Biochemistry Flashcards: Lipids, Lysosomal Storage Diseases, Ketone Bodies, and Cellular Organelles

A set of Question-and-Answer flashcards covering key concepts from lipids, ketone bodies, lysosomal storage diseases, eicosanoids, cholesterol biosynthesis, and essential cell organelles and signaling mechanisms.

What is the basic structure of cholesterol?

A Perhydrocyclopentanophenanthrene (steroid) nucleus.

What is the major form of cholesterol found in plasma and where is it formed?

Cholesterol esters; formed intracellularly by ACAT and transported in lipoproteins.

Which enzyme esterifies cholesterol to form cholesterol esters (CE)?

Acyl-CoA-cholesterol acyl transferase (ACAT).

What is the primary site of de novo cholesterol synthesis and roughly what share does the liver contribute?

The liver; about 50% of total synthesis.

What is the starting molecule for cholesterol synthesis and how is acetyl-CoA made available in cytosol?

Starting molecule: acetyl-CoA. Citrate shuttle transports mitochondrial acetyl-CoA to the cytoplasm for synthesis.

What is the rate-limiting step of cholesterol synthesis?

Conversion of HMG-CoA to mevalonate by HMG-CoA reductase.

Which molecule provides the carbon backbone for cholesterol synthesis and which shuttle is involved?

Acetyl-CoA; citrate shuttle transports mitochondrial acetyl-CoA to the cytosol.

What are the main fates of cholesterol in the body?

Structural membrane component; precursor for steroid hormones, bile acids, and vitamin D.

What is a major takeaway about cholesterol esters (CE) in terms of hydrophobicity and transport?

CEs are more hydrophobic than free cholesterol and are transported in plasma within lipoproteins.

Which enzyme is inhibited by statins and what is the broader consequence beyond lowering cholesterol?

HMG-CoA reductase; statins also reduce intermediates like CoQ, possibly causing myopathy.

What enzyme converts HMG-CoA to mevalonate (the cholesterol synthesis rate-limiting step)?

HMG-CoA reductase.

Where are the enzymes for cholesterol synthesis located in the cell?

Cytosol and smooth endoplasmic reticulum (ER) fractions.

What is the rate-limiting enzyme in ketone body synthesis (ketogenesis) and where does this process occur?

HMG-CoA synthase (rate-limiting step); occurs in liver mitochondria.

What are the three main ketone bodies, and which is volatile and exhaled?

Acetoacetate, beta-hydroxybutyrate, and acetone; acetone is volatile and exhaled.

What conditions naturally raise ketone production and what can excessive levels cause?

Fasting/starvation or high fatty acid oxidation; excessive production can cause ketoacidosis.

Which tissues primarily utilize ketone bodies during fasting, and which tissue cannot utilize them?

Most tissues utilize ketones; the liver cannot use them (no thiophorase) and RBCs lack mitochondria to use ketones.

Where is the main site of ketogenesis and what substrates feed it?

Liver mitochondria; acetyl-CoA from fatty acid beta-oxidation and ketogenic amino acids (e.g., leucine, lysine) contribute.

What are the products and energy yield of full oxidation of one acetoacetate molecule?

Approximately 23 ATP (including 2 acetyl-CoA-derived ATP and losses from activation).

What are the products and energy yield of full oxidation of one beta-hydroxybutyrate molecule?

Approximately 26 ATP (NADH-derived energy plus acetyl-CoA contributions, minus activation).

What transcription factor regulates ketogenesis and how do insulin and glucagon modulate it?

FOXA2 regulates ketogenesis; glucagon activates FOXA2 to promote HMG-CoA synthase; insulin phosphorylates/exports FOXA2, decreasing HMG-CoA synthase expression.

How do ketone bodies aid in energy during fasting, and why is this advantageous?

They provide an energy source for extrahepatic tissues; offer a caloric yield (~5 kcal/g) and spare protein.

What is the energy yield per acetyl-CoA in the TCA cycle, and how many acetyl-CoA units come from palmitate (C16:0)?

About 10 ATP per acetyl-CoA; palmitate yields 8 acetyl-CoA (plus FADH2 and NADH contributions).

