Cholesterol Metabolism

What are the functions of cholesterol?

Steroid hormone synthesis

Bile acid production

Cell Membrane components

What is the substrate for cholesterol metabolism?

Acetyl CoA

What are the coenzymes for the cholesterol metabolism pathway?

ATP and NADPH

What are the products of cholesterol metabolism?

Cholesterol, ubiquinone

What is the rate-limiting enzyme of cholesterol?

HMG CoA Reductase

What coenzyme is needed for step 1 of cholesterol production?

NADPH

What is the product of step 1 of cholesterol production?

Mevalonate

What is the product of step 2 of cholesterol production?

Activated Isoprenes

What is the coenzyme for stage two of cholesterol production?

ATP

What is the product of step 3 of cholesterol production?

Squalene

What is the coenzyme of step 4 of cholesterol production?

NADPH

What is the product of step 4 of cholesterol production?

Steroid nucleus and cholesterol

What enzyme in stage 1 of cholesterol metabolism combines two molecules of Acetyl CoA to make Acetoacetyl CoA?

Thiolase

What enzyme in stage 1 of cholesterol metabolism produces HMG CoA from Acetoacetyl CoA and Acetyl CoA?

HMG-CoA Synthase

In what stage is the rate-limiting enzyme of cholesterol production found?

1

What is the product of the rate-limiting enzyme of cholesterol production?

Mevalonate

What inhibits HMG CoA reductase?

Increase in cholesterol productions

How does low blood sugar regulate HMG CoA reductase?

Activate glucagon, which activates PKA, which phosphorylates HMG CoA Reductase

What happens when HMG CoA reductase is phosphorylated?

Turns it OFF

How does high blood sugar activate HMG CoA reductase?

Insulin is secreted, PP1 is activated, which dephosphorylates HMG CoA reductase.

What happens when HMG CoA reductase is dephosphorylated?

Turns it ON

How do statins work?

Competitive inhibitors of the HMG-CoA reductase enzyme, which reduces cholesterol production in the liver.

What happens when cholesterol production in the liver is decreased?

Increased LDL receptors in liver, and cholesterol is delivered from blood and tissues to the liver.

What supplement is needed to decrease the muscle side effects of statins?

Coenzyme Q10 (ubiquinone or ubiquinol)

What can worsen statin side effects?

Vitamin D deficiency

High doses of niacin

What 3 components make up the traditional risk assessment for CVD?

Family history of CVD

Medial and lifestyle history

Serum lipid tests

What five tests are done in a traditional lipid panel?

Total cholesterol

HDL cholesterol

LDL cholesterol (calculated)

Cholesterol/HDL ratio (calculated)

Triglycerides

What are the four functional or independent risk markesr for CVD?

Genetic susceptibility

Nutritional deficiencies

Chronic inflammation

Tendency to coagulate

What is a test run for genetic susceptibility for CVD?

ApoA/AboB, Lipoprotein a, LDL subclasses and density

What is a test run for nutritional deficiencies related to CVD?

Homocysteine

Why can homocysteine be elevated?

low B6/B12 and folate

What is a test run for chronic inflammation when looking for CVD risk factors?

hsCRP

What test for coagulation tendency can be run to assess for CVD risk?

Fibrinogen (non-specific)

Name the three types of ketone bodies.

Acetone, acetoacetate, and beta-hydroxybutyrate

Which ketone bodies can be used as an energy source?

Acetoacetate and beta-hydroxybutyrate

What tissues CANNOT use fatty acids as source and need either glucose or ketone bodies?

Brain and nervous system

What are some reasons that someone would produce ketones?

Fasting

Keto diets

Carb restriction

Starvation

Inability to metabolize/utilize glucose (Type 1 DM)

What enzyme is used to make acetoacetate from HMG-CoA?

HMG-CoA lyase

What enzyme converts acetoacetate into acetone?

Acetoacetate decarboxylase

What enzyme converts acetoacetate into beta-hydroxybutyrate?

beta-hydroxybutyrate dehydrogenase

What is different between cholesterol production and ketogenesis?

HMG CoA reductase and NADPH are used in cholesterol production

HMG CoA lyase is used in ketogenesis

What is the substrate for ketogenesis?

Acetyl CoA

What ketone is exhaled?

Acetone

What happens when acetoacetate and beta-hydroxybutyrate are found in excess?

Ketoacidosis

What is the fuel source for ketolysis?

beta-hydroxybutyrate

What enzyme is required to go from beta-hydroxybutyrate back to acetoacetate?

PHB dehydrogenase

What enzyme is needed to go from acetoacetate to acetoacetyl CoA?

transferase

What other molecule is needed with the transferase molecule to go from acetoacetate to acetoacetyl CoA?

Succinyl CoA

How can you tell soemone is in ketosis?

Smell the acetone on their breath/skin

What population is ketoacidosis most problematic for?

Type 1 DM

Alcoholics

Issues with oxaloacetate regeneration

Prolonged starvation