Polar derivatives (break down particles) of cholesterol that solubilize dietary lipids - Glycocholate - Taurocholate Detergent Solubilization: - exposes more surface area of cholesterol to digestive action of lipases - increases absorption of cholesterol in intestines Localization: - synthesized in liver - Stored in gall bladder - function in small intestine

used to synthesize cholesterol and ketone bodies 2 isozymes of HMG-CoA reductase - cytoplasm-cholesterol - mitochondria-ketone bodies

Extra SHIT Flashcards by Connor Schmidt

Steroid Hormones

-synthesis of 5 hormones

Cholesterol (27C)
Pregnenolone (21C)
Progestagens (21C)**startof 5 classes of steroid hormones

Branches:INTO

Glucocorticoids (21C)
Mineralocorticoids (21C)
Androgens (19C) convert to Estrogens (18C)

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5 classes of steroid hormones

Progestagens (21C)
-synthesized in corpus luteum 
Ex: Progesterone
-prepares lining of uterus for implantation of an ovum 
-maintenance of pregnancy

Glucocorticoids (21C)
-synthesized in adrenal cortex
Ex; Cortisol
-promotes gluconeogenesis and glycogen synthesis

Mineralocorticoids (21C)
-synthesized in adrenal cortex
Ex:Aldosterone:
-act at distal tubules of kidney to increase the reabsorption of Na+ and excretion of K+ and H+
-increases blood volume and blood pressure

Androgens (19C)
Synthesized in testes
Ex: Testosterone
-developement of male secondary sex characteristics

Estronges (18C)
Ex: Estrone
-developement of female secondary sex characteristics

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Cytochrome P450 System

family of proteins containing a cytochrome with a bound heme

Localization:

1) Cellular: 2 forms:
- Mitochondrial-hydroxylation of steroid hormones
- ER-detoxification of drugs/toxins
2) Organs
- liver, small intestine, kidney, steroid hormone producing tissue

Function:
Detoxification of foreign substances
-Hydroxylation of phenobarbital and polycyclic aromatic hydrocarbons
-metabolizing drugs (caffeine, ibuprofen etc)

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Bile Salts

Polar derivatives (break down particles) of cholesterol that solubilize dietary lipids

Glycocholate
Taurocholate

**Detergent

Solubilization:

exposes more surface area of cholesterol to digestive action of lipases
increases absorption of cholesterol in intestines

Localization:

synthesized in liver
Stored in gall bladder
function in small intestine

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Cells that need cholesterol?

take up LDLs by receptor-mediated endocytosis

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Cholesterol Synthesis

Overview

27 Carbons are derived from acetyl CoA

Cellular Localization:

cytoplasm
ER

Organ Localization:

Liver parenchymal cells
intestine (secondary)

3 stages:

synthesis of IPP in cytopplasm
6 molecules of IPP condense to form squalene-ER
3) Cyclization of squalene

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10 Steps of Cholesterol

1) HMG-CoA Synthase
- Acetyl CoA + AcetoAcetyl CoA-> 3-HMG-CoA

2) HMG-CoA reductase
-commited step/regulated
-integral membarne protein of ER with catalytic domain into cytoplasm where reaction occurs
HMG-CoA->Mevalonate
-coenzyme: 2NADPH to NADP+

3,4,5) Melavonate-> IPP
Kinase, Kinase, Kinase/Decarboxylase
-6 molecules of IPP used to synthesize 1 cholesterol molecule

6) IPP-> DPP
- isomerization

7)Geranyl transferase
-catalyzes a series of transferase reactions of 5C molecules
IPP+DPP-> GPP
GPP + IPP-> FPP (15C) does this twice

8) Squalene synthase
- 2 FPP molecules combine at tail to form squalene (30C)
- NADPH to NADP+

9) Squalene Monooxygenase
- Squalene-> Squalene Epoxide
- requires moleculare oxygen
- coenzyme NADPH to NADP+

10)Oxidosqualene cyclase
Squalene epoxide-> Lanosterol
-ring closure

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HMG

used to synthesize cholesterol and ketone bodies

2 isozymes of HMG-CoA reductase

cytoplasm-cholesterol
mitochondria-ketone bodies

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Lanosterol-> Cholesterol

19 steps
conversion involves:
-reduction of carbon chain from 30 to 27
-removal of 2 methyl on C4
-removal of methyl on C4
-migartion of double bond from C8 to C5
-reduction of Double bond C25-C25

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SLOS

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

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Synthesis of Sphingomyelin

Ceramide-> Sphingmyelin

Phosphatidyl choline drops of head group phosphate+ ethanol amine +3ch3 or (CHOLINE)
DAG released

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Synthesis of Cerebroside

Ceramide + UDP glucose-> Cerebroside

-attachment of 1 Carb to serine OH

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Synthesis of Gangliosides

Ceradmide + multiple carbohydrates after cerebroside

carbs added one at a time
are activated UDP-glucose/galactose

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Phosphatidylcholine synthesis:

-2way

1) activation of choline which is then attached to head group
2) Methylation of ethanol amine by Phosphatidylethanol amine methyltransfers
- requires 3SAMS as methyl donor

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Where is Cardiolipin found?

