BIOCHEM 2: Metabolism of Sphingolipids and Other Lipids

sphingolipids

these are membrane lipids found in the membranes of nerve cells

true

True or False: Structurally, sphingolipids are the amide derivative of the amino alcohol called sphingosine

1. ceramides

2. sphingomyelins

3. cerebrosides

4. gangliosides

What are the 4 groups sphingolipids can be classified into?

ceramides

these consist of a fatty acid covalently linked to a sphingosine molecule through an amide bond.

sphingomyelins

these are ceramides with a phosphocholine group linked to the sphingosine’s OH group.

cerebrosides

these are ceramides that have only one sugar unit linked to the sphingosine’s OH group.

gangliosides

these are ceramides that have MORE than one sugar unit linked to the sphingosine’s OH

ceramides

What is the precursor to all other sphingolipids?

true

True or False: Cells make ceramides by condensing together an activated molecule of palmitic acid (i.e. palmitoyl CoA) and a molecule of the amino acid serine

condensation

The first rxn in the biosynthesis is a _____________ rxn where palmitoyl CoA and serine to give 3-ketosphinganine

synthase

What is the enzyme that catalyzes this condensation rxn?

reduced

In the second reaction in the biosynthesis, 3-ketosphinganine is _______ by addition of hydrogen to the carbonyl group to obtain sphinganine.

NADPH

What is the cofactor that is required in order to have hydrogens to reduce something?

true

True or False: In the third reaction of biosynthesis of sphingo, a FA is added to the amino group of sphinganine to give the dihydroceramide.

lysosomes

This is where sphingolipids are broken down into

these are structures in the cytoplasm that contain a large number of digestive enzymes that break down any biomolecule (lipid, protein, or carbohydrate)

1. FA

2. sphingosine

These are the final end products of sphingolipid degradation, THESE ARE SAFE PRODUCTS

cytotoxic

The intermediates in the degradation of sphingolipids are ________ and their accumulation in neurons lead to cell death.

true

True or False: In sphingolipid degradation, Mutations that render any of the degradative enzymes dysfunctional lead to accumulation of cytotoxic intermediates that kill neurons.

Tay-Sachs disease

this is a disease that results from a deficiency in the enzyme HEX A

deficiency in HEX A enzyme cause the accumulation of the cytotoxic ganglioside GM2

50%

About _____% of the cholesterol in the body is used to make bile acids in the liver.

10%

About ____% of the cholesterol is used to make steroid hormones by the endocrine glands.

40%

About ____% of cholesterol is used to make membranes.

consuming more plant products than animal products in our diet

Cholesterol is in animal fat, so how would one lower their cholesterol levels?

acetyl CoA

What is the precursor for cholesterol biosynthesis?

liver

Where does the biosynthesis of cholesterol mainly occur?

1. Condensation of three Acetyl CoA molecules to isoprenoid intermediates

2. Condensation of isoprene intermediates a linear hydrophobic molecule called squalene

3. Cyclization of the linear squalene to cholesterol

What 3 rxns are involved in the biosynthesis of cholesterol?

1. endogenous (cholesterol made by body)

2. exogenous (cholesterol obtained from diet, beef)

What are the 2 sources of cholesterol?

receptor mediated endocytosis

All cells in the body absorb LDL particles by ____________ to obtain the cholesterol they need.

rise

If you have a cholesterol rich meal, your LDL levels will rise or fall?

HMG CoA reductase

Cholesterol inhibits the _____________ enzyme which stops cells from making their own cholesterol.

feedback inhibition

Cholesterol inhibiting the HMG CoA reductase enzyme is an example of what?

ribosome

Cholesterol also stops the _______ from making the HMG CoA reductase enzyme to completely shut down cholesterol biosynthesis.

true

True or False: Cholesterol stopping ribosomes from making HMG CoA reductase and inhibits someone from making their own cholesterol then allows for the body to import more LDL from circulation

LDL

Sustained high levels of ______ in circulation lead to atherosclerosis and increases the heart attack/stroke risk

HDL

Cells then start to eliminate the excess cholesterol that they do not need by packaging it into ___________ particles and release that into circulation for liver to absorb it and incorporate it into bile for excretion in feces.

