Biochemistry test 2

In what form is cholesterol stored within tissues?

Combined with a long-chain fatty acid as a cholesteryl ester.

Why is cholesterol described as an amphipathic lipid?

It contains both hydrophilic and hydrophobic properties, allowing it to be a structural component of membranes.

What molecule serves as the source of all carbon atoms in synthesized cholesterol?

Acetyl-CoA.

Where does the biosynthesis of cholesterol primarily occur within the cell?

In the endoplasmic reticulum and the cytosol.

Which cytosolic enzyme catalyzes the initial condensation of two acetyl-CoA molecules into acetoacetyl-CoA?

Thiolase.

Which enzyme converts acetoacetyl-CoA and a third acetyl-CoA into 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)?

HMG-CoA synthase.

What is the principal regulatory step in the cholesterol biosynthesis pathway?

The reduction of HMG-CoA to mevalonate catalyzed by HMG-CoA reductase.

Which cofactor is required for the reduction of HMG-CoA to mevalonate?

NADPH.

Which class of drugs acts as inhibitors of HMG-CoA reductase to lower plasma cholesterol?

Statins (e.g., atorvastatin, simvastatin).

The formation of the active isoprenoid unit, isopentenyl diphosphate, requires the sequential phosphorylation of mevalonate by how many ATP molecules?

Three.

Which ten-carbon intermediate is formed by the condensation of isopentenyl diphosphate and dimethylallyl diphosphate?

Geranyl diphosphate.

The condensation of geranyl diphosphate with a second isopentenyl diphosphate molecule produces which 15-carbon intermediate?

Farnesyl diphosphate.

Which 30-carbon hydrocarbon is formed by the head-to-head condensation of two farnesyl diphosphate molecules?

Squalene.

Which enzyme is responsible for the cyclization of squalene 2,3-epoxide to lanosterol?

Oxidosqualene:lanosterol cyclase.

What is the first steroid produced in the cholesterol synthesis pathway?

Lanosterol.

Which 24-carbon intermediate is formed from lanosterol before the final reduction to cholesterol?

Desmosterol.

Besides cholesterol, farnesyl diphosphate serves as a precursor for which polyisoprenoid involved in N-glycosylation of proteins?

Dolichol.

Which component of the mitochondrial respiratory chain is synthesized using farnesyl diphosphate?

Ubiquinone (Coenzyme Q).

What is the physiological purpose of protein prenylation (attachment of farnesyl or geranylgeranyl residues)?

To facilitate the anchoring of proteins into lipoid membranes.

How does dietary cholesterol affect hepatic HMG-CoA reductase activity?

It inhibits the activity of the enzyme to reduce endogenous synthesis.

Which hormone increases the activity of HMG-CoA reductase?

Insulin (or thyroid hormone).

Which hormone decreases the activity of HMG-CoA reductase via cAMP-dependent mechanisms?

Glucagon (or glucocorticoids).

What is the effect of phosphorylation on HMG-CoA reductase activity?

It inactivates the enzyme.

Which specific apoprotein on the LDL particle is recognized by the LDL receptor?

Apo B-100.

How does an influx of cholesterol into the cell via the LDL receptor affect the cellular activity of ACAT?

It stimulates ACAT activity to promote cholesterol esterification for storage.

What is the primary role of the scavenger receptor (SR-B1) in reverse cholesterol transport?

Facilitating the uptake of cholesteryl esters from HDL into the liver.

Which enzyme, associated with HDL, is responsible for the esterification of free cholesterol in plasma?

LCAT (lecithin:cholesterol acyltransferase).

What is the function of the ABC-1 (ATP-binding cassette transporter A1) protein?

It moves cholesterol out of cells to allow for the lipidation of preβ-HDL.

Which protein facilitates the exchange of cholesteryl esters from HDL for triacylglycerols from VLDL or LDL?

CETP (cholesteryl ester transfer protein).

What are the two primary bile acids synthesized in the human liver?

Cholic acid and chenodeoxycholic acid.