Mitochondria

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In mammals, this is the major site of triacylglycerol synthesis

Liver

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The reduction of this metabolite supplies Glycerol 3 Phosphate for acylglycerol synthesis

Dyhydroxy 3-Phosphate

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Component of myeline sheath

Sphingomyeline

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All of the carbons in cholesterol are derived from this molecule?

Acetyl CoA

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This the process by which LDL enter the cell

receptor-mediated endocytosis

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Cholesterol and triacylglycerols are transported in the body fluids in this form

Lipoprotein particles

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Vitamin is a derivative of cholesterol

Vit D

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Primary bile salt

glycocholate

-or taurocholate

This is a derivative of cholesterol and the precursor of the steroid hormones

Pregnonenolene

In mammalian cells, phosphatidate is synthesized in?

Cytoplasmic face of smooth ER | -Outer mitochondrial membrane

Is composed of a fatty acid linked to sphingosine via an amide bond

Ceramide

In the biosynthesis of phosphatiidates, the fatty acyl group attached to the C-2 position is usually?

unsaturated | -c1 usually saturated

Is the 9 Carbon sugar that is a component of gangliosides

Sialic acid or N-acetylneuramic acid

In biosynthesis of sphingosine, the condensation of palmitoyl-CoA and serine requires the coenzyme

PLP

In membrane lipid biosynthesis, the nucleotide___ is used to activate the components in the reaction

CTP

The synthesis of ___ is the committed step in cholesterol biosynthesis

mevalonate

___ is the 30C (triterpene) precursor of cholesterol biosynthesis

Squalene

is the major carrier of cholesterol esters in the blood

LDL

Vit D3 is converted into ___ which is an active hormone that functions as a transcription factor

Calcitriol

What is the common precursor for both phosphatidyl inositol and triacylglycerol

Phosphatidylate

Phosphatidate is formed from?

Glycerol 3-Phosphate | 2 Fattty acyl CoA

In phosphatidate inositol, what usually occupies C1 and C2

C1=stearic acid | C2=arachidonic acid

The highest concentration of sphingolipids is found in the?

CNS

The starting materials necessary to synthesize sphingosines?

Palmitoyl CoA and Serine=Ceramide

What is the major component of LDLs?

Cholesterol Linoleate

Respiratory distress syndrome is caused by?

a failure in the biosynthetic pathway of dipalmitoyl phosphatidyl choline

Tay Sachs is caused by

an inability to degrade gangliosides

HMG Coa is synthesized from?

Acetyl CoA and AcetoAcetyl CoA

Feedback regulation of cholesterol synthesis is mainly controlled at the step catalyzed by the enzyme?

3-hydroxy-3-methylglutary CoA reductase

The role of lipoprotein particles are to:

Solubilize hydrophobic lipids | Contain cell-targeting signals

The major carrier of dietary fat from the intestine is

chylomicrons

The LDL receptors on the plasma membarne are localized in

coated pits that contain the receptors of clathirin coated proteins

What combines to form major bile salt

Cholic acid and Glycine

Hydroxylation of cholesterol by cytochrome P450 requires:

NADPH | activated O2

What are the causes and symptoms of Familial hypercholesterolemia

Hallmark-Genetic disease is elevated cholesterol levels in serum - cholesterol deposits in blood vessels and cause heart attacks, even in young children - caused by a deficiency in the LDL receptor

What is the role of CTP in the synthesis of Phospholipids

In de novo synthesis - CTP is used to activate Phosphatidate to form CDP-diacylglycerol and pyrophosphate - pyrophosphate is hydrolyzed and drives reaction - Activated DAG can then react with another alcohol, such as inositol and CMP is released

What are the 3 steps of cholesterol synthesis

1> synthesis of isoprene units (IPP) 2) condensation of 6 units to form squalene 3) cyclization of squalene

What is the role of phosphatidyl choline in the synthesis of sphingomyelin

Phosphatidyl choline provides the polar head form sphingomyelin -phosphocholine group is transferred to ceramide from phosphatidyl choline to form sphingomyelin and DAG

List the types of lipoproteins and give primary physiological role of the lipoprotein

``` Chylomicrons-transport dietary fat VLDL-transport endogenous fat IDL-precursor to LDL LDL-transport cholesterol HDL-reverse transport of cholesterol form tissue to liver ```

How do blood levels of lipoproteins serve diagnostic purposes?

The ratio of LDL to HDL is important -to much LDL (bad cholesterol) can be dangerous because increased resistance for plaque formation and heart disease. HDL serves in a protective capacity, shuttling cholesterol forms eh cells back to liver to maintain proper levels LDL/HDL ratio should be 3.5 in humans