NO: heredity and genetics play a role

Are bad diet and poor food choices the only reason why people elevated LDL levels?

1. Drugs that inhibit the synthesis of indigenous cholesterol by inhibiting HMG CoA reductase

2. Drugs that block intestinal absorption of dietary cholesterol

What are the 2 groups of cholesterol lowering drugs?

statins

What is an example of drugs that inhibit the synthesis of indigenous cholesterol by inhibiting HMG CoA reductase?

^^^ these kinds of drugs also increase HDL levels, allowing the body to excrete more cholesterol

Ezetimibe (Zetia)

What is an example of drugs that block intestinal absorption of dietary cholesterol?

^^^ these are resin molecules that bind to cholesterol in the GIT blocking its absorption into the main circulation and let it be eliminated in feces

steroid hormones

these are synthesized from CHOLESTEROL in the endocrine glands

androgens and estrogens

these are the male and female sex hormones

progestins

these are steroid hormones that regulate events during pregnancy

glucocorticoids

this is a steroid hormone that has anti-inflammatory roles

mineralocorticoids

these are steroid hormones that regulate salt and water retention in the body

eicosanoids

these are biologically active FA that are made from arachidonic acid, and they are responsible for inflammatory response

1. prostaglandins

2. thromboxanes

3. leukotrienes

What are the 3 families that make us eicosanoids?

synthesis

An eicosanoids action is localized to their site of _______

erythrocytes

Eicosanoids are synthesized by all cells except what?

mediators of inflammation

these get released in a case of injury or infection and they bind to the cell surface receptors which activates the phospholipase A2 enzyme

cylooxygenase (COX)

this converts arachidonic acid to the prostaglandin known as PGH2

thromboxane synthase

this enzyme converts PGH2 to thromboxanes

lipoxygenase

this enzyme converts arachidonic acid to leukotrienes

1. leukotrienes

2. prostaglandins

____________ + ____________ are made from the same starting molecule (arachidonic acid) by the effect of two different enzymes.

true

True or False: Leukotrienes and prostaglandins both being made from arachidonic acid by different enzymes explains why inhibitors of COX (i.e. the NSAIDs), e.g. Aspirin, are used to treat inflammation but not asthma.

Cox 1

this is an enzyme required to maintain the integrity of the mucous lining in the stomach to protect it from the highly acidic environment required for digestion

weakens the mucous lining resulting in stomach ulcers

What happens if I inhibit COX-1?

COX-2

this is an enzyme that is responsible for prostaglandin synthesis

non-selective COX inhibitors

these inhibit both COX-1 and COX-2 and therefore causes stomach ulcers

NO

If an inhibitor is selective to COX-2 only will there be gastric side effects?

1. A

2. D

3. E

4. K

What are the 4 lipid soluble vitamins?

vitamin A synthesis

1. Retinal is the form important for vision

2. Growth and differentiation of cells.

3. Reproduction (spermatogenesis, oogenesis, and embryonic growth).

4. Regulation of the immune system.

What are the biological roles of vitamin A?

blindness (retinal)

Vitamin A deficiencies can lead to ______

true

True or False: The production of vitamin D3 in humans is adequate when sufficient sunlight is available

1. Induces biosynthesis of proteins required for the absorption of Ca2+ and PO43-

2. Essential for forming and maintaining integrity of bones

What are the biological roles of vitamin D?

1. Essential for reproduction (its deficiency causes infertility in both males and females).

2. Antioxidant (protect fatty acid chains from oxidation).

3. High vitamin E intakes are correlated with a reduced risk of cardiovascular diseases.

What are the biological roles of vitamin E?

true

True or False: Deficiency in vitamin E occurs due to genetic abnormalities in the α-tocopherol transfer protein and as a result of various fat malabsorption syndromes.

required for normal blood clotting

What are the biological roles of vitamin K?

bleeding disorders

A deficiency in vitamin K can cause what?