurs in ________ acetyl CoA trasnported from mitchochondria by _______ Catalysed by ___________ which is the rate limiting step

Step 1 of Cholesterol Synthesis: 3 Acetyl CoA (2c) to _Mevalonate_ Occurs in _Cytoplasm_ acetyl CoA trasnported from mitchochondria by _Citrate Shuttle_ Catalysed by _HMG CoA Reductase_ which is rate limiting

Enzyme responsible for rate-limiting step in Cholesotorl Synthesis: ___________________ phosphorylation by cAMP-dependent protein kinases __________ the enzyme (reversed by phosphatases) High cholesterol reduces levels of enzyme t1/2 and reduces levels of the enzyme's RNA

Enzyme responsible for rate-limiting step in Cholesotorl Synthesis: _HMG-CoA Reductase_ phosphorylation by cAMP-dependent protein kinases _inactivates_ the enzyme (reversed by phosphatases) High cholesterol reduces levels of enzyme t1/2 and reduces levels of the enzyme's RNA

Step 2 of Cholesterol Synthesis: 6C Mevalonate is converted to 5C _____________ by decarboxylation This molecule is an important intermediary for other molecules, including those in the _________

Step 2 of Cholesterol Synthesis: 6C Mevalonate is converted to 5C _Isopentenyl Pyrophosphate_ by carboxylation This molecule is an important intermediary for other molecules, including those in the ETC

Step 3 of Cholesterol Synthesis: _#_ of (5C) Isopentenyl Pyrophospahte units are converted to ___________(#C)_ Isopentenyl Pyrophosphate--\> Geranyl Pyrophosphate--\> Farnesyl Pyrophosphate--\>Squaline

Step 3 of Cholesterol Synthesis: _#_ of (5C) IPP units is converted to _Squaline (30C)_ Isopentenyl Pyrophosphate (5C) --\> Geranyl Pyrophosphate (10C) --\> Farnesyl Pyrophosphate (15C) X2--\> Squaline

Step 4 Cholesterol Synthesis: Squalene undergoes multiple enzyme catalyzed _________ reactions to yield lanosterol Lanosterol goes through 19 step reaction, _________ is formed

Step 4 Cholesterol Synthesis: Squalene undergoes multiple enzyme-catalyzed _Cyclicization_ reactions to yield lanosterol Lanosterol goes through 19 step reaction, _Cholesterol_ is formed

_____________: Polar carboxylic acid derivatives of cholesterol amphipathic molecules (biological detergents) Emulsification of ingested fats in duodenum synthesised in _____ and stored in ________ _____ % is excreted in faeces and remainder reabsorbed and recycled to liver

_Bile Salts_: Polar carboxylic acid derivatives of cholesterol amphipathic molecules (biological detergents) Emulsification of ingested fats in the duodenum synthesisedin _Liver_ and stored in _Gall Bladder_ _5-10%_ is excreted in feces and remainder reabsorbed and recycled to liver

______________ Acid: Derived from C20 essential ω6 PUFA C20:4 Incorporated into membrane glycerophospholipids Exert its actions by binding to specific plasma membrane receptors Functions as__________ ___________ molecule and plays important role in _________ and _________

_Arachonic Acid_: Derived from C20 essential ω6 PUFA C20:4 Incorporated into membrane glycerophospholipids Exert its actions by binding to specific plasma membrane receptors Functions as a L_ocal_ S_ignaling_ molecule and plays important role in _Inflammation_ and _Thrombosis_

Lecture 14: chol and phospholipid metabolism Flashcards by Jackson Barrett

Cholesterol Synthesis occurs mainly in ____, Intestin, and ______ ______

Cholesterol Synthesis occurs mainly in Liver, Intestine, and Gonads/Adrenals

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Cholesterol synthesis starts in _____ and is completed in ____

Cholesterol synthesis starts in Cytosol and is completed in Rough ER

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Step 1 of Cholesterol Synthesis:

3 Acetyl CoA (2c) to _______
Occurs in ________
- acetyl CoA trasnported from mitchochondria by _______
Catalysed by ________\_ which is the rate limiting step

Step 1 of Cholesterol Synthesis:

3 Acetyl CoA (2c) to Mevalonate
Occurs in Cytoplasm
- acetyl CoA trasnported from mitchochondria by Citrate Shuttle
Catalysed by HMG CoA Reductase which is rate limiting

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Enzyme responsible for rate-limiting step in Cholesotorl Synthesis: ________________\_

phosphorylation by cAMP-dependent protein kinases __________ the enzyme (reversed by phosphatases)
High cholesterol reduces levels of enzyme t_1/2and reduces levels of the enzyme’s RNA

Enzyme responsible for rate-limiting step in Cholesotorl Synthesis: HMG-CoA Reductase

phosphorylation by cAMP-dependent protein kinases inactivates the enzyme (reversed by phosphatases)
High cholesterol reduces levels of enzyme t_1/2and reduces levels of the enzyme’s RNA

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__________ are cholesterol-lowering drugs that act as transition-state analogs, binding like transition states to the HMG-CoA reductase.