Which enzyme catalyzes the rate-limiting step in bile acid biosynthesis?

Cholesterol 7α-hydroxylase.

Bile acid synthesis is feedback-inhibited by which nuclear receptor when bile acid levels are high?

Farnesoid X receptor (FXR).

Into which two amino acids are bile acids typically conjugated in the liver before secretion?

Glycine and taurine.

Which secondary bile acid is formed by the bacterial deconjugation and 7α-dehydroxylation of cholic acid?

Deoxycholic acid.

Which secondary bile acid is formed from the bacterial metabolism of chenodeoxycholic acid?

Lithocholic acid.

Approximately what percentage of bile acids secreted into the gut are reabsorbed in the ileum?

98%-99%.

What is the principal sterol found in feces?

Coprostanol.

Which lipoprotein deficiency is characterized by the absence of apo B-containing lipoproteins (chylomicrons, VLDL, LDL)?

Abetalipoproteinemia.

What is the molecular defect in Tangier disease?

A defect in the ABC-1 transporter, leading to a near absence of HDL.

Which type of hyperlipoproteinemia is caused by a deficiency in the LDL receptor?

Familial hypercholesterolemia (Type IIa).

What is the mechanism of action for the drug cholestyramine in lowering cholesterol?

It binds bile acids in the gut, preventing their reabsorption and forcing the liver to use more cholesterol for bile acid synthesis.

Why can fatty acids never be used for the net synthesis of glucose in humans?

The pyruvate dehydrogenase reaction is irreversible, and the two carbons entering the citric acid cycle are lost as CO₂ before oxaloacetate is reached.

Which two amino acids are exclusively ketogenic and cannot be used for gluconeogenesis?

Lysine and leucine.

What is the Respiratory Quotient (RQ) for the oxidation of fat?

0.71.

In the starving state, which tissue is the brain able to utilize for up to 20% of its energy requirements?

Ketone bodies.

Which metabolic fuel are erythrocytes entirely reliant upon due to their lack of mitochondria?

Glucose (via anaerobic glycolysis).

Which enzyme in the liver has a high Km for glucose, ensuring hepatic glucose uptake increases with portal blood glucose concentrations?

Glucokinase.

In adipose tissue, which enzyme is inhibited by insulin to prevent the release of free fatty acids?

Hormone-sensitive lipase.

What is the primary substrate for gluconeogenesis provided by the breakdown of triacylglycerols in adipose tissue?

Glycerol.

Why does the liver increase its production of ketone bodies during starvation?

It produces more acetyl-CoA from β-oxidation than can be oxidized in the citric acid cycle.

Which organ is the primary site for the urea cycle and the synthesis of plasma proteins?

The liver.

In the heart muscle, what is the order of preference for metabolic fuel oxidation?

1. Ketone bodies; 2. Fatty acids; 3. Glucose.

What is the metabolic significance of the Glucose-6-phosphatase enzyme in the liver?

It allows the liver to release free glucose into the blood for use by other tissues.

What condition results when the demand for glucose by a fetus or for milk production exceeds the body's capacity for gluconeogenesis?

Ketosis (or hypoglycemia).

Why is oxaloacetate availability critical for preventing ketosis?

It is required to condense with acetyl-CoA to enter the citric acid cycle; its depletion diverts acetyl-CoA to ketogenesis.

Which apoprotein is the primary activator of LPL (lipoprotein lipase)?

Apo C-II.

Which clinical condition is associated with a deficiency in remnant clearance due to an abnormality in Apo E?

Familial type III hyperlipoproteinemia (broad beta disease).

Which vitamin serves as a cofactor for cholesterol 7α-hydroxylase?

Vitamin C.

What is the effect of polyunsaturated fatty acids on LDL receptor expression compared to saturated fatty acids?

Polyunsaturated fatty acids up-regulate LDL receptors.

In the integration of metabolism, which tissue serves as the 'service organ' for other tissues by processing various substrates?

The liver.