Lipid Metabolism

Question 1

How is Acetyl CoA transported from mitochondria to cytoplasm

Answer 1

It is converted to citrate in TCA cycle, then transported out via citrate transporter, then converted to Acetyl CoA and Oxaloacetate by ATP citrate lyase

Question 2

Allosteric regulators of citrate lyase include

Answer 2

Glucose, Insulin ++

PUFA, Leptin –

Question 3

What is the rate limiting step in FA synthesis

Answer 3

Conversion of Acetyl CoA to malonyl CoA by acetyl CoA carboxylase

Question 4

What is the series of reduction/condensation/dehydration events in FA synthesis

Answer 4

Condensation, reduction, dehydration, reduction

Question 5

Gene expression of FA synthesis genes is activated by what type of diet

Answer 5

High carb, low fat

Question 6

Allosteric regulators of Acetyl CoA carboxylase

Answer 6

Citrate, insulin +

Glucagon, epinephrine, AMP, PUFA, palmitate -

Question 7

Phosphorylation regulators of Acetyl CoA carboxylase

Answer 7

Insulin ++ activates protein phosphatase
Epinephrine/Glucagon – via PKA
AMP – via AMP kinase

Question 8

Where are fatty acids elongated, and what carbon donor is used for each area

Answer 8

SER- Malonyl CoA is carbon donor

Mitochondria- Acetyl CoA is carbon donor

Question 9

TAG synthesis in intestinal cells vs liver cells vs adipose- promoted by what in each area?

Answer 9

Intestinal- dietary TAGs, leave as chylomicrons
Liver- Excess carbs, leave as VLDL
Adipose- excess carbs and fat, leave as VLDL

Question 10

What is HSL and how is it regulated

Answer 10

Hormone sensitive lipase- Breaks down TAGs
Phosphorylated/activated by glucagon/epinephrine
Insulin dephosphorylates via PPI

Question 11

Perilipins do what

Answer 11

Regulate lipolysis by controlling physical access to HSL

PKA phosphorylates perilipin which then allows association with HSL

Question 12

How do fatty acids get into mitochondria

Answer 12

Fatty acid is attached to CoA in order to get through outer mito membrane (not permeable to FA)

• Then converted to FA-carnitine to get through inner mito membrane (not permeable to FA-CoA)
• Short/medium chain FA can diffuse through mito membrane, while long/very long cannot

Question 13

FA-CoA synthetase location/function

Answer 13

Located on outer mitochondrial membrane

Activates LCFA using ATP to form FACoA

Question 14

Carnitine palmitoyltransferase-I (carnitine acyltransferase) location/function

Answer 14

Intermembrane space of mitochondria
Transfers fatty acyl from FA-CoA to carnitine
-Rate limiting enzyme in FA breakdown
-Inhibited by malonyl CoA

Question 15

Carnitine palmitoyl/acyl-transferase II location/function

Answer 15

Inner mito membrane
Transfers FA from carnitine to CoA
FA-CoA now in mito matrix

Question 16

What are the 4 steps of beta-oxidation and their enzymes

Answer 16

Oxidation- Acyl CoA dehydrogenase
Hydration- Enoyl CoA hydratase
Oxidation- B hydroxy acyl CoA dehydrogenase
Thiolysis- Acyl CoA acyl transferase

Question 17

VLCFAs (greater than 20c) are metabolized where

Answer 17

In peroxisomes

Question 18

With odd numbered fatty acids, which molecule finally ends up entering the TCA cycle

Answer 18

Succinyl CoA

Question 19

What two enzymes are required for unsaturated fatty acid breakdown

Answer 19

Reductase (reduce double bond)

Isomerase (move disruptive bond)

Question 20

MCAD deficiency

Answer 20

Impairs breakdown of MCFAs
Leads to secondary carnitine deficiency, due to excessive excretion of MCA carnitines in urine
C8 FA accumulates in liver, poisonous, elevated levels of ammonia

Question 21

Name 3 ketone bodies and where they are produced

Answer 21

Acetoacetate
B-hydroxybutyrate
Acetone
Only produced in liver

Question 22

List off energy sources from the first one used to the last one used when fasting

Answer 22

Glucose
Glycogen
Gluconeogenesis in liver (new glucose made)
TAGs
Ketone bodies
AAs/glycerol

Question 23

Ketoacidosis

Answer 23

Occurs when glucagon/insulin ratio is increased, favoring FA breakdown
Increased acetyl CoA in hepatic mitochondria
Increased gluconeogenesis, reduced OAA, increased ketone bodies-blood pH lowers