Chapter 21: Lipid Metabolism

Acetyl-CoA, NADH, FADH2

Metabolic oxidation of lipids releases large quantities of energy through production of _____

Oxidation of fatty acids

Chief source of energy for catabolism of lipids

Triacylglycerol

• Main storage form — lipids

• Carbon chains in highly reduced form

• Energy yield per g fatty acid > per g of carbohydrate oxidized

Phosphoacylglycerol

• Key component of biological membranes

• Have multiple sites of action

Lipases

Enzyme that hydrolyzes lipids

Phospholipases

Enzyme that hydrolyzes phospholipids

Carboxyl group; thiol group

Activation in lipid metabolism: Thioester bond is formed between the

_____ of the fatty acids and the _____ of CoA-SH

Acyl-CoA synthetase

Catalyzes formation of the ester bond in fatty acid activation and requires ATP for its action

Cytosol

Esterification takes place in the _____

Mitochrondrial matrix

Fatty acid oxidation occurs in the _____

Acyl-CoA

It can cross the outer mitochondrial membrane but not the inner membrane

Carnitine

Molecule used in fatty acid metabolism to shuttle acyl groups across the inner mitochondrial membrane

Carnitine acyltransferase

Enzymes that transfer a fatty acyl group to carnitine

Carnitine palmitoyltransferase I (CPT-I)

Type of carnitine acyltransferase — found on the cytosol side of the inner mitochondrial membrane with a specificity for acyl groups between 14-18 carbons long

Carnitine palmitoyltransferase II (CPT-II)

Type of carnitine acyltransferase — found on the mitochondrial matrix

β-oxidation

Repeated series of reactions that cleaves two-carbon units from the carboxyl end

of a fatty acid

Acyl-CoA dehydrogenase; Oxidation

Enzyme and Reaction: Acyl-CoA → Unsaturated acyl-CoA (trans-Enoyl-CoA )

Enoyl-CoA hydratase; Hydration

Enzyme and Reaction: Unsaturated acyl-CoA (trans-Enoyl-CoA) → β-hydroxyacyl-CoA

β-hydroxyacyl-CoA dehydrogenase; Oxidation

Enzyme and Reaction: β-hydroxyacyl-CoA → β-ketoacyl-CoA

Thiolase; Cleavage

Enzyme and ReactionL: β-ketoacyl-CoA → Acyl-CoA

8

How many cycles of β-oxidation are required for the oxidation of 1 mole of stearic acid to 9 moles of acetyl-CoA?

TCA Cycle

Nine moles of acetyl-CoA produced from each mole of stearic acid enter the _____

ETC; oxidative phosphorylation

FADH2 and NADH produced by β-oxidation and the citric acid cycle enter the _____, and ATP is produced by _____

Propionyl-CoA

Last β-oxidation cycle of odd-carbon fatty acids gives _____

Cis-trans isomerization

_____ is needed to convert monounsaturated fatty acids to acetyl-CoA

Saturated

(Unsaturated/Saturated) fatty acids generate more ATPs

Ketone bodies

Formed when the amount of acetyl-CoA produced is excessive when compared to the amount of oxaloacetate available to react with it

Acetyl-CoA

Starvation causes an organism to break down fats for energy, leading to the production of large amount of _____ by β-oxidation

Inadequate intake of carbohydrates

In diabetic patients, cause of imbalance is _____

Liver mitochondria

Ketone bodies are formed principally in _____

Acetone, β-hydroxybutyrate, acetoacetate

Ketone bodies

Acetoacetate

Can be used as a fuel in most tissues and organs (preferred by heart muscle and renal cortex)

Acetoacetyl-CoA

The reactions that result in ketone bodies start with the condensation of two molecules of acetyl-CoA to produce _____

β-hydroxybutyrate

Reduction of acetoacetate produces _____

Acetone

Spontaneous decarboxylation of acetoacetate produces _____

Acetone

Its odor can be detected on the breath of people with diabetes

Ketosis

A pathological condition where there is an excess of acetoacetate, and consequently of acetone

Acetoacetate and β-hydroxybutyrate

Acidic; presence at high concentration overwhelms the buffering capacity of the blood

Ketoacidosis

Lowering of blood PH due to high concentration of acetoacetate and β-hydroxybutyrate overwhelming the buffering capacity of blood

Cytosol

Anabolic reactions occur in the _____

Acetyl-CoA

Can be either formed by β-oxidation of fatty acids or by decarboxylation of pyruvate

Acetyl-CoA carboxylase complex; Carboxylation

Enzyme and Reaction: Acetyl-CoA → malonyl-CoA

Mn2+, biotin, ATP

Acetyl-CoA carboxylase complex requires _____

Biotin

Carrier of the carboxyl group and an important cofactor in the carboxylation of acetyl-CoA in the cytosol

Glycerol-3-phosphate

Glycerol portion of lipids is derived from _____

Phosphatidates

Phosphoacylglycerols are based on _____, with the phosphate group esterified to another alcohol

Sphingosine

Structural basis of sphingolipids; a long chain amine

Palmitoyl-CoA and serine

Biosynthesis of sphingolipids requires _____ and _____

Acetyl group

All carbon atoms of cholesterol and steroids synthesized from cholesterol are derived from the two-carbon _____ of acetyl-CoA

Cholesterol

Steroid that occurs in cell membranes and is the precursor of other steroids

Involvement of isoprene units

Key to the biosynthesis of steroids

Isoprene units

Five-carbon groups that are used in biosynthesis of steroids

Condensation of 2 acetyl-CoA molecules

1st step of cholesterol biosynthesis

HMG-CoA synthetase; Condensation

Enzyme and Reaction: Acetyl-Coa + Acetoacetyl-CoA → β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)

HMG-CoA reductase; Reduction of thioester

Enzyme and Reaction: HMG-CoA → Mevalonate

Mevalonate kinase

Enzyme for: Phosphorylation of 1º alcohol of mevalonate (2 ATP)

Phosphomevalonate kinase

Enzyme for: Phosphorylation of 3º alcohol of mevalonate (1 ATP)

Isopentenyl pyrophosphate isomerase; Isomerization

Enzyme and Reaction: Isopentenyl pyrophosphate → Dimethylallyl pyrophosphate

Squalene

Two molecules of farnesyl pyrophosphate (C₁₅) condense to form _____

Lanosterol

Cholesterol is synthesized from squalene via _____

7-dehydryocholesterol to cholesterol

The last step of the primary route from lanosterol converts _____ to _____

Desmosterol

An alternative route from lanosterol to cholesterol produces _____ as the penultimate intermediate

Squalene monooxygenase

Catalyzes squalene → squalene epoxide

• Requires NADPH and O2

Squalene epoxide cyclase

Catalyzes the cyclization of squalene epoxide to form lanosterol

Pregnenolone

Formed from cholesterol and produces progesterone

• Progesterone is a precursor for testosterone and estradiol

Cortisone

An example of glucocorticoids

Aldosterone

An example of mineralocorticoids

Low-density lipoproteins (LDLs)

Class of lipoprotein

• Transports cholesterol from liver to the rest of the body

• bad cholesterol

High-density lipoproteins (HDLs)

Class of lipoproteins

• Transports cholesterol back to the liver for degradation to bile acids

• good cholesterol

LDL, HDL

High _____ and low _____ correlate with the development of heart disease

NPY/AgRP-producing neurons

Stimulate eating and produce neuropeptide Y (NPY)

Melanocortin producing neurons

Inhibit eating

Ghrelin and cholecystokinin

Regulators of short-term effects of eating

Insulin and leptin

Involved in long-term control of eating