β-oxidation, ketogenesis, fatty acid synthesis, lipoprotein metabolism, cholesterol synthesis

Flashcards for β-oxidation, ketogenesis, fatty acid synthesis, lipoprotein metabolism, and cholesterol synthesis.

β-oxidation

Mitochondrial pathway that generates acetyl-CoA, NADH, and FADH2 from the oxidation of free fatty acids.

Ketogenesis

Mitochondrial pathway that generates ketones from excess acetyl-CoA produced from β-oxidation.

Lipolysis

Process of releasing free fatty acids from triacylglycerols stored in the adipose tissue.

Hormone-sensitive lipase

Enzyme activated by glucagon and epinephrine that hydrolyzes triacylglycerols into free fatty acids and glycerol.

Acyl-CoA synthetase

Enzyme that adds an acyl-CoA to free fatty acids, converting them to fatty acyl-CoAs.

Carnitine palmitoyl transferase I (CPTI)

Enzyme that transfers fatty acyl-CoAs to carnitine, generating fatty acyl-carnitine for transport into the mitochondria.

Malonyl-CoA

Inhibitor of carnitine palmitoyl transferase I (CPTI).

Acetyl-CoA

Product of β-oxidation that can be used for ketogenesis, allosteric activation of pyruvate carboxylase, or the TCA cycle.

HMG-CoA synthase

Enzyme that generates HMG-CoA in the ketogenesis pathway.

HMG-CoA lyase

Enzyme that cleaves HMG-CoA into acetyl-CoA and acetoacetate.

Acetoacetate

Ketone body that can be reduced to D-3 hydroxybutyrate or spontaneously decarboxylated to acetone.

D-3 hydroxybutyrate (β-hydroxybutyrate)

Ketone body produced from the reduction of acetoacetate.

Ketoacidosis

Condition that can occur from prolonged ketogenesis, resulting from starvation or uncontrolled diabetes.

Fatty acid synthesis

Cytosolic process activated by insulin and inhibited by glucagon that produces fatty acids.

Citrate lyase

Enzyme that cleaves citrate in the cytosol, producing OAA and acetyl-CoA.

Acetyl-CoA carboxylase

Regulatory enzyme in fatty acid synthesis that converts acetyl-CoA to malonyl-CoA.

Fatty acid synthase

Multimeric enzyme that synthesizes C-16 palmitate.

Acyl-carrier protein (ACP)

Subunit of fatty acid synthase that is initially primed by acetyl-CoA and requires pantothenic acid as a cofactor.

Palmitate

Final product of fatty acid synthase.

Thioesterase

Enzyme that releases palmitate from fatty acid synthase.

VLDL

Lipoprotein that transports fatty acids synthesized in the liver to adipose tissue.

Lipoprotein

Particles that transport lipids in the blood.

HDL

Lipoprotein that plays a primary role in reverse cholesterol transport.

LDL

Lipoprotein that transports cholesterol from the liver.

VLDL

Lipoprotein that carries newly synthesized TAG from the liver to the adipose tissue.

Chylomicron

Lipoprotein that carries dietary lipids to the adipose tissue for storage.

ApoB100

Apoprotein found on LDL and VLDL.

ApoB48

Apoprotein found on chylomicrons.

ApoA

Apoprotein found on HDL.

ApoCII

Apoprotein that interacts with LPL to activate the enzyme.

ApoE

Apoprotein on chylomicrons and VLDL used for uptake by the liver.

LPL (lipoprotein lipase)

Enzyme on vascular epithelium that cleaves triacylglycerols into glycerol and free fatty acids.

ACAT (acyl-CoA‒cholesterol acyl transferase)

Enzyme that catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol.

CETP (Cholesteryl ester transfer protein)

Protein that transfers cholesteryl ester from HDL to VLDL and transfers TG from VLDL to HDL.

LDL Receptor

Receptor that binds ApoB100 on LDL particles and facilitates the uptake of LDL particles.

SR1 (Scavenger receptor)

Receptor on liver cells that functions in HDL particle uptake.

Microsomal transfer protein (MTP)

Protein involved in the loading of ApoB proteins on to both chylomicrons (in the intestine) and VLDL in the liver.

Abetalipoproteinemia

Genetic disorder characterized by loss of the ability to form lipoproteins containing ApoB, leading to a loss of chylomicrons and VLDL.

Familial hypercholesterolemia

Genetic disorder characterized by loss of LDL receptor, leading to increased LDLs in circulation and elevated cholesterol.

Cholesterol synthesis

Cytosolic process in which Acetyl-CoA is the source of all carbons in cholesterol synthesis

HMG-CoA reductase

Regulatory enzyme in cholesterol synthesis.

SREBP (Sterol response element-binding protein)

Transcription factor that activates HMG-CoA reductase.

Insig

Protein that binds SREBP and retains it in the ER, inhibiting HMG-CoA reductase.

PCSK9

Protein that mediates degradation of the LDL receptor.

Statins

Class of drugs that inhibit HMG-CoA reductase.

Cholesterol 7 α-hydroxylase

Regulatory step in bile acid synthesis.

Primary bile acids

Cholic acid and chenodeoxycholic acid.

