Fatty Acid Oxidation Ketosis

Front 1

Compare the available energy per gram for carbs, protein, and fat

Back 1

4, 4, and 9

Front 2

General process by which fats are converted into energy?

Back 2

triacylglycerol is converted into f.a. > f.a. converted to acetyl CoA (produces FADH2 and NADH) > AcCoA enters TCA cycle > NADH for oxphos > ATP

Front 3

Why does a molecule of fat have more energy than a molecule of glucose?

Back 3

glucose is already partially oxidized, while fats are not, which is why fat has more energy.

Front 4

What form do dietary lipids take when they first enter the bloodstream?

Back 4

chylomicrons, large lipid particles that are transported to adipose tissue and muscle

Front 5

chylomicron: def. primarily composed of?

Back 5

large lipid particles; composed primarily of triacylglycerols (90%), as well as cholesterol, phospholipids, and protein

Front 6

Describe the process of chylomicron digestion. Include location, necessary enzymes, and products.

Back 6

chylomicron triglycerides => free f.a.'s + glycerol (enz is lipoprotein lipase). LPL is in capillary endothelium of muscle and adipose tissue.

Front 7

Which 3 lipases hydrolyze stored fat to release it into the bloodstream?

Back 7

1 adipose tissue triglyceride lipase (ATTL), 2 hormone sensitive lipase (HSL), 3 monoglyceride hydrolase (MH)

Front 8

HSL is activated by phosphorylation/dephosphorylation?

Back 8

phosphorylation

Front 9

Which signalling molecules stimulate the activation of lipases? Describe the mechanism.

Back 9

adrenaline, glucagon => inc cAMP => phactivates Hormone Sensitive Lipase (this one first because it is directly hormone sensitive) => activates Adipose Tissue Triglyceride Lipase and Monoglyceride Hydrolase

Front 10

What molecule transports fatty acids?

Back 10

serum albumin

Front 11

Where does fatty acid β-oxidation occur?

Back 11

mitochondria

Front 12

What event must occur before fa-beta-ox can occur? Where in the cell does this happen?

Back 12

f.a.'s must be activated by adding an acyl-CoA group (enz fatty acyl-CoA synthetase). Occurs in cytosol.

Front 13

Give a very general overview of what fatty acid β ox does

Back 13

breaks down fatty acids to yield acetyl CoA, as well as FADH2 and NADH.

Front 14

synthetase, def

Back 14

enzyme that requires high energy phosphate

Front 15

How do activated f.a.'s bound for fa-beta-ox get from the ______ (site of activation) to the ______ (site of fa-beta-ox)

Back 15

activation in cytosol, fa-beta-ox in mitoch matrix, transported via carnitine transport pathway

Front 16

describe the carnitine transport pathway. Include enz.

Back 16

1 fatty-acyl(ex. palmitoyl) CoA crosses outer mitoch membr, 2 enz carnitine palmitoyl transferrase I swaps carnitine for CoA group, 3 palmitoyl carnitine crosses membrane, 4 carnitine palmitoyl transferrase II swaps CoA for carnitine, 5 f.acyl-coA is released in matrix and carnitine crosses back to intermemb space

Front 17

Which kind of f.a.'s do NOT have to use the carnitine transport pathway?

Back 17

medium chain fatty acids

Front 18

How many ATP are generated by one turn of the fa-beta-ox cycle? (Counting the subsequent energy derived from oxphos)

Back 18

14 ATP

Front 19

CLINICAL APPLICATION: clinical outcome and treatment of deficiency in enzymes involved in the carnitine transport pathway

Back 19

results in hypoglycemia; treatment is to avoid fasting and sustained exercise

Front 20

CLINICAL APPLICATION: Describe the symptoms of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

Back 20

Same physiologic problems as people with carnitine deficiency, cannot efficiently metabolize fatty acids and get hypoglycemia from depleting glycogen stores.