Statins are cholesterol-lowering drugs that act as transition-state analogs, binding like transition states to the HMG-CoA reductase

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Step 2 of Cholesterol Synthesis:

6C Mevalonate is converted to 5C _____________ by decarboxylation
This molecule is an important intermediary for other molecules, including those in the _________

Step 2 of Cholesterol Synthesis:

6C Mevalonate is converted to 5C Isopentenyl Pyrophosphate by carboxylation
This molecule is an important intermediary for other molecules, including those in the ETC

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Step 3 of Cholesterol Synthesis: # of (5C) Isopentenyl Pyrophospahte units are converted to __________(#C)

Isopentenyl Pyrophosphate–> Geranyl Pyrophosphate–> Farnesyl Pyrophosphate–>Squaline

Step 3 of Cholesterol Synthesis:

# of (5C) IPP units is converted to Squaline (30C)
Isopentenyl Pyrophosphate (5C) –> Geranyl Pyrophosphate (10C) –> Farnesyl Pyrophosphate (15C) X2–> Squaline

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Step 4 Cholesterol Synthesis:

Squalene undergoes multiple enzyme catalyzed _________ reactions to yield lanosterol
Lanosterol goes through 19 step reaction, _________ is formed

Step 4 Cholesterol Synthesis:

Squalene undergoes multiple enzyme-catalyzed Cyclicization reactions to yield lanosterol
Lanosterol goes through 19 step reaction, Cholesterol is formed

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HMG CoA Reductase is ________ in the presence of a lot of cholestorol

HMG CoA Reductase is downregulated in the presence of a lot of cholesterol

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Formation of __________ from cholesterol represents the only pathway for cholesterol elimination from the body

Formation of Bile Salts from cholesterol represents the only pathway for cholesterol elimination from the body

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_____________:

Polar carboxylic acid derivatives of cholesterol
amphipathic molecules (biological detergents)
Emulsification of ingested fats in duodenum
synthesised in _____ and stored in ________
_____ % is excreted in faeces and remainder reabsorbed and recycled to liver

Bile Salts:

Polar carboxylic acid derivatives of cholesterol
amphipathic molecules (biological detergents)
Emulsification of ingested fats in the duodenum
synthesisedin Liver and stored in Gall Bladder
5-10% is excreted in feces and remainder reabsorbed and recycled to liver

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Deooxyxholic Acid is a ____________ and yeilds the ____________ GLycocholic Acid and Taurocholic acid

Deoxycholic Acid is a Bile Acid and yeilds the Bile Salts GLycocholic Acid and Taurocholic Acid

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___\_ fatty acids are precursors of prostaglandins, thromboxanes, and leukotrienes. They are _____-_inflammatory

ω6 fatty acids are precursors of prostaglandins, thromboxanes, and leukotrienes. They are Pro-inflammatory

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____\_fatty acids are cardioprotective, __\_-inflammatory, and ___________\_

ω3 fatty acids are cardioprotective, anti-inflammatory, and anticarcinogenic

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___________\_ Acid:

Derived from C20 essential ω6 PUFA C20:4
Incorporated into membrane glycerophospholipids
Exert its actions by binding to specific plasma membrane receptors
Functions as__________ ___________ molecule and plays important role in _________ and _________

Arachonic Acid:

Derived from C20 essential ω6 PUFA C20:4
Incorporated into membrane glycerophospholipids
Exert its actions by binding to specific plasma membrane receptors
Functions as a Local Signaling molecule and plays important role in Inflammation and Thrombosis

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___________ are formed from arachidonate oxidation and cyclization in ER

Prostaglandins are formed from arachidonate by oxidation and cyclization in ER

Thromboxanes synthesized from _____\_ by thromboxane synthase

Thromboxanes synthesized from PGH₂ by thromboxane synthase

___________: The most widely NSAID used medications in world

Is an ___________ inhibitor of COX1 and modifies activity of COX2
Downregulates ___________ pathway and lessens risk of thrombosis

Aspirin (Acetylsalicylate): The most widely NSAID used medication in the world

Is an Irreversible inhibitor of COX1 and modifies the activity of COX2
Downregulates Prostaglandin pathway and lessens the risk of thrombosis

Simplest GlyceroPhospholipid (GPL) is _______

Simplest GlyceroPhospholipid (GPL) is Phosphatidate

GlyceroPhospholipid (GPL) Structure

What is Phosphatidylinositol important for?

