Fatty Acid Oxidation and Ketogenesis

Question 1

HDL

Answer 1

protective. More protein than fat, transports fat and cholesterol from peripheral circulation to liver.

Question 2

LDL

Answer 2

higher % of fat and cholesterol than protein. Transports cholesterol from liver to peripheral circulation

Question 3

Apolipoproteins ApoA1,2

Answer 3

Correlated with decrease heart disease even more than HDL

Question 4

High ApoB + high ApoB/A1 ratio

Answer 4

correlates with cardiovascular risks.

Question 5

Greatest Flux

Answer 5

Synthesis - Carb rich meals

Degradation - Starvation

Question 6

Hormonal State

Answer 6

Synthesis - High insulin

Degradation - High Glucagon

Question 7

Major tissues site

Answer 7

Synthesis - Liver

Degradation - muscle and liver

Question 8

Sub cellular location

Answer 8

Synthesis - Citrate (Mitochondria to cytosol)

Degradation - Carnitine (cytosol to mitochondria)

Question 9

Cofactors

Answer 9

Synthesis - NADPH

Degradation - NAD & FAD

Question 10

Donor/Product

Answer 10

Synthesis - Malonyl CoA

Degradation - Acetyl CoA

Question 11

Product of pathway

Answer 11

Synthesis - Palmitate

Degradation - Acetyl CoA

Question 12

Mobilization

Answer 12

requires hydrolytic release of FA and glycerol

Question 13

hormone-sensitive lipase

Answer 13

initiates, removes FA from C1 and or C3, di and mono acylglycerols have additional lipases for removing other FA

Question 14

Glycerol

Answer 14

released during TAG degradation can’t be metabolized by adipocytes, due to lack of glycerol kinase, transports to liver to be phosphorylated, and used to form TAG or convert to DHAP

Question 15

RBC

Answer 15

cannot use fatty acids for fuel because they do not have a mitochondria. Also cannot be used by brain due to the blood brain barrier

Question 16

Fast

Answer 16

liver flooded with FA mobilized from adipose. High acetyl CoA produced –> inhibits pyruvate dehydrogenase –> activates pyruvate caroxylase –> produces oxaloacetate
Acetyl CoA synthesizes ketone bodies

Question 17

Carnitime palmitoyltransferase I

Answer 17

1st acyl group is transferred from cytosolic CoA to carnitine
associated with the outer mitochondrial membrane
forms acyl-carnitine
regenerates free CoA

Question 18

carnitine-acylcarnitine tanslocase

Answer 18

2nd acyl-carnitine transported into mitochondrion in exchange for free carnitine

Question 19

Carnitime palmitoyltransferase II

Answer 19

associated with inner mitochondrial membrane
catalyzes transfer of acyl group from carnitine to CoA in mitochondrial matrix
regenerating free carnitine

Question 20

Malonyl CoA

Answer 20

inhibits carnitine shuttle, and inhibits CPT-1

palmitate cannot get into the mitochondrial matrix

Question 21

FA with less than 12 C

Answer 21

can cross the inner mitochondrial membrane without aid fo carnitine or CPT system.

Question 22

Carnitine Sources

Answer 22

meat products
synthesized from amino acids lysine and methionine by enzymatic pathway found in liver and kidney
not in skeletal muscle or heart
tissues totally dependent on carnitine provided by hepatocytes or the diet and distributed by the blood

Question 23

Fat of FA

Answer 23

Move through the cell membrane of adipocytes to immediately bind to albumin in the plasma
Transported to the tissues
enters cells and activated by CoA

Question 24

Ketone bodies

Answer 24

mitochondria in liver convert acetyl CoA from FA oxidation to ketone bodies.
acetoacetate, 3-hydroxybutrate, and acetone
acetoacetate and 3-hydroxybutyrate transported from blood to peripheral tissues - source of energy
Reconverted to acetyl CoA. Oxidized in TCA cycle

Question 25

Peripheral tissue energy source

Answer 25

ketone bodies

Question 26

Ketones during fasting

Answer 26

liver is flooded with FA mobilized from adipose tissue high acetyl CoA produced inhibits pyruvate dehydrogenase and activates pyruvate carboxylase which produces oxaloacetate for gluconeogenesis. Acetyl CoA synthesizes ketone bodies.

Question 27

HMG CoA synthesis

Answer 27

form acetoacetyl CoA - reversal of thiolase reaction of FA oxidation. Mitochondrial HMG CoA synthase combines a third acetyl CoA with acetoacetyl CoA to produce HMG CoA. This is a limiting step of ketone synthesis. HMG CoA is precursor for cholesterol. Present only in liver. HMG CoA is cleaved to make acetoacetate and acetyl CoA. Acetoacetate reduced to 3-hydroxybutyrate. Spontaneously decarboxylated in blood for acetone. Breath smells sweet

Question 28

Excessive Ketones

Answer 28

ketones exceed use. Levels rise in blood ketonemia and urine ketonuria. Most seen in type 1 diabetics. high FA degradation produces excessive amounts of acetyl CoA - depleates NAD increase NADH slow TCA Excess acetyl CoA form ketone bodies Symptom fruity breath due to acetone Elevated ketone bodies in blood causes acidemia