Cholesterol, Lipoprotein Metabolism and Steroids Flashcards by Christine Carrera

____; organic compond with four fused rings arranged in a specific configuration (ABCD ring system)

steroids

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____: subgroup of steroids with a hydroxyl group at the 3-position of the A-ring

Sterols

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_____ is a highly hydrophobic compound, the major sterol in animal tissues

Cholesterol

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Cholesterol is an essential ______ component of all animal cell membranes (~30%)

structural

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Cholesterol is required to main both membrane structural ____ and ______ at different temperatures

integrity and fluidity

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Cholesterol enables animal cells to dispense within the cell shape in order to ____ and ______

protect membrane integrity and cell viability

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Cholesterol is a component of lipid rafts formation to facilitate _______

cell signaling

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Cholesterol is the precursor for the synthesis of:
1)
2)
3)

1) Bile Salts
2) Steroid hormones
3) Vitamin D

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____ cholesterol: found in membranes of all animal cell membranes

Free (unesterified)

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________ cholesterol:

Not found in membranes
Most of the plasma cholesterol is in this form

Esterified cholesterol (cholesteryl esters)

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Most cells have the ability to ________ ________

synthesize cholesterol

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_____, _______, and _________ (adrenal cortex, testes, ovaries) contribute most significantly to the overall cholesterol pool

Liver, Intestine, Steroidogenic Tissues

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_____ is the central organ that controls the overall cholesterol homeostasis (synthesis, distribution, elimination)

Liver

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Name the sources of liver cholesterol:
1)
2)
3)

1) De Novo Synthesis
2) Diet (delivered from chylomicron remnants)
3) Delivered via HDLs (reverse cholesterol transport)

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What is the route for cholesterol clearance from the liver?

Secretion into VLDL/LDL

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In humans, _____ b/w cholesterol influx and efflux is not precise

the balance

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The imbalance of cholesterol leads to a _______ of cholesterol in the tissues

gradual deposition

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The gradual deposition of cholesterol particularly occurs in the __________

endothelial linings of blood vessels

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Lipid depositions over time can lead to ______, causing the narrowing of blood vessels (atherosclerosis)

plaque formation

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_______ leads to an increased risk of carido-, cerebro-, and peripheral vascular disease.
(making it potentially life threatening)

Plaque Formation/Atherosclerosis

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Name the substrates for cholesterol synthesis: (3)

Acetyl CoA
Reducing equivalents NADPH
ATP is needed

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When will synthesis occur? (2)

In well fed state (when all substrates are available)

- When cholesterol supply is low

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____ of cholesterol is composed of multiple steps and broken up into 6 stages

Synthesis

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List the Stages of the Synthesis of Cholesterol in Hepatocytes

1) Conversion of acetyl CoA to HMG CoA
2) Synthesis of mevalonate
3) Conversion of mevalonate to isoprenyl pyrophosphates w/loss of CO2
4) Conversion of isoprenyl pyrophosphates to squalene
5) Conversion of squalene to lanosterol
6) Conversion of lanosterol to cholesterol

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What is the enzyme responsible for Stage 1) the Conversion of Acetyl CoA to HMG CoA?

HMG-CoA Synthase

Name the two isoenzymes (in the liver) for HMG-CoA Synthase

1) Cytosolic --for cholesterol synthesis | 2) Mitochondrial--for ketone bodies

What is the enzyme responsible for Stage 2) Synthesis of Mevalonate?

HMG-CoA Reductase

What Step in the Synthesis of Cholesterol in Hepatocytes in Rate Limiting/Key Regulatory Step?

Stage 2) Synthesis of Mevalonate catalyzed by HMG-CoA reductase

The enzyme HMG-CoA reductase is inhibited by?

