Harper's Biochemistry Chapter 26 - Cholesterol Synthesis, Transport, & Excretion

The process of creating cholesterol in cells, tightly regulated at the HMG-CoA reductase step.

An enzyme that plays a critical role in cholesterol synthesis. Its activity is controlled to maintain proper levels.

The process of controlling the activity of HMG-CoA reductase to maintain cholesterol levels.

The immediate product of the reaction catalyzed by HMG-CoA reductase. It inhibits cholesterol synthesis.

Cholesterol, the main product of the cholesterol synthesis pathway, regulates HMG-CoA Reductase activity by inhibiting it.

A family of proteins that regulate transcription of genes related to cholesterol and lipid metabolism.

The process of stimulating SREBPs; inhibited by insulin-induced protein (Insig).

A protein that inhibits SREBP activation and promotes HMG-CoA Reductase degradation, expression induced by insulin.

The process by which cells take in cholesterol from lipoproteins (like LDL) or through other means.

A receptor on cells that binds to low-density lipoproteins (LDL) to take up cholesterol.

The process of cholesterol leaving a cell, often to HDL (high-density lipoprotein).

The process of converting cholesterol to cholesteryl esters, making it storable.

An enzyme that breaks down cholesteryl esters, releasing cholesterol.

An enzyme crucial for cholesterol synthesis; its activity is regulated by cholesterol levels.

A cellular pathway that regulates the expression of genes involved in cholesterol synthesis and uptake, in response to cholesterol levels.

A protein that regulates receptor recycling by targeting it for degradation, thus affecting LDL receptor activity.

Insulin plays a key role in regulating cholesterol synthesis, influencing the activity of HMG-CoA reductase more prominently than glucagon.

HMG-CoA reductase activity is controlled through phosphorylation/dephosphorylation, potentially involving cAMP-dependent mechanisms, responding to factors like glucagon.

AMP-activated protein kinase (AMPK) phosphorylates and inactivates HMG-CoA reductase, influenced by AMPKK and AMP levels.

Glucagon, in contrast to insulin, generally decreases HMG-CoA reductase activity.

The LDL receptor (apo B-100, E) on cell surfaces takes up LDL via endocytosis after binding.

LDL receptors are located on the cell surface in pits coated with clathrin.

LDL receptors are glycoproteins spanning the cell membrane, with the B-100 binding region exposed.

The creation of cholesterol within the body.

Key enzyme in cholesterol synthesis.

Creating cholesterol from scratch within the body.

Cholesterol consumed from food.

Changes to an enzyme after it's made.

Hormone that regulates many metabolic processes.

Enzyme involved in energy balance

Quick modifications to enzyme functions

Hormone that regulates blood sugar levels.

Low-density lipoprotein cholesterol, a type of cholesterol.

A key intermediate in cholesterol biosynthesis. A crucial molecule in the pathway.

A precursor molecule in cholesterol synthesis, made from isopentenyl diphosphate.

The process of creating cholesterol from acetyl-CoA.

A crucial molecule in cholesterol synthesis created using HMG-CoA.

A key component in various biological processes, a precursor to dolichols, and ubiquinones.

A type of isoprenoid essential for protein glycosylation and lipid transport.

A crucial molecule in the electron transport chain (ETC), important for energy transfer.

An enzyme that catalyzes the synthesis of squalene from farnesyl diphosphate.

3-Hydroxy-3-methylglutaryl-CoA, a key intermediate in cholesterol synthesis.

A 27-carbon compound with four rings and a side chain, crucial for cell membranes and hormones.

Source of carbon atoms for cholesterol synthesis.

Product of HMG-CoA reductase, a crucial step in cholesterol synthesis.

Enzyme that catalyzes the conversion of HMG-CoA to mevalonate.

Building blocks derived from mevalonate, crucial for making larger molecules like squalene.

A long chain molecule made from six isoprenoid units, a precursor to cholesterol.

Creation of cholesterol from acetyl-CoA through multiple steps.

A key enzyme in cholesterol synthesis, its activity is tightly regulated.

