Mindmap
Cholesterol homeostasis
Inhalt der Mindmap
Cholesterol homeostasis
Generalities
- Cholesterol
- It is made up of
- A cyclopentane
- Linked to a perhydrophenanthrene
- It is made up of
- 27 C and 4 rings (A, B, C and D)
- Union of
- OH Group - C3 (gives it polarity)
- Methyl C10 and C13
- Double bond C5 - C6
- Branched hydrocarbon chain from 8C to C17
- Double bond C5 - C6
- Methyl C10 and C13
- OH Group - C3 (gives it polarity)
- Union of
- 27 C and 4 rings (A, B, C and D)
- It is made up of
- Linked to a perhydrophenanthrene
- A cyclopentane
- It is made up of
- To be able to transport
- Esterified cholesterol
- Lipoproteins are required
- Esterified cholesterol
- Insulin
- Stimulating hormone
- Cholesterol synthesis
- Hyperglycemia
- Hence
- Compensatory hyperinsulinemia
- Provides acetyl CoA
- And
- Stimulates HMG CoA reductase
- By activating protein phosphatase
- Also
- Stimulates FA synthesis
- Also
- By activating protein phosphatase
- Stimulates HMG CoA reductase
- And
- Provides acetyl CoA
- Compensatory hyperinsulinemia
- Hence
- Hyperglycemia
- Cholesterol synthesis
- Stimulating hormone
- Cholesterol
Important role in
- Fundamental molecule
- To form
- Many structures in the body
- Human breast milk
- High amounts of cholesterol
- Human breast milk
- Many structures in the body
- To form
- Form or manufacture cell membranes
- Rigid part of the cell
- Where receptors are found
- How it will be constituted
- And
- What receptors are constituted in
- And
- Its flexibility: sensitivity
- It will depend on quantity
- And
- Quality of cholesterol
- And
- It will depend on quantity
- Its flexibility: sensitivity
- And
- What receptors are constituted in
- And
- How it will be constituted
- Where receptors are found
- Rigid part of the cell
- Crucial for
- Correct development and functioning of the NS
- Allows to synthesize myelin sheaths
- Have synaptic conduction
- That neurons generate contact with each other
- Promotes neuroplasticity
- Neurogenesis
- Develop cognitive functions
- Advanced emotional
- Memory
- Rasocinium capacity
- Memory
- Advanced emotional
- Develop cognitive functions
- Neurogenesis
- Promotes neuroplasticity
- That neurons generate contact with each other
- Have synaptic conduction
- Allows to synthesize myelin sheaths
- Correct development and functioning of the NS
- Very important
- Formation of steroid hormones
- Testostenora
- Estradiol
- Estriol
- Estrone
- Progesterone
- Estrone
- Estriol
- Estradiol
- Testostenora
- Formation of steroid hormones
- Formation of bile salts
- Absorption of lipids
- And
- Secretion of cholesterol
- And
- Absorption of lipids
- Have adequate concentrations
- Of vitamin D
- Previtamin D can be synthesized
- Fat-soluble vitamin important for
- Immunological activities
- Endocrine
- Neuronal
- Sexual activity
- Cognitive function
- Due to
- Desmosterol intermediate
- Precursor of Vit D
- Desmosterol intermediate
- Due to
- Cognitive function
- Sexual activity
- Neuronal
- Endocrine
- Immunological activities
- Fat-soluble vitamin important for
- Previtamin D can be synthesized
- Of vitamin D
- Storage
- It is stored for non-energy purposes
- In adipose tissue
- Or
- Wall of blood vessels (not healthy)
- These reserves are required
- To cover
- Physiological needs
- To cover
- These reserves are required
- Wall of blood vessels (not healthy)
- Or
- In adipose tissue
- It is stored for non-energy purposes
- Fundamental molecule
Cholesterol sources
- 2 sources
- Exogenous source
- Diet
- Cholesteryl esters
- Normally provides 300 mg daily
- Endogenous synthesis
- 200-600 mg daily
- It can reach 1 g or a little more
- The more cholesterol the diet contributes
- The lower the endogenous synthesis will be
- The more cholesterol the diet contributes
- It can reach 1 g or a little more
- 200-600 mg daily
- Endogenous synthesis
- Normally provides 300 mg daily
- Cholesteryl esters
- Diet
- Exogenous source
- 2 sources
Main tissues that produce cholesterol
- Main
- Liver
- Sends cholesterol
- Throughout the body
- Intestine
- Adrenal cortex
- Gonads
- Ovaries and testes
- Gonads
- Adrenal cortex
- Cholesterol synthesis
- Produced in other tissues
- Not for general body use
- But from the same organ or tissue that produces it
- However
