nuclear hormone receptors which bind directly to hormones which diffuse into the nucleus, then change conformation and initiate transcription.
Saturated fatty acids can bind to some PPARs and thereby increase the expression of genes involved in. . .
Saturated fatty acids can bind to some PPARs and thereby increase the expression of genes involved in cholesterol and fat synthesis.
Unsaturated fatty acids can bind to some PPARs and thereby increase the expression of genes involved in. . .
breakdown of fat and repression of fat and cholesterol synthesis.
Diets that include high amounts of ___ and ___ may promote fat synthesis
Diets that include high amounts of saturated and trans fats may promote fat synthesis, which can lead to insulin resistance and cardiovascular disease.
The rate-limiting step of fatty acid synthesis
The fatty acids produced in lipogenesis will be packaged into triglycerides and exported from the liver in the form of ___.
The fatty acids produced in lipogenesis will be packaged into triglycerides and exported from the liver in the form of VLDL.
β-oxidation provides. . .
______ are more atherogenic (lead to formarmation of plaques in arteries) than cholesterol itself.
Saturated fats and trans fats are more atherogenic (lead to formarmation of plaques in arteries) than cholesterol itself.
Palmitate and Stearate
"Essential" fatty acids
Linoleic acid and α-linolenic acid
Humans do not have the machinery to introduce ____ into oleic acid.
Humans do not have the machinery to introduce the second double bond into oleic acid.
We therefore need to get polyunsaturated fats in the diet.
Important α-linolenic acid derivatives
EPA and DHA
In the fed state, excess glucose is. . .
. . . converted into fat by the liver and sent to adipose tissue for storage.
Acetyl-CoA traverses the mitochondrial membrane in the form of. . .
For efficient synthesis of fatty acids from glucose, ____ are required.
For efficient synthesis of fatty acids from glucose, mitochondria are required.
This is for two reasons: 1. PDH is only present in the mitochondrial matrix, and 2. the main source of Acetyl-CoA for fatty acid synthesis comes from citrate which traverses the mitochondrial membrane.
Acetyl-CoA Carboxylase mechanism
Malonyl CoA inhibits. . .
This ensures that lipogenesis and lipolysis are not occuring simultaneously.
Regulation of Acetyl-CoA Carboxylase
Fatty acid biosynthesis mechanism
Reaction catalyzed by hormone sensitive lipase
Hydrolysis of the first of the three acyl chains on a triacylglyceride, producing one fatty acid and a diacylglyceride.
Hormone sensitive lipase regulation
Protein on the adipocyte lipid droplet membrane which, when activated by glucagon -> PKA phosphorylation, enables hormone sensitive lipase to access lipid droplets.
Charging of fatty acids prior to the beginning of β-oxidation
Rate limiting step for β-oxidation
Movement of fatty acids to the mitochondrial matrix
Regulatory role of malonyl CoA
Comparing products of glucose and fatty acid metabolism
Why couldn't you just run the cell on β-oxidation without ever using the TCA cycle or PDH?
Lack of enough CoA
However, this can be partially overcome in times of excessive β oxidation by using fatty acids to make ketone bodies.
After a one to two day fast, ____ begins to accumulate in the liver greater than the level that is needed to meet energy needs.
After a one to two day fast, acetyl-CoA begins to accumulate in the liver greater than the level that is needed to meet energy needs.
This is what triggers ketogenesis
Context of ketogenesis
Circulating ketone bodies are important for maintaining ____ during periods of starvation.
Circulating ketone bodies are important for maintaining muscle mass during periods of starvation.
They reduce the demand on amino acids for carbon skeletons, allowing muscle to avoid degradation for brain fuel.
Ketone body biosynthesis
Takes place in the mitochondrial matrix
____ is shared by both the ketone body biosynthetic pathway and the steroid biosynthetic pathway.
HMG-CoA Synthase is shared by both the ketone body biosynthetic pathway and the steroid biosynthetic pathway.
Ketone bodies are _____ and can be thought of as _____ forms of fatty acids.
Ketone bodies are hydrophilic and can be thought of as water-soluble forms of fatty acids.
Ketone body utilization
Only cells expressing ____ may harness ketone bodies as an energy source.
Only cells expressing thiophorase may harness ketone bodies as an energy source.
Propionyl CoA metabolism
Major steps in propionyl CoA metabolism
1. Carboxylation by propionyl-CoA carboxylase and biotin
2. Enantiomerization by methylmalonyl-CoA racemase
3. Reorganization to succinyl-CoA by methylmalonyl-CoA mutase and cobalamine
4. Conversion to malate via the TCA cycle
5. Oxidative decarboxylation to pyruvate and CO2 by malic enzyme, also producing NADPH