The process of controlling cholesterol production in cells by managing HMG-CoA Reductase activity.

Mevalonate, the immediate product of the reaction, and cholesterol.

Proteins that regulate gene expression for cholesterol and lipid metabolism.

Blocked by Insulin-induced gene (Insig) which increases with insulin and is found in the endoplasmic reticulum.

A protein that inhibits SREBP activation and promotes HMG-CoA reductase degradation.

Cholesterol inhibits transcription of HMG-CoA reductase mRNA, affecting SREBP activity.

Two acetyl-CoA molecules combine to form acetoacetyl-CoA, catalyzed by cytosolic thiolase.

The process of controlling the rate of cholesterol production in the body, primarily through adjustments to the HMG-CoA reductase enzyme.

Acetoacetyl-CoA combines with another acetyl-CoA, creating HMG-CoA, catalyzed by HMG-CoA synthase.

A key enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a crucial step in cholesterol synthesis.

HMG-CoA is reduced to mevalonate by NADPH, catalyzed by HMG-CoA reductase.

Insulin predominantly inhibits de novo cholesterol synthesis by affecting HMG-CoA reductase activity, compared to glucagon.

Enzyme catalyzing the conversion of HMG-CoA to mevalonate; a key regulatory step in cholesterol synthesis, targeted by statins.

AMP-activated protein kinase (AMPK) inhibits HMG-CoA reductase by phosphorylation as part of cellular energy regulation.

Mevalonate is phosphorylated, then decarboxylated to form isopentenyl diphosphate, an essential isoprenoid unit.

Increased dietary cholesterol intake reduces the body's de novo synthesis of cholesterol, primarily in the liver.

Changes to an enzyme after it's created, impacting its activity. Examples include phosphorylation.

Multiple isopentenyl diphosphate molecules combine to form squalene, a crucial precursor to cholesterol.

Enzyme that converts squalene to squalene 2,3-epoxide; crucial for the next stage of cholesterol synthesis.

Squalene folds to create the steroid nucleus; then squalene epoxide forms Lanosterol through the enzyme oxidosqualene-lanosterol cyclase.

Lanosterol undergoes further modification (methyl group removal, and double bond rearrangements) to form cholesterol in the endoplasmic reticulum.

Insulin has a dominant role compared to glucagon in regulating cholesterol synthesis, primarily affecting HMG-CoA reductase activity.

HMG-CoA Reductase activity is controlled by phosphorylation/dephosphorylation, potentially cAMP-dependent, that responds to glucagon and other factors.

AMP-activated protein kinase (AMPK) phosphorylates and inactivates HMG-CoA reductase, modulated by AMPK kinase and AMP levels.

Glucagon generally decreases HMG-CoA reductase activity as opposed to insulin's effects.

The LDL receptor (apo-B100, E) on cell surfaces takes up LDL via endocytosis after binding.

LDL receptors are located on cell surfaces in pits lined with clathrin.

LDL receptors are glycoproteins crossing the cell membrane, with the B-100-binding site on the exposed amino end.

Enzyme that combines two acetyl-CoA molecules to form acetoacetyl-CoA.

About 70% of cholesterol is produced in the body from acetyl-CoA.

Cholesterol is synthesized in the endoplasmic reticulum and cytosol of cells.

Liver and intestine account for about 10% each of total cholesterol synthesis in humans.

Cholesterol is a vital structural component of cell membranes and a precursor for steroid hormones.

Cholesterol is created in five stages from acetyl-CoA.

A crucial enzyme that controls the rate of cholesterol synthesis.

High cholesterol levels are a major risk factor for atherosclerosis, a disease leading to artery hardening.

Plasma lipoproteins (like VLDL, LDL, HDL) carry cholesterol between body tissues.

Primary bile acids are synthesized from cholesterol in the liver.

Bile acid synthesis is important for fat digestion and cholesterol excretion.

Bile acids circulate between the intestine and liver, improving efficiency.

Diet, lifestyle, and lipoprotein types impact plasma cholesterol levels and heart disease risk.