β-oxidation regulation

β-oxidation regulated by CPT1; inhibited by Malonyl-CoA

Insulin effect on fatty acid synthesis

Insulin activates fatty acid synthesis

Glucagon effect on fatty acid oxidation

Glucagon stimulates lipolysis and fatty acid β-oxidation

Free fatty acids transport

Free fatty acids travel bound to albumin to peripheral tissues

Glycerol fate during lipolysis

Glycerol travels to the liver and used as a substrate for gluconeogenesis

Carnitine acylcarnitine translocase

Transporter that works to bind fatty acyl-carnitine moving it to the inner mitochondrial matrix and recycling carnitine

Products of β-oxidation spiral

Products are acetyl-CoA, NADH and FADH2

Ketones as fuel

Ketones can be used as fuel by other tissues but cannot be oxidized by the liver

Ketogenesis regulation

Ketogenesis regulated by activity of lipolysis, cytosolic levels of malonyl-CoA, and flux through the TCA

β-oxidation deficiencies

Deficiencies in β-oxidation can result in hypoglycemia due to inability to support glucose synthesis

Malate dehydrogenase

OAA is reduced to malate

Malic enzyme

Decarboxylates malate → pyruvate

Insulin effect on Acetyl-CoA carboxylase

Insulin activates Acetyl-CoA carboxylase

Glucagon effect on Acetyl-CoA carboxylase

Glucagon inhibits Acetyl-CoA carboxylase

PPP connection to fatty acid synthesis

The pentose phosphate pathway provides glycerol and NADPH

ABCG1/ABCA1 transporter

on the cell surface and is responsible for active transport of cholesterol and lipids out of the cell into the HDL particle

Chylomicrons role

Transport dietary lipids and fat-soluble vitamins

VLDL role

Transports fatty acids synthesized in the liver

LDL maturation

Maturation product of VLDL that retains ApoB100 and is largely filled with cholesterol ester

HDL origin

HDLs originate from the liver and intestine

Lipolysis regulation

Lipolysis is stimulated by epinephrine and inhibited by insulin.

Role of adipose in lipolysis

Adipose tissue stores triacylglycerols and releases free fatty acids during lipolysis.

Role of liver in lipolysis

Liver receives glycerol from lipolysis and uses it for gluconeogenesis

Regulation of CPT1

CPT1 is inhibited by malonyl-CoA.

Location of fatty acid oxidases

Fatty acid oxidases are found in the mitochondrial matrix.

Gluconeogenesis and Fatty acid Synthesis

ATP required for both glucose synthesis via gluconeogenesis

Urea Cycle and Fatty acid Synthesis

ATP is required for nitrogen disposal via the urea cycle

Activation of Acetyl-CoA carboxylase

Acetyl-CoA carboxylase is activated by insulin, citrate, and dephosphorylation.

Inhibition of Acetyl-CoA carboxylase

Acetyl-CoA carboxylase is inhibited by glucagon, palmitoyl-CoA, and phosphorylation.

Loading of ApoB proteins

Microsomal transfer protein (MTP) essential for the loading of ApoB proteins

Synthesis location of VLDL

Synthesized in the hepatocyte → released into circulation

Newly synthesized fatty acids

Newly synthesized fatty acids are packaged into VLDLs and released into circulation

VLDL receptor

VLDL receptor enhances hydrolyses TAGs

Function of SR-B1 receptor

Broken down into cholesterol, amino acids and glycerol

TAG measurement

TAG measurement is a proxy for VLDLs as they carry to greatest amount of TAG in circulation

Cholesterol excretion

Cholesterol is excreted primarily as unesterified cholesterol and bile acids

Location of Cholesterol synthesis

Cholesterol synthesis (cytosolic process)

Functions of Cholesterol

Used as a substrate for the synthesis of steroid hormones, sex hormones, bile acids, & Vitamin D

Source of carbons in Cholesterol synthesis

Acetyl-CoA

Most important stage of Cholesterol synthesis

Synthesis of mevalonate

Regulation of cholesterol synthesis

Mainly regulated by regulatory enzyme HMG-CoA reductase

Bile acid synthesis location

Majority of bile acids are reabsorbed in the ileum

ATP role - Summary

ATP is required for both the process of glucose synthesis via gluconeogenesis and nitrogen disposal via the urea cycle

acyl-CoA re-conversion

Acyl-CoA synthetase can re-convert free fatty acids to acyl-CoA which can be used for re-esterification in the adipose

Fatty acid oxidation - Primary tissue

Primarily liver and skeletal muscle

Fatty Acyl-Carnitine function

Fatty Acyl-Carnitine moving it to the inner mitochondrial matrix and recycling carnitine

Two ketone bodies

acetoacetate and D-3 hydroxybutyrate

Ketones and the brain

Brain will oxidize ketones during starvation states decreasing the reliance on glucose

Cytosolic process

Fatty acid synthesis is a cytosolic process

Tricarboxylate transporter

removes excess citrate from the mitochondria

Acyl-carrier location

Fatty acid synthase: multimeric enzyme that synthesizes C-16 palmitate

Interaction of Nascent chylomicron with HDL

Nascent chylomicron interacts with HDL in circulation so it gets a full complement of ApoE / ApoCII

Familial hypercholesterolemia

increases LDLs in circulation and elevated cholesterol