Statin Drugs

_____ is an integral membrane protein of the ER facing the cytosol

Mevalonate

____ molecules of mevalonate are required to make 1 molecule of cholesterol

Each molecule of mevalonate requires _____ molecules of acetyl CoA

Ultimately, _____ molecules of acetyl CoA are required to make 1 molecule of cholesterol

Many steps of the Synthesis of Cholesterol are _______

IRREVERSIBLE | humans lack enzymes to perform reverse reactions

Cholesterol ______ be metabolized to CO2 like sugars and fats

can NOT

Since the synthesis of cholesterol takes place in the ______, many intermediates are charged to make them soluble

cytoplasm

The intermediates of cholesterol are charged to make them soluble in the cytoplasm, until the formation of ______

squalene

At the point of Squalene formation, the molecule is associated with ________

carrier proteins

Regulation of Cholesterol Synthesis via HMG CoA Reductase: Hormone Regulation: _____ and _____ UPREGULATE HMG CoA Reductase expressions

Insulin and Thyroxine

Regulation of Cholesterol Synthesis via HMG CoA Reductase: Hormone Regulation: _____ and _____ DOWNREGULATE HMG CoA Reductase expressions

Glucagon and Glucocorticoids

Sterol-independent covalent modifications--> ________/_________ occurs via AMPK reflecting the energy state of the cell

phosphorylation/dephosphorylation

Describe the Sterol-DEPENDENT regulation-- 1) 2)

enzyme gene transcription and expression via SREBP transcription factor enzyme degradation via ubiquitination

The intact sterol nucleus is eliminated by: 1) 2)

1) conversion to bile acids and bile salts (that are excreted in feces (2-3%) 2) secretion of cholesterol into the bile (transported to intestion for elimination as fecal cholesterol)

Some of the cholesterol in the intestine is modified by ____ before excretion

bacteria

____ is a watery mix (greenish-yellow) or organic and inorganic compounds produced by liver to facilitate digestion of lipids in small intestine

Bile

______ is the major constituent of bile produced in liver cells from bile acids

Bile Salts

____ are the precursor for the synthesis of bile salts, produced in liver cells from cholesterol

Bile Acids

Cholesterol --> ______ ---> _______

Cholesterol --> Bile Acids --> Bile Salts

_____ undergo a circulation where they are reabsorbed from the intestine and sent back to the liver to be used again

Bile salts

Very small loss (

steroid nucleus

_______ (gall stones) form in the gall bladder where bile is stored

Cholelithiasis

Origin of gall stones: dervied from cholesterol and result from ____________ and/or ________ in the gall bladder (the bile salts are required to solubilize free cholesterol)

too little bile salts | too much cholesterol

Name the possible causes of gall stones: (3)

1) inefficient enterohepatic cycling 2) liver dysfunction 3) other idiopathic reason

______: spherical macromolecular complexes of lipids and specific proteins (apolipoproteins)

Lipoproteins

Function of LIpoproteins

To transport cholesterol, fats and fat-soluble compounds in the plasma

Types of Lipoproteins: (4)

Chylomicrons, VLDL, LDL, HDL

____ transport of dietary lipid, produced in enterocytes

chylomicrons

_____ - transport of newly synthesized lipids produced in hepatocytes

VLDL

______ - transport of cholesterol to the peripheral tissues

LDL

_______ - transport of cholesterol from the periphery to the liver

HDL

Core of Lipoproteins:

Neutral Lipids (TAG) and cholesteryl esters (hydrophobic)

Lipoproteins have a ______- composed of phospholipid (PC and SM) and free cholesterol (hydrophilic)

polar lipid surface

_________ _________: 11 different types of Apo proteins found in human (Apo A, ApoB, ApoC, ApoD, Apo(a)) specific for each class

Amphipathic Apolipoproteins

______: - size varies on meal content - largest in size - least dense - contain highest percentage of fat - produced by gut cells

Chylomicrons

_____: - similar to chylomicrons - produced by hepatocytes - smaller and more dense - contain high % of fat

VLDLs

_______: - highest % of cholesterol - produced from VLDL via lipolysis in blood - carry the "bad" cholesterol

LDL

_____: - contain highest % of protein - contain 2nd highest % of cholesterol - carry the "good" cholesterol

HDL

The ____ and ____ of lipoproteins are routinely used in plasma lipid profiling as part of the separation process

size and density

Metabolism of Chylomicrons: 1). Chylomicrons are formed in the ER and Golgi of intestinal mucosal cells, using _____ as scaffold protein

Apo B-48

Metabolism of Chylomicrons: 2). Lipids (TAG, cholesterol, PL) are transferred to ApoB-48 via _________________

Microsomal Transfer Protein (MTP)

Metabolism of Chylomicrons: 3) "Nascent" chylomicrons containing DIETARY LIPIDS as well as FAT-SOLUBLE compounds (vitamins A, D, E, K) are excreted through ____________

plasma membrane into the lymph

Metabolism of Chylomicrons: 4) From the lymph, they enter blood stream where chylomicrons undergo _______________ from HDL (ApoC and ApoE)

modifications and require additional Apo-Es

Metabolism of Chylomicrons: 5) Peripheral cells expressing lipoprotein lipase (LPL) hydrolyze TAGS to _________.

