Sphingolipids, Steroids, Vitamins & Eicosanoids – Review

Question-and-answer flashcards covering sphingolipids, associated diseases, steroids, fat-soluble vitamins, eicosanoid synthesis, and pharmacological inhibitors.

What are the three major categories of sphingolipids?

Ceramides, sphingomyelins, and glycosphingolipids.

Which two components form a ceramide molecule?

A sphingosine backbone linked by an amide bond to a fatty-acid (N-acyl) chain.

Which sphingolipid is considered the simplest?

Ceramide.

What key protective role do ceramides play in the skin?

They create a barrier that limits water loss and shields against environmental damage and microbes.

What head group is attached to the 1-hydroxyl of ceramide in sphingomyelin?

Phosphocholine or phosphoethanolamine.

How are glycosphingolipids structurally defined?

Ceramides with one or more sugar residues joined by a β-glycosidic bond at C-1.

Name two subclasses of glycosphingolipids.

Cerebrosides and gangliosides.

List three sphingolipid-derived second messengers.

Sphingosine, sphingosine-1-phosphate, and ceramide.

In which membrane structure is sphingomyelin abundant and what is its function there?

Myelin sheaths of nerves; it insulates axons to speed impulse conduction.

What immune function is directed by sphingosine-1-phosphate gradients?

Egress (exit) of lymphocytes from lymphoid organs into the circulation.

Give four causes of abnormal lipid accumulation in cells.

Genetic enzyme defects, oxidative stress/inflammation, dietary or metabolic disorders (e.g., diabetes, obesity), and neurodegenerative diseases such as Parkinson’s or Alzheimer’s.

Which enzyme deficiency causes Tay-Sachs disease?

Hexosaminidase A deficiency.

Which lipid accumulates in Tay-Sachs disease?

GM2 ganglioside inside nerve cells.

What is the inheritance pattern of Fabry disease?

X-linked.

Which enzyme is deficient in Fabry disease?

α-Galactosidase A.

Which lipid accumulates in Fabry disease?

Globotriaosylceramide (Gb3).

Which enzyme deficiency causes Farber disease?

Ceramidase deficiency.

Name two clinical features of Farber disease.

Painful/swollen joints and progressive neurological decline (often with hoarseness).

Which enzyme deficiency leads to Gaucher disease?

Glucocerebrosidase deficiency.

Which two organs are typically enlarged in Gaucher disease?

Spleen and liver (hepatosplenomegaly).

Niemann-Pick disease commonly results from deficiency of which enzyme or process?

Sphingomyelinase deficiency or defective intracellular lipid transport.

From what biochemical building blocks are steroids biosynthesised?

5-carbon isoprene (terpene) units.

Describe the characteristic carbon skeleton of steroids.

Four fused rings: three six-membered (A, B, C) and one five-membered (D).

Which sterol is present in animals but absent in plants?

Cholesterol.

Which sterol is produced by fungi such as yeast?

Ergosterol.

Give two examples of medicinally useful steroids.

Cortisone (anti-inflammatory) and norethindrone (oral contraceptive).

What is the general biological role of steroid hormones?

Potent signaling molecules that regulate gene expression.

Vitamin D is biosynthetically derived from which molecule?

Cholesterol (via 7-dehydrocholesterol).

What is the digestive function of bile acids?

They emulsify dietary fats to aid pancreatic lipase digestion.

Which four human vitamins are lipid-soluble?

Vitamins A, D, E, and K.

Why can fat-soluble vitamins reach toxic levels more easily than water-soluble ones?

They are not readily excreted and accumulate in body fat and tissues.

Which lipid-soluble vitamin is structurally a terpene?

Vitamin A (retinoids).

Which polyunsaturated fatty acid is the precursor of eicosanoids?

Arachidonic acid (20:4 Δ5,8,11,14).

What enzyme catalyzes the rate-limiting step in prostaglandin synthesis?

Cyclooxygenase (prostaglandin G/H synthase, COX).

Name the two isoenzymes of cyclooxygenase in mammals.

COX-1 (constitutive) and COX-2 (inducible).

What is the main physiological role of COX-1?

Generation of prostaglandins for normal functions (e.g., gastric protection, renal blood flow, platelet TXA2).

What induces expression of COX-2?

Inflammatory stimuli such as cytokines and growth factors.

What two catalytic activities reside in each COX enzyme?

Cyclooxygenase (oxygen insertion) and peroxidase (hydroperoxide reduction).

Which intermediate is common to prostaglandins and thromboxanes?

Prostaglandin H2 (PGH2).

Which prostaglandin produced by vascular endothelium inhibits platelet aggregation?

Prostacyclin (PGI2).

Which prostaglandin causes vasodilation and decreases blood pressure?

PGE2.

Which leukotriene is a powerful chemotactic agent for neutrophils?

LTB4.

Which three leukotrienes form the slow-reacting substance of anaphylaxis (SRS-A)?

LTC4, LTD4, and LTE4.

Which enzyme do anti-inflammatory glucocorticoids inhibit to block leukotriene synthesis?

Phospholipase A2 (PLA2).

Name the 5-lipoxygenase inhibitor used for asthma management.

Zileuton.

How do NSAIDs such as aspirin relieve pain, fever, and inflammation?

By inhibiting COX activity, preventing PGH2 formation and thus prostaglandin/thromboxane synthesis.

What specific chemical reaction does aspirin perform on cyclooxygenase?

Covalent acetylation of a serine residue in the COX active site.

Why is aspirin’s inhibition of COX considered irreversible?

The acetylated serine permanently blocks substrate access; enzyme activity returns only when new COX protein is synthesized.

Which serine residue of COX-1 is acetylated by aspirin?

Serine 529 (Ser-529).

How do ibuprofen and most other non-aspirin NSAIDs inhibit COX?

They reversibly occupy the hydrophobic channel that admits arachidonic acid to the active site.