- Still send cholesterol to them
- However
- But from the same organ or tissue that produces it
- Not for general body use
- Produced in other tissues
- Sends cholesterol
- Liver
- Main
Location
- Enzymes for cholesterol synthesis
- In cytoplasm and endoplasmic reticulum
- Substrates
- ATP
- NAPDH + H
- Acetyl-CoA
- Origin
- FA oxidation or b-oxidation
- Oxidation of ketogenic aa
- Pure
- Leucine and lysine
- Keto and glycogens
- Threonine, isoleucine, phenylalanine, tyrosine, tryptophan
- Pure
- Pyruvate dehydrogenase reaction
- From acetate
- Use the citrate shuttle
- To get it out of the mitochondria
- To the cytosol
- To get it out of the mitochondria
- Origin
- Acetyl-CoA
- NAPDH + H
- ATP
- Enzymes for cholesterol synthesis
Treatments to lower blood cholesterol
- Diet or nutritional treatments
- Increase intake of polyunsaturated FA
- Like Omega 3, 6 and 9
- Increase intake of polyunsaturated FA
- Pharmacological level
- Statins
- Action
- Inhibit HMG CoA reductase
- However
- May also decrease
- Endogenous synthesis of coenzyme Q
- Enzyme required
- For electron transport chain
- Enzyme required
- Endogenous synthesis of coenzyme Q
- May also decrease
- However
- Inhibit HMG CoA reductase
- Action
- Statins
- Diet or nutritional treatments
Normal values or reference values
- HDL - Cholesterol
- LDL - cholesterol
- VLDL - cholesterol
- Total cholesterol
- TG
- Total cholesterol
- VLDL - cholesterol
- LDL - cholesterol
- Optimal values
- 40 - 60 mg / dL
- Less than 100 mg / dL
- 2 - 30 mg / dL
- Less than 200 mg / dL
- Less than 150 mg / dL
- Less than 200 mg / dL
- 2 - 30 mg / dL
- Less than 100 mg / dL
- 40 - 60 mg / dL
- HDL - Cholesterol
Cholesterol synthesis - Cholesterogenesis
- 5 steps
- Synthesis of mevalonate from acetatyl CoA
- 2 acetyl-CoA
- They condense to form
- The enzyme thiolase acts
- Acetoacetyl-CoA (also b-oxidation intermediate)
- Reacts with an Acetyl-CoA
- Mediated by the enzyme hydroxymethylglutaryl-CoA synthetase
- Forms 3 hydroxy 3 methyl glutaryl CoA
- It is reduced by hydroxymethylglutaryl-CoA reductase
- Forming mevalonate (alcohol of 6 carbon atoms)
- It is at this point in the process
- Where cholesterol synthesis is regulated
- When you already have
- Sufficient cholesterol
- Either from
- Endogenous synthesis or exogenous source
- It is blocked
- By negative allosteric regulation
- It is slowed or inhibited
- Mevalonate synthesis
- In addition
- Statins
- They also act on this enzyme
- Also inhibiting the synthesis of cholesterol
- They also act on this enzyme
- Statins
- In addition
- Mevalonate synthesis
- It is slowed or inhibited
- By negative allosteric regulation
- It is blocked
- Endogenous synthesis or exogenous source
- Either from
- Sufficient cholesterol
- When you already have
- Where cholesterol synthesis is regulated
- It is reduced by hydroxymethylglutaryl-CoA reductase
- Forms 3 hydroxy 3 methyl glutaryl CoA
- Mediated by the enzyme hydroxymethylglutaryl-CoA synthetase
- Reacts with an Acetyl-CoA
- Acetoacetyl-CoA (also b-oxidation intermediate)
- The enzyme thiolase acts
- They condense to form
- 2 acetyl-CoA
- Conversion of mevalonate to activated isoprenes
- Mevalonate
- It is phosphorylated
- By mevalonate kinase (phosphorylated)
- Converting it to
- Mevalonate 5 phosphate
- By action of phosphomevalonate kinase
- Mevalonate 5 diphosphate is obtained
- Then, by action of diphosphomevalonate kinase
- It becomes
- Mevalonate 3- phospho-5-diphosphate
- Which, through the action of
- Diphosphomevalonate decarboxylase
- Converts to isoprenyl diphosphate
- And this, through the action of isopentenyl diphosphate isomerase
- Becomes 3,3-dimethylallyl diphosphate
- And this, through the action of isopentenyl diphosphate isomerase
- Converts to isoprenyl diphosphate
- Diphosphomevalonate decarboxylase
- Which, through the action of
- Mevalonate 3- phospho-5-diphosphate
- It becomes
- Then, by action of diphosphomevalonate kinase
- Mevalonate 5 diphosphate is obtained
- By action of phosphomevalonate kinase
- Mevalonate 5 phosphate
- Converting it to
- By mevalonate kinase (phosphorylated)
- It is phosphorylated
- Mevalonate
- Condensation of 6 activated isoprene units to form squalene
- 3,3 Dimethylallyl diphosphate
- Binds to
- Isoprenyl diphosphate
