Biochemistry Yr2: Cholesterol Derivatives | Quizlet

cholesterol is what?

cholesterol is what?

-cholesterol is main steroid in the human body.

-cholesterol is the precursor of all steroids in the body- corticosteroids, sex hormones, bile acids and vitamin D3.

- cholesterol is an amphipathic lipid, which is an essential component of membrane and of the outer layer of plasma lipoproteins (LP).

coprostanol

coprostanol is the main sterol in the faeces that is formed by the bacteria in the lower intestine.

where are primary bile acids synthesised?

the primary bile acids are synthesised in the liver.

2 types of primary bile acids

the 2 types of primary bile acids are:

1) cholic acid

2) chenodeoxycholic acid

where are secondary bile acids formed?

secondary bile acids are formed from the primary bile acids after 7 alpha- dehydroxylation by intestinal bacteria

2 types of secondary bile acids

the 2 types of secondary bile acids are:

1) deoxycholic acid (from cholic acid)

2) lithocholic acid ( from chenodeoxycholic acid).

how much bile acids are eliminated?

1g per day- eliminated cholesterol from the body.

0.5g in the faeces after conversion into bile acids

0.5 g in the faeces as cholesterol.

synthesis of bile acids- main points

1) In the liver, cholesterol is partly degraded resulting in the synthesis of the primary bile acids (cholic and chenodeoxycholic acids) which are the end products of cholesterol utilisation.
2) Synthesis of the bile acids requires 17 individual enzymes and occurs in multiple intracellular compartments that include the cytosol, endoplasmic reticulum (ER), mitochondria and peroxisomes.
3)Both bile acids derives from a common precursor- 7 alpha hydroxycholesterol.
4) the key enzyme in the synthesis is 7 alpha-hydroxylase (microsomal enzyme) requires, oxygen, NADPH and cytochrome P450 (CYP7A1) and vitamin C- typical monooxygenase.
5) Another monooxygenase 12 alpha-hydroxylase (CYP8B1) is involved in the synthesis of cholic acid.
6) Bile acids are carboxylic acids and contains 24C atoms- in the pathway3C atoms are eliminated as propionyl-CoA.

synthesis of bile acids (image)

Synthesis of conjugated bile acids

In peroxisomes, the primary bile acids are conjugated with glycine or taurine.

conjugated bile acids include glycoconjugates and tauroconjugates ( ratio 3:1).

from cholic acid- glycocholic and taurocholic acids.

from chenodeoxycholic acid- glycochenodexycholic and taurochenodeoxycholic acids.

conjugated bile acids are more amphipathic and more easily secretable and less cytotoxic.

synthesis of conjugated bile acids (image)

conjugated bile acids

bile salts

bile salts are important components of bile.

in bile salts, there are a significant amount of what?

In bile salts, there are a significant amount of sodium (Na+) and potassium (K+) and the pH is alkaline ( alot of HCO3-).

bile acids and their conjugates are in the form of salt- "bile salts".

how does hepatic bile differ from gall bladder bile?

hepatic bile differs from gall bladder bile as the latter is more concentrated, more dense, could be more alkaline and contains more bile acids, cholesterol, mucin and bile pigments than hepatic.

properties of bile

properties of bile are:

1) emulsification

2) neutralisation of acid

3) excretion

primary physiologically significant function of bile acids

their synthesis and subsequent excretion in the faeces represent the only significant mechanism for the elimination of excess cholesterol.
Bile acids and phospholipids solubilise cholesterol in the bile, thereby preventing the precipitation of cholesterol in the gallbladder.
They facilitate the digestion of dietary triacylglycerols by acting as emulsifying agents that make fats accessible to pancreatic lipases.
They facilitate the intestinal absorption of lipids and fat soluble vitamins.

bile acid function

fate of bile acids

formation of secondary bile acids

enterohepatic circulation

regulation of bile acid synthesis 1

regulation of bile acids synthesis 2

regulation of bile acids synthesis 3

cholelithiasis

cholelithiasis is a disease associated with the forming of gall stones leading to obstructive jaundice.

how is cholesterol secreted?

the secretion of cholesterol is facilitated by the secretion of bile acids and phospholipids (lecithins).

cholesterol deposits trigger what?

cholesterol deposits trigger inflammatory process by lowering the pH, decreasing of cholesterol solubility.

therapy for cholelithiasis

therapy for cholelithiasis include:

1) surgical therapy

2) systemic- derivatives of bile acids, chenodeoxycolic acid and ursodeoxycholic acid (Ursofalk).

deposition of cholesterol

if the ration between the cholesterol and those compound in gall bladder is impaired leading to deposition of cholesterol.

types of gall stones

the 2 types of gall stones are:

1) cholesterol stones

2) pigments gallstone

Cholesterol stones

cholesterol stones are the main type (70%)- Ca2+ precipitates of cholesterol.

Pigment gallstones

pigment gallstones contains Ca2+ precipitates of bilirubin, cholesterol, carbonates and phosphates.

cholesterol is the precursor of what?

cholesterol is the precursor of all 5 classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens and progestins.

where are the 5 classes of steroid hormones synthesised?

the 5 classes of steroid hormones are synthesised in the adrenal cortex, ovaries, testes and ovarian corpus luteum.

steroid hormones are transported through the blood from where?

steroid hormones are transported through the blood from their sites of synthesis to their target organs.

