fatty acid oxidation & ketones

Question 1

how long can we sustain energy levels using glycogen

Answer 1

12 hours

Question 2

how long can we sustain energy levels for using lipid energy reserves

Answer 2

Up to 12 weeks

Question 3

when is protein used for energy

Answer 3

when muscle glycogen stores fail

Question 4

what is the structure of a fatty acid

Answer 4

carboxylic head group with aliphatic tail
saturated and unsaturated
most are derived from triglycerides and phospholipids

Question 5

where are fatty acids activated

Answer 5

in the cytoplasm

Question 6

where are fatty acids oxidised

Answer 6

in the mitochondria

Question 7

what is the process for activating fatty acids

Answer 7

Fatty acid + ATP + CoA > Acyl-CoA + PPi (pyrophosphate) + AMP.

The adenosine is taken from ATP and used to make the Acyl-Coenzyme A (Acyl-CoA).

Question 8

what happens if the Acyl-CoA has less than 12 carbons

Answer 8

it can diffuse through mitochondrial membranes

Question 9

what happens if the Acyl-CoA has more than 14 carbons

Answer 9

it is taken through the mitochondrial membrane using the carnitine shuttle

Question 10

why is fatty acid oxidation called beta oxidation

Answer 10

because it occurs through the sequential removal of 2-carbon units by oxidation at the beta-carbon position of the fatty Acyl-CoA molecule.

Question 11

what does each round of beta oxidation produce

Answer 11

1 mol of NADH, 1 mol of FADH2 & 1 mol of Acetyl CoA.

Question 12

what happens to the acteyl CoA made from beta oxidation

Answer 12

used in the Krebs cycle to produce glucose

a small proportion of it is converted to ketones

Question 13

what happens to the NADH and FADH2 produced from beta-oxidation

Answer 13

used in oxidative phosphorylation

Question 14

why can fatty acids not act as a fuel source for the nervous system

Answer 14

because fatty acids cannot get through the blood brain barrier

Question 15

compare the yield of energy production from fatty acid oxidation and carbohydrate oxidation

Answer 15

fatty acid oxidation yields far more energy than carbohydrate oxidation

The net result of the oxidation of one mole of oleic acid (an 18-carbon fatty acid) will be 146 moles of ATP as compared to 38 moles of ATP produced from 1 mol of glucose

Question 16

describe process of fatty acid (beta) oxidation

Answer 16

Oxidation of fatty acids occurs in the mitochondria, however most fatty acids (that are over 12 carbons long) cannot get through the outer-mitochondrial membrane on their own.

• In order to get through, the Acyl CoA must be converted: Acyl CoA > (enzyme Carnitine acyltransferase 1 (resides in the outer mitochondrial membrane))> Acyl Carnitine. In this process the Coenzyme A is removed from Acyl CoA and is recycled, as you can see, the molecule Carnitine is added. The Acyl Carnitine can then be transported into the mitochondria through the outer mitochondrial membrane.
• Once inside the mitochondria another enzyme Carnitine acyltransferase 2 converts Acyl carnitine back to Acyl CoA : Acyl Carnitine > (enzyme Carnitine acyltransferase 2) > Acyl CoA. In this process a Coenzyme A is re-added and the carnitine ripped off to regenerate Acyl CoA. The carnitine can then diffuse through the outer mitochondrial membrane to be used again to covert Acyl CoA to Acyl Carnitine (THIS IS KNOWN AS THE CARNITINE SHUTTLE)
• Now the fatty Acyl CoA can be oxidised.

Question 17

what are ketones

Answer 17

molecules produced by the liver from acetyl CoA

have a characteristic fruity/nail polish remover-like smell

Question 18

why does ketogenesis occur

Answer 18

During high rates of fatty acids oxidation, primarily in the liver, large amounts of acetyl-CoA are generated. These exceed the capacity of the Kreb’s/TCA cycle, and one result is the synthesis of ketone bodies - known as ketogenesis