What are the major products of the cyclooxygenase (COX) pathway?

Prostaglandins (PGs), thromboxanes (TXA2), and prostacyclins (PGI2).

What is the difference between COX-1 and COX-2 enzymes?

COX-1 is constitutive (physiological functions); COX-2 is inducible (inflammation, pain, fever).

How do NSAIDs and aspirin modulate COX activity?

Aspirin irreversibly inhibits COX-1 and modestly affects COX-2; indomethacin and ibuprofen reversibly inhibit COX-1; coxibs selectively inhibit COX-2; corticosteroids inhibit phospholipase A2.

Which leukotriene is a potent chemotactic mediator and which prostanoid broadly mediates inflammation?

LTB4 (chemotaxis); PGE2 and other prostaglandins mediate inflammation and fever.

What is the precursor for eicosanoids and how is it released?

Arachidonic acid; released from membrane phospholipids by phospholipase A2 (PLA2).

What hallmark structure is associated with lysosomal storage diseases and what is the general mechanism?

Defective lysosomal enzymes leading to accumulation of undegraded substrates; LSDs are often autosomal recessive.

Describe Tay-Sachs disease (inheritance, enzyme deficiency, substrate, and distinguishing clinical feature).

Autosomal recessive; HEX A deficiency; GM2 ganglioside accumulation in neurons/retina; cherry-red spot; no hepatosplenomegaly.

Describe Niemann-Pick disease (deficiency, substrate accumulation, and distinguishing feature).

Sphingomyelinase deficiency; accumulation of sphingomyelin and cholesterol; hepatosplenomegaly.

Describe Gaucher disease (enzyme, substrate, and key clinical feature).

Glucocerebrosidase deficiency; glucocerebroside accumulation; hepatosplenomegaly; Gaucher cells (crumpled tissue paper).

What is I-cell disease and its key Golgi defect consequence?

Defect in N-acetylglucosaminyl-1-phosphotransferase; failure to add M6P tag; lysosomal enzymes secreted outside lysosome; severe multisystem disease.

Which lysosomal storage disease is most common, its enzyme, and typical tissue involvement?

Gaucher disease; glucocerebrosidase deficiency; hepatosplenomegaly, bone disease (Gaucher cells).

What are key functions of the rough endoplasmic reticulum (RER) and the Golgi apparatus?

RER: protein synthesis, folding, disulfide bonds, N-linked glycosylation, quality control; Golgi: further modify, sort, and package proteins/lipids; O-linked glycosylation; final sorting.

What is the unfolded protein response (UPR) and why is it important?

ER quality-control response that halts protein translation, upregulates chaperones, and enhances degradation; chronic ER stress can trigger apoptosis.

What is the ubiquitin–proteasome system (UPS) and how does it target proteins for degradation?

Misfolded/damaged proteins are polyubiquitinated (often via Lys48 linkages) and recognized by the 19S cap, unfolded, and degraded in the 20S core into short peptides (8–10 aa) and amino acids.

What is the core function of mitochondria and what inheritance pattern is characteristic of many mitochondrial disorders?

ATP production via oxidative phosphorylation; maternal inheritance (mtDNA).

Name two major components of the electron transport chain (ETC) carriers and the final electron acceptor.

Coenzyme Q (ubiquinone) and cytochromes; final electron acceptor is O2 (reduced to H2O).

Which molecule primarily determines passive diffusion rate across membranes and why?

Lipid solubility (solubility in the lipid bilayer) determines diffusion rate for small, nonpolar molecules.

What distinguishes primary from secondary active transport?

Primary uses direct energy from ATP hydrolysis; secondary uses energy stored in an ion gradient (often Na+) to drive transport.

Give an example of receptor-mediated endocytosis and its normal physiological outcome.

LDL uptake via LDL receptors; internalized into clathrin-coated pits, dissociation in endosomes, receptor recycling; cholesterol released in lysosomes.

What role do phospholipids play in membrane lipid asymmetry and signaling?

Outer leaflet: PC, SM, glycolipids; inner leaflet: PE, PS, PI; PS is negatively charged and flips to outer leaflet during apoptosis as a signal.