- By action of the enzyme cis-prenyl transferase
- Giving rise to
- Geranyl diphosphate
- Which, by action of the enzyme
- Cis-prenyl transferase
- Another isoprenoid is added
- Forming farnesyl diphosphate
- And
- Two farnesyl diphosphate condense
- By action of squalene synthetase
- Giving rise to squalene
- By action of squalene synthetase
- Two farnesyl diphosphate condense
- And
- Forming farnesyl diphosphate
- Another isoprenoid is added
- Cis-prenyl transferase
- Which, by action of the enzyme
- Geranyl diphosphate
- Giving rise to
- By action of the enzyme cis-prenyl transferase
- Isoprenyl diphosphate
- Binds to
- 3,3 Dimethylallyl diphosphate
- Squalene cyclization and cholesterol formation from lanosterol
- Squalene
- Becomes lanosterol
- Which, becomes
- 14 desmethyl lanosterol
- Who becomes zimosterol
- By action of an isomerase
- Becomes cholestadienol
- Who becomes Desmosterol
- And
- By action of a reductase
- It finally turns into cholesterol
- By action of a reductase
- And
- Who becomes Desmosterol
- Becomes cholestadienol
- By action of an isomerase
- Who becomes zimosterol
- 14 desmethyl lanosterol
- Which, becomes
- Becomes lanosterol
- Squalene
Regulation of cholesterol biosynthetic pathway
- HMG CoA reductase
- Dephosphorylated is active
- When it is phosphorylated
- It is inactivated
- It is phosphorylation is catalyzed by
- AMP kinase enzyme
- Whose levels are high
- When energy levels are low
- That is, when
- ATP is degraded to AMP
- Then kinase is activated
- To inhibit cholesterol synthesis
- On the other hand
- A protein phosphatase
- Dephosphorylates HMG CoA reductase
- Keeping it active
- Dephosphorylates HMG CoA reductase
- A protein phosphatase
- On the other hand
- To inhibit cholesterol synthesis
- Then kinase is activated
- ATP is degraded to AMP
- That is, when
- When energy levels are low
- Whose levels are high
- AMP kinase enzyme
- It is phosphorylation is catalyzed by
- It is inactivated
- When it is phosphorylated
- Dephosphorylated is active
- HMG CoA reductase
Cholesterol transport
- Chemylomicrons
- Enter the liver
- Through LRP1
- Thus the exogenous cholesterol reaches the liver
- Then the exogenous and endogenous cholesterol
- Are exported by VLDL
- They pass into the bloodstream
- Endothelial lipoportein lipase
- Removes FA and some (little) cholesterol
- Thus VLDL becomes IDL
- In which it begins to predominate
- Cholesterol content on FA
- Endothelial lipoprotein lipase continues to act
- And
- IDL becomes LDL
- Greater composition: cholesterol
- Tissues have LDL receptors
- This is how cholesterol is delivered
- To other tissues
- And
- When LDL reaches its receptor in the liver
- It lets you know
- If cholesterol synthesis is required or not
- It lets you know
- When LDL reaches its receptor in the liver
- And
- To other tissues
- This is how cholesterol is delivered
- Tissues have LDL receptors
- Greater composition: cholesterol
- IDL becomes LDL
- And
- Endothelial lipoprotein lipase continues to act
- Cholesterol content on FA
- In which it begins to predominate
- Thus VLDL becomes IDL
- Removes FA and some (little) cholesterol
- Endothelial lipoportein lipase
- They pass into the bloodstream
- Are exported by VLDL
- Then the exogenous and endogenous cholesterol
- Thus the exogenous cholesterol reaches the liver
- Through LRP1
- Enter the liver
- When the liver detects
- Need for cholesterol
- Sends HDL to look for
- Cholesterol stored
- In peripheral tissues
- Which by endocrine stimulation
- Transfer cholesterol to HDL
- ABCG1 allows cholesterol output
- And
- LCAT: enzyme that incorporates it into HDL
- Thus, HDL travels to the liver
- By HDL receptors
- They deliver cholesterol
- By HDL receptors
- Thus, HDL travels to the liver
- LCAT: enzyme that incorporates it into HDL
- And
- ABCG1 allows cholesterol output
- Transfer cholesterol to HDL
- Which by endocrine stimulation
- In peripheral tissues
- Cholesterol stored
- Sends HDL to look for
- Need for cholesterol
- Chemylomicrons
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Informationen
- Beschreibung
- Mindmap am Cholesterol homeostasis, erstellt von Liz Jhorimar Herrera Moron am 01/11/2020.
- Erstellt von
- Liz Jhorimar Herrera Moron
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