Question 19

where does ketogenesis occur

Answer 19

in the mitochondrial matrix of liver cells

Question 20

give 3 examples of ketone bodies

Answer 20

acetone
acetoacetate
B-hydroxybutyrate

Question 21

outline process of ketogenesis

Answer 21

2 Acetyl CoA ’s are converted by the enzyme thiolase (used in b-oxidation), back to Acetoacetyl CoA. Under the action of two further enzymes the Acetoacetyl CoA can be converted to Acetoacetate, acetoacetate can then enter the blood or it can be converted to b-hydroxybutyrate under the action of another enzyme, which can then enter the blood. When the level of glycogen in the liver is high the production of b-hydroxybutyrate increases. Another fate of the acetoacetate is that it can spontaneously be converted to acetone. Since acetone is volatile it is rapidly expired by the lungs

Acetoacetate & b-hydroxybutyrate can both be oxidised as fuels in most tissues, including skeletal muscle (see diagram). Cells transport the acetoacetate and b-hydroxybutyrate from the blood into the cytosol then into the mitochondrial matrix. Here b-hydroxybutyrate is oxidised back to acetoacetate.

Acetoacetate can then be activated to Acetoacetyl CoA which can then be cleaved into two molecules of Acetyl CoA by the thiolase enzyme (same enzyme involved in b-oxidation). Then the Acetyl CoA can be used in the Kreb’s cycle to produce ATP

Question 22

what effect does low carbohydrate utilisation have on ketogenesis

Answer 22

the level of oxaloacetate will also be low resulting in a reduced flux through the Kreb’s cycle - leading to an increased release of ketone bodies from the liver to be used as fuel by other tissues

Question 23

why can ketone bodies not be used as a fuel

Answer 23

because the liver does not have enough of the enzyme succinyl coA: acetoacetate coA (theenzyme used to convert acetoacetate to acetoacetyl CoA)

so ketone bodies cant be converted to acetyl CoA in the liver this ensure that extrahepatic tissues have access to ketone bodies as a fuel source during prolonged starvation

Question 24

what happens in the early stages of starvation

Answer 24

the last remnants of fat are oxidised, the heart and skeletal muscle will consume primarily ketone bodies in order to PRESERVE GLUCOSE FOR USE BY THE BRAIN - when glucose in the brain decreases then the brain CAN use ketone bodies for energy

Question 25

what 4 factors are involved in the regulation of ketogenesis

Answer 25

Control in the release of free fatty acids from adipose tissue directly affects the
level of ketogenesis in the liver

high concentration of glycerol 3 phosphate in liver –> triglyceride production

low level of glycerol 3 phosphate in liver –> increased ketone body production

Question 26

what does fat oxidation depend on

Answer 26

the amount of glucagon (activation) or insulin (inhibition) present

Question 27

what is rate of ketone production like during normal physiological conditions

Answer 27

production of ketone bodies occurs at a relatively slow rate during normal feeding
and under normal physiological status

Question 28

what effect do carbohydrate shortages have on ketone body production

Answer 28

they cause the liver to increase the production of ketone bodies from the acetyl-CoA generated from fatty acid oxidation. This allows the heart and skeletal muscles primarily to use ketone bodies for energy, thereby preserving the limited glucose for use by the brain

Question 29

what causes the most significant disruption in the level of ketosis

Answer 29

untreated insulin-dependent diabetes mellitus

Question 30

what is ketoacidosis

Answer 30

occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement

Question 31

when is ketoacidosis often seen

Answer 31

in newly diagnosed type 1 diabetics

also occurs in chronic alcohol abuse

Question 32

what are the symptoms of ketoacidosis

Answer 32

hyperventilation and vomiting

Question 33

how does diabetic ketoacidosis occur

Answer 33

it results from a reduced supply of glucose
(since there will be a significant decline in circulating insulin) and an increase in fatty acid oxidation (due to an increase in circulating glucagon). The increased production of Acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them. Ketone bodies are relatively strong acids (pH 3.5), and their increase lowers the pH of blood. This acidification of the blood can have many consequences but most critical is the fact that it IMPAIRS THE ABILITY OF HAEMOGLOBIN TO BIND TO OXYGEN - note if a patient is in diabetic ketoacidosis, the excess ketones in the blood will result in their BREATH SMELLING OF PEAR DROPS (KETONES).

Question 34

what are the consequences of ketoacidosis

Answer 34

ketones are relatively strong acids
excessive ketones lower the pH of the blood
this impairs the ability of haemoglobin to bind to oxygen