In blood, the steroid hormones are bound to what?

in blood, the steroid hormones are bound by plasma proteins (albumin and specific transport proteins).

because of the hydrophobicity of steroid hormones, they cross into where?

because of the hydrophobicity of steroid hormones, they cross the cell membrane and bind to specific receptors in either the cytoplasm or nucleus.

the bound receptors then bind to DNA to regulate gene transcription.

all 5 classes of steroid hormones share what?

all 5 classes of steroid hormones share the 17 carbon steroid structure (with the exception of vitamin D): cyclopentaneperhydrophenantrene cycle.

cyclopentanoperhydrophenanthrene

Common molecular nucleus of steroids

pregnanes

pregnanes contains 21 carbons

androstanes

androstanes contains 19 carbons

estranes

estranes contain 18 carbons

pregnenolone

pregnenolone is the common precursor of all steroid hormones.

the conversion of a 27 carbon cholesterol to the 18,19, 21 carbon steroid hormones involves what?

the conversion of a 27 carbon cholesterol to the 18,19,21 carbon steroid hormones involves the rate limiting, irreversible cleavage of a 6 carbon residue from cholesterol, producing pregnenolone (C21) plus isocaproaldehyde.

Pregnenolone is produced directly from what?

pregnenolone is produced directly from cholesterol, the precursor molecule for all C18, C19 and C21 steroids.

progesterone is produced directly from what?

progesterone is produced directly from pregnenolone and secreted from the corpus luteum, responsible for changes associated with luteal phase of the menstrual cycle, differentiation factor for mammary gland.

progesterone is also produced in where?

progesterone is also in testes, adrenal cortex and in placenta during pregnancy.

aldosterone

aldosterone is the principal mineralocorticoid, produced from progesterone in the zona glomerulosa of the adrenal cortex.

function of aldosterone

aldosterone raises blood pressure and fluid volume.

aldosterone increases Na+ uptake in the kidney.

cortisol

cortisol is the dominant glucocorticoid in humans, synthesised from progesterone in the zona fasciculata of the adrenal cortex.

function of cortisol

cortisol is involved in stress adaptation, glucose, lipid and protein metabolism, elevates blood pressure and Na+ uptake, numerous effects on the immune system,

testosterone

testosterone is an androgen, a male sex hormone synthesised in the testis, responsible for secondary male sex characteristics, produced from progesterone.

estradiol

estradiol is an estrogen, a principal female sex hormone, produced in the ovary, responsible for secondary female sex characteristics.

the synthesis of a particular steroid hormone class by a given cell type depends on what?

the synthesis of a particular steroid hormone class by a given cell type depends upon its peptide hormone, its receptors and its genetically expressed enzymes.

each peptide hormone is responsible for what?

each peptide hormone is responsible for stimulating the synthesis of a particular class of steroid hormones

luteinising hormone releases what?

luteinising hormone (LH) is made from progesterone and testosterone.

adrenocorticotropic hormone (ACTH) releases what?

ACTH produces cortisol.

Follicle-stimulating hormone (FSH) releases what?

FSH releases estradiol

angiotensin I/III releases what?

angiotensin I/III releases aldosterone.

steroid hormone synthesis

principal synthetic pathway of steroid hormones

the adrenal cortex is responsible for the production of what?

the adrenal cortex is responsible for production of 3 major classes of steroid hormones

3 classes of steroid hormones

the 3 classes of steroid hormones are:

1) glucocorticoids

2) mineralocorticoids

3) androgens

glucocorticoids regulate what?

glucocorticoids regulate carbohydrate metabolism

mineralocorticoids regulate what?

mineralocorticoids regulate the body levels of sodium and potassium.

androgens regulate what?

androgens whose actions are similar to that of steroids produced by the male gonads.

3 main tissues of adrenal cortex

the 3 main tissues of adrenal cortex are:

1) zona glomerulosa (aldosterone)

2) zona fasciculata (cortisol)

3) zona reticularis (androgens)

although the pathway to pregnenolone synthesis is the same in all zones of the cortex, the zones are what?

although the pathway to pregnenolone synthesis is the same in all zones of the cortex, the zones are historically and enzymatically different and produce exact steroid hormones

adrenal gland cross sections

steroids of the adrenal cortex

regulation of adrenal steroid synthesis

functions of glucocorticoids

functions of mineralocorticoids

functions of androgens

cholesterol pathways to form aldosterone, glucocorticoids etc

gonadal steroid hormones

gonadal steroid hormones in females

estrogen synthesis

vitamin D

vitamin D is a steroid hormone that functions to regulate specific gene expression following interaction with its intracellular receptor

the biologically active form of vitamin D

the biologically active form of vitamin D is 1,25 dihydroxy vitamin D3 (1,25-(OH)2 D3 also termed calcitriol.

function of calcitriol

calcitriol functions primarily to regulate calcium and phosphorus homeostasis.

active calcitriol is derived from what?

active calcitriol is derived from ergosterol (produced in plants) and from 7-dehydrocholesterol (produced in the skin).

Ergocalciferol (Vitamin D2) is formed by what?

ergocalciferol (vitamin D2) is formed by UV irradiation of ergosterol.

in the skin, 7-dehydrocholesterol is converted to what?

in the skin, 7-dehydrocholesterol is converted to cholecalciferol (vitamin D3) following UV radiation.

precursors of vitamin D

1) ergosterol

2) 7-dehydrocholesterol

3) vitamin D2

4) vitamin D3

activation of vitamin D

Synthesis of calcitriol

biological activity of calcitriol

biological activity of calcitriol 2

role of calcitriol in the intestine, bone, immune cells and tumour microenvironment.