Broken into Diaglyerol which activates _________ and Inositol which releases ____________

Important for Cell Signaling.

Broken into Diaglyerol which activates Protein Kinase C and Inositol which releases Ca_²⁺ from the Endoplasmic Reticulum

Sphingolipids are components of all membranes but are particularly abundant in the ______\_

Sphingolipids are components of all membranes but are particularly abundant in the myelin sheath

_______________________\_ have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, necrosis, inflammation, senescence, and differentiation

Sphingolipid metabolites(eg. ceramide and sphingosine) have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, necrosis, inflammation, senescence, and differentiation

Sphingosine+ 1 FA = ________

Sphingosine+ 1 FA = ceramide

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are ceramides with one or more added sugars: * Particularly abundant in nerve cell membranes

_Glycosphingolipids_ are ceramides with one or more added sugars: * Particularly abundant in nerve cell membranes

Ceramide with one added sugar?

_C__erebrosides_

Ceramides with more than 1 sugar (not including sialic acid, NANA)

_Globoside_

Ceramide with 3 or more sugars (one of which is sialic acid, NANA)

_Ganglioside_

Glycosphingolipid Breakdown * Occurs mainly in \_\_\_\_\_\_\_\_ * Most active in ________ tissues * Enzyme deficiency causes the accumulation of intermediates that results in \_\_\_\_\_\_\_\_\_ * Known as sphingolipidoses, lysosomal storage diseases or lipid storage diseases

Glycosphingolipid Breakdown * Occurs mainly in _Lysosomes_ * Most active in _Neural_ tissues * Enzyme deficiency causes the accumulation of intermediates that results in _Cell Death_ * Known as sphingolipidoses, lysosomal storage diseases or lipid storage diseases

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Disease: * Failure of Glycosphingolipid breakdown * Deficiency of ß-hexosaminidase A activity and the lysosomal accumulation of GM2 gangliosides * Autosomal recessive disorder 1 in 30,000 in the general population, much higher (10-20X) in some ethnic groups: * _\_\_\_\_\_\_\_\__, _\_\_\_\_\_\_\_\_\_\_\__, _\_\_\_\_\_\_\_\_\_\_\_\_\_\_\__ * 3 clinical subtypes (associated with particular mutations) * infantile (progressive neurological degeneration, blindness, death by age 3) * juvenile * adult

_Tay Sachs_ _Disease_: * Failure of Glycosphingolipid breakdown * Deficiency of ß-hexosaminidase A activity and the lysosomal accumulation of GM2 gangliosides * Autosomal recessive disorder 1 in 30,000 in the general population, much higher (10-20X) in some ethnic groups: * _Ashkenazi jews_, _French-Canadian_, _Louisiana Cajuns_ * 3 clinical subtypes (associated with particular mutations) * infantile (progressive neurological degeneration, blindness, death by age 3) * juvenile * adult

\_\_\_\_\_\_\_\_\_\_\_\_\_ Disease: * Failure of Glycosphingolipid breakdown * Deficiency of lysosomal enzyme b-galactosidase leading to accumulation of glucosylceramides * infiltration of bone marrow, hepatosplenomegaly, skeletal and CNS complications * Autosomal recessive disorder (approx. 1 in 20,000) in general population, much higher prevalence in _\_\_\_\_\_\_\_\_\_\_\_\__ * 3 clinical subtypes * type 1 -adult, non-neuropathic form (\>95%) * type 2 -infantile, acute neuropathic form * type 3 –juvenile form * Successfully treated with _\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\__ (Ceredase)

_Gaucgers Disease_: * Failure of Glycosphingolipid breakdown * Deficiency of lysosomal enzyme b-galactosidase leading to accumulation of glucosylceramides * infiltration of bone marrow, hepatosplenomegaly, skeletal and CNS complications * Autosomal recessive disorder (approx. 1 in 20,000) in general population, much higher prevalence in _Ashkenazi Jews_ * 3 clinical subtypes * type 1 -adult, non-neuropathic form (\>95%) * type 2 -infantile, acute neuropathic form * type 3 –juvenile form * Successfully treated with _enzyme replacement therapy_ (Ceredase)