fatty acid oxidation & ketones Flashcards
how long can we sustain energy levels using glycogen
12 hours
how long can we sustain energy levels for using lipid energy reserves
Up to 12 weeks
when is protein used for energy
when muscle glycogen stores fail
what is the structure of a fatty acid
carboxylic head group with aliphatic tail
saturated and unsaturated
most are derived from triglycerides and phospholipids
where are fatty acids activated
in the cytoplasm
where are fatty acids oxidised
in the mitochondria
what is the process for activating fatty acids
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).
what happens if the Acyl-CoA has less than 12 carbons
it can diffuse through mitochondrial membranes
what happens if the Acyl-CoA has more than 14 carbons
it is taken through the mitochondrial membrane using the carnitine shuttle
why is fatty acid oxidation called beta oxidation
because it occurs through the sequential removal of 2-carbon units by oxidation at the beta-carbon position of the fatty Acyl-CoA molecule.
what does each round of beta oxidation produce
1 mol of NADH, 1 mol of FADH2 & 1 mol of Acetyl CoA.
what happens to the acteyl CoA made from beta oxidation
used in the Krebs cycle to produce glucose
a small proportion of it is converted to ketones
what happens to the NADH and FADH2 produced from beta-oxidation
used in oxidative phosphorylation
why can fatty acids not act as a fuel source for the nervous system
because fatty acids cannot get through the blood brain barrier
compare the yield of energy production from fatty acid oxidation and carbohydrate oxidation
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
describe process of fatty acid (beta) oxidation
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.
what are ketones
molecules produced by the liver from acetyl CoA
have a characteristic fruity/nail polish remover-like smell
why does ketogenesis occur
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
where does ketogenesis occur
in the mitochondrial matrix of liver cells
give 3 examples of ketone bodies
acetone
acetoacetate
B-hydroxybutyrate
outline process of ketogenesis
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
what effect does low carbohydrate utilisation have on ketogenesis
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
why can ketone bodies not be used as a fuel
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
what happens in the early stages of starvation
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
what 4 factors are involved in the regulation of ketogenesis
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
what does fat oxidation depend on
the amount of glucagon (activation) or insulin (inhibition) present
what is rate of ketone production like during normal physiological conditions
production of ketone bodies occurs at a relatively slow rate during normal feeding
and under normal physiological status
what effect do carbohydrate shortages have on ketone body production
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
what causes the most significant disruption in the level of ketosis
untreated insulin-dependent diabetes mellitus
what is ketoacidosis
occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement
when is ketoacidosis often seen
in newly diagnosed type 1 diabetics
also occurs in chronic alcohol abuse
what are the symptoms of ketoacidosis
hyperventilation and vomiting
how does diabetic ketoacidosis occur
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).
what are the consequences of ketoacidosis
ketones are relatively strong acids
excessive ketones lower the pH of the blood
this impairs the ability of haemoglobin to bind to oxygen