Front 21

Where is fa-beta-ox regulated? (4 points in cycle)

Back 21

1 malonyl CoA inhibits carnitineacyltransferase 1, 2 NADH inhibits beta-hydroxyacyl CoA dehydrogenase (produces NADH), 3 AcCoA inhibits thiolase (produces AcCoA), 4 respiratory control

Front 22

What is meant by "respiratory control" of fa-beta-ox?

Back 22

dec oxygen inhibits oxphos => decreased oxphos inhibits TCA cycle => inc AcCoA inhibits fa-beta-ox

Front 23

Why do you have to have a supply of carbohydrates in order for fa-beta-ox to continue?

Back 23

to regenerate oxaloacetate so that CAC can keep turning

Front 24

anaplerosis, def

Back 24

replenishing oxaloacetate so that TCA cycle can keep turning

Front 25

Two sources of oxaloacetate?

Back 25

1 generated from pyruvate by enz pyruvate carboxylase, 2 generated from aa carbon skeletons which enter as α-ketoglutarate

Front 26

What is the problem resulting from oxidation of cis-4 f.a.'s? How is this circumvented? (include name of enz that encounters difficulty and 2 enz's that solves the problem)

Back 26

Acyl-CoA dehydrogenase introduces a trans-2 double bond, creating a resonanse-stabilized substrate for enoyl CoA hydratase. Circumvented by 2,4-dienoyl reductase which creates a cis-3 double bond instead, reacted by enz isomerase.

Front 27

What is the problem associated with metabolism of f.a's with an odd number of carbons? How is this circumvented?

Back 27

fa-beta-ox of odd-numbered f.a.'s yields propionyl CoA (=CoA + 3C's). Propionyl CoA (enz propionyl CoA carboxylase, requires biotin)=> (S)-mmCoA (enz methylmalonyl CoA racemase)=> (R)-methylmalonyl CoA (enz methylmalonyl CoA mutase)=> succinyl CoA => citric acid cycle

Front 28

Deficiency of which vitamin will result in an accumulation of methylmalonic acid?

Back 28

Vit B12

Front 29

Name the 3 ketone bodies

Back 29

1 acetoacetate, 2 beta-hydroxybutyrate, 3 acetone

Front 30

CLICKER: Which of these comounds is a ketone body but is not a ketone? 1 pyruvate, 2 lactate, 3 acetoacetate, 4 3-hydroxy-butyrate, 5 acetone

Back 30

Answ: lactate is neither, correct answ is 3-hydroxy-butyrate (3 ketone bodies are: 1 acetoacetate, 2 beta-hydroxybutyrate, 3 acetone)

Front 31

In which organ does most of the acCoA from fa-beta-ox wind up?

Back 31

liver

Front 32

What are the 3 fates of acCoA in the liver?

Back 32

1 oxidation via CAC, 2 synthesis of acetoacetate and beta-hydroxybutyrate (aka ketogenesis of ketone bodies), 3 biosynthesis of cholesterol

Front 33

HMG CoA, acronym

Back 33

hydroxymethylglutaryl CoA

Front 34

CLINICAL APPLICATION: Why do diabetics have fruity-smelling breath?

Back 34

due to acetone produced from ketogenesis

Front 35

What is the effect of carbohydrate deficiency on ketogenesis? Describe the mechanism.

Back 35

INCREASES ketogenesis. Dec glucose => dec anaplerosis => dec slows CAC => acCoA builds up => ketogenesis

Front 36

Effect of ketogenesis on free CoA?

Back 36

increases free CoA, which can then be used in fa-beta-ox

Front 37

What is the fate of acetoacetate after it is produced in the liver?

Back 37

Transported to body tissues (esp heart and brain); converted to acetoacetyl CoA so it can be burned

Front 38

What is a byproduct of converting acetoacetate to acetoacetyl CoA?

Back 38

succinyl CoA is converted to succinate