FA and glycerol

Metabolism of Chylomicrons: 6). The remaining is cleared from the blood stream by the ______ via ______

liver via endocytosis

Which of the lipoproteins would you expect to vary based on recent meals?

Chylomicrons and VLDL

Metabolism of VLDLs: 1) VLDLs are assembled in the ____ and ____ of liver cells - full length Apo B-100 is used as scaffolding protein

ER and Golgi

Metabolism of VLDLs: 2) VLDL are directly secreted into the blood stream, where they acquire ____ and ____ from HDLs

Apo C-II and Apo-E

Metabolism of VLDLs: 3) ____ (activated by Apo C-ll) hydrolyzes VLDLs TAGs and release FA to the peripheral tissues

LPL

Metabolism of VLDLs: 4) VLDL ______ in size and become ______ becoming VLDL "remnant" or IDL

decrease in size and become denser

Metabolism of VLDLs: 5) Additional modifications transfer of cholesteryl esters from HDL to these particles transforming _____ into ____

VLDL into LDLs

Metabolism of VLDLs: 6) _____ remaining in the LDL is a ligand recognized by the LDL Receptors (LDLR) - taken up via endocytosis

Apo B-100

LDL-released cholesterol is immediately used for | ______, _____ or ________

membrane assembly, steroid hormones or bile acid synthesis

If cholesterol is not immediately used, 1) 2)

1) converted to CE by ACAT and stored | 2) serves as major regulator of cholesterol homeostasis

Oversupply of cholesterol will: 1) 2) 3)

1) Inhibit de novo synthesis of cholesterol 2) Inhibit expression of LDLR 3) Activate ACAT to produce CE

Name the factors that increase modified LDL in circulation 1) 2) 3)

1) High Blood Sugar 2) Oxidative stress caused by (infection, smoking, drugs,e tc) 3) Chemicals present in tobacco smoke

____ and _____ will have an increased risk of cardiovascular disease

smokers and diabetics

It is thought that Vitamins A, E, C and other antioxidants can have a _______ effect

protective

________: the efflux of cholesterol from peripheral tissues to HDL

Reverse Cholesterol Transport

___(1)__ are considered "good" cholesterol. Elevated __(1)__ compared to __(2)___ are considered "good", however the ratio of LDLs to HDLs is usually considered.

1) HDLs, 2) LDLs

HDL's _____ is produced within the liver and intestinal cells secreted in the circulation as free apolipoprotein

Apo A-1

HDL;s serve as a reservoir of ______ and _____ for transfer to other lipoproteins

Apo CII and Apo E

Lipoprotein Metabolism: Diseases _____________: (familial hyperchylomicroenmia) - deficiency of Apo Cll or lipoprotein lipase (LPL) - rare, autosomal recessive

Type l hyperlipoproteinemia

Lipoprotein Metabolism: Diseases _____________: (familial hypercholesterolemia) - defect in LDL RECEPTOR - Autosomal dominant (1 in 500) VERY COMMON

Type lla hyperlipidemia

What are the two types of steroid hormones?

Corticosteroids and Sex Hormones

_____ is typically used in anti-inflammatory drugs

Cortisol (Corticosteroids)

_______ - control menstrual cycle - promote development of female secondary sex characteristics

estrogens

________ - secretory phase of uterus and mammary glands - implantation and maturation of fertilized ovum

Progesterone

___________ - stimulates spermatogenesis - promotes development of male secondary sex characteristics - Promotes anabolism - Masculinization of the fetus

Testosterone

Synthesis and secretions (of steroid hormones) occur in the: ______, _______ and ______

adrenal cortex, ovaries and placenta, and the testes

What steroid hormones are produced by the adrenal cortex?

Cortisol, Aldosterone, Androgens

What steroid hormones are produced by the ovaries and placenta?

Estrogens and Progestins

Steroid Hormones are transported by the _____ from their sites of synthesis to their target organs

blood

Because of the hydrophobicity of the steroid hormones, they must be complexed with a plasma protein, _____

albumin

Cholesterol, Lipoprotein Metabolism and Steroids Flashcards

(103 cards)