Fatty Acid Oxidation and Ketogenesis Flashcards
HDL
protective. More protein than fat, transports fat and cholesterol from peripheral circulation to liver.
LDL
higher % of fat and cholesterol than protein. Transports cholesterol from liver to peripheral circulation
Apolipoproteins ApoA1,2
Correlated with decrease heart disease even more than HDL
High ApoB + high ApoB/A1 ratio
correlates with cardiovascular risks.
Greatest Flux
Synthesis - Carb rich meals
Degradation - Starvation
Hormonal State
Synthesis - High insulin
Degradation - High Glucagon
Major tissues site
Synthesis - Liver
Degradation - muscle and liver
Sub cellular location
Synthesis - Citrate (Mitochondria to cytosol)
Degradation - Carnitine (cytosol to mitochondria)
Cofactors
Synthesis - NADPH
Degradation - NAD & FAD
Donor/Product
Synthesis - Malonyl CoA
Degradation - Acetyl CoA
Product of pathway
Synthesis - Palmitate
Degradation - Acetyl CoA
Mobilization
requires hydrolytic release of FA and glycerol
hormone-sensitive lipase
initiates, removes FA from C1 and or C3, di and mono acylglycerols have additional lipases for removing other FA
Glycerol
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
RBC
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
Fast
liver flooded with FA mobilized from adipose. High acetyl CoA produced –> inhibits pyruvate dehydrogenase –> activates pyruvate caroxylase –> produces oxaloacetate
Acetyl CoA synthesizes ketone bodies
Carnitime palmitoyltransferase I
1st acyl group is transferred from cytosolic CoA to carnitine
associated with the outer mitochondrial membrane
forms acyl-carnitine
regenerates free CoA
carnitine-acylcarnitine tanslocase
2nd acyl-carnitine transported into mitochondrion in exchange for free carnitine
Carnitime palmitoyltransferase II
associated with inner mitochondrial membrane
catalyzes transfer of acyl group from carnitine to CoA in mitochondrial matrix
regenerating free carnitine
Malonyl CoA
inhibits carnitine shuttle, and inhibits CPT-1
palmitate cannot get into the mitochondrial matrix
FA with less than 12 C
can cross the inner mitochondrial membrane without aid fo carnitine or CPT system.
Carnitine Sources
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
Fat of FA
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
Ketone bodies
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
Peripheral tissue energy source
ketone bodies
Ketones during fasting
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.
HMG CoA synthesis
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
Excessive Ketones
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
