Metabolism 9 (Exam 4) Flashcards
What are the 3 primary functions of the liver in regard to lipid metabolism?
- Degrade FA into compounds usable for energy
- Synthesize triglycerides (mainly from carbs, some from protein)
- Synthesize other lipids from FA (cholesterol/phospholipids)
What are two examples of situations where energy metabolism leans away from using carbs?
Starvation and Diabetes
In situations where energy metabolism leans away from utilizing carbs, what will happen in the liver?
Large amounts of triglycerides will rapidly appear (mobilization of FA from adipose tissue)
Why is it important to note that some cultures intake less fat?
Where you practice medicine could matter with regards to an animals diet. A pets diet tends to mimic the owners.
Adult dogs need ___ of daily calories from fat.
~5.5%
Adult cats need ___ of daily calories from fat.
~20%
What kind of diet have cats been shown to self select?
High protein (52%) High fat (36%) Low carb (12%)
Most cells can use FA for energy, except for…?
Brain and RBCs
The glycolysis intermediate DHAP can be reduced (reversible reaction) to form what?
Glycerol-3-phosphate
What enzyme is the major link between carb and lipid metabolism?
Glycerol-3-phosphate dehydrogenase
Why can glycerol be immediately placed in the glycolytic pathway?
Why can FA not immediately enter?
Glycerol is immediately changed by intracellular enzymes to glycerol-3-phosphate and this allows it to enter the glycolytic pathway.
FA must be further processed in the mitochondria.
What helps FA enter the mitochondria?
Carnitine shuttle
Which FA have to use the carnitine shuttle to enter the mitochondria?
Long chain FA (> 14 C)
Small and medium chains can pass right through the membranes
Where do we get carnitine from?
It can be derived from the diet or can be biosynthesized from lysine and methionine
What is the second enzyme used in the carnitine shuttle? And what does it do?
CPT1
Allows the Fatty Acyl-carnitine to cross the outer mito membrane.
What is the third enzyme used in the carnitine pathway? What does it do?
CPT2
Breaks Fatty Acyl-Carnitine into Carnitine and Fatty acyl-CoA. By doing so, carnitine is recycled and Fatty acyl-CoA can continue to beta-oxidation
What helps Fatty Acyl-carnitine pass through the inner mito membrane?
Carnitine-Acylcarnitine Translocase (CACT)
This is an antiporter
It also takes carnitine back out of the mitochondria (recycling process)
What is the first enzyme used in the carnitine shuttle? What does it do?
Acyl-CoA Synthetase
This, using ATP, will combine CoA, FA, and carnitine to form = Fatty Acyl-Carnitine
What is beta-oxidation?
It is a catabolic (break down) process occurring in the mitochondria, where FA are used to generate Acetyl-CoA which is able to enter the CAC
During beta-oxidation what is the first step once we have Fatty Acyl-CoA?
The beta carbon of the fatty acyl-CoA binds with oxygen
So, the beta carbon is oxidized
After the beta-carbon of the Fatty Acyl-CoA is oxidized, what will happen?
The acetyl-CoA will split off (enter the CAC), and a new fatty acyl-CoA is formed (but it’s two carbons shorter)
This process will continue until everything is gone
How much ATP is produced from a single beta-oxidation cycle?
Max of 17
5 ATP from H liberated and 12 from a full CAC rotation
In terms of storage how do carbs and fats differ?
Carbs are stored as glycogen and storage is limited (few hundred grams)
But kilograms of fat can be stored in adipose tissue
What happens to excess ingested energy (fat, carbs, or proteins)?
They will be converted to fat due to the amazing storage capabilities of fat
How do carbs and fat differ in terms of energy density?
A gram of fat has 2.5 times the calories of energy for a gram of glycogen
Overall, why is it more beneficial to the body, to store energy in the form of fat?
We can store more fat, and it’s more energy dense
Define Lipodystrophy
Abnormal distribution of fat in the body, the body is unable to maintain/produce healthy fat tissue
If there is an inability to store fat, where is it usually deposited?
In ectopic, or abnormal, sites like the liver, muscle, pancreas and kidney
Absence of fat is associated with what?
Insulin resistance
Hypertriglyceridemia (high blood fat)
NAFLD (Non-alcoholic fatty liver disease)
MetSyn (metabolic syndrome)
What is a common fat related disorder in Galloway calves?
Hepatic lipodystrophy (absence of adipose tissue, leading to lipid accumulation in the liver)
What common fat related disorder is common in pigs?
Adipogenesis (adipocyte hyperplasia)
What common fat related disease is associated with cats?
Hepatic Lipidosis (Feline Fatty Liver)
Define Ketosis. Where does it occur?
Degradation of FA for energy (occurs in the liver)
Define ketone bodies
Ketone bodies are water-soluble molecules that contain the ketone groups produced from fatty acids by the liver. They are readily transported into tissues outside the liver, where they are converted into acetyl-CoA —which then enters the citric acid cycle and is oxidized for energy.
What are the three ketone bodies?
Acetoacetic acid
Beta-hydroxybutyric acid
Acetone
What is crazy about acetoacetic acid and Beta-hydroxybutyric acid?
Their transport is so rapid that their concentration rarely rises above 3 mg/dl, but very large quantities are actually moved due to their high solubility into tissues
What combines with a lack of carb metabolism to create a very high mobilization of FA from tissues?
Low insulin
High glucagon
Increased glucocorticoid production
Why can a limitation of oxaloacetate cause extreme acidosis?
Oxaloacetate is required to bind to acetyl-CoA, so without it, there will be a build up (20x) of acetoacetic acid and Beta-hydroxybutyric acid
What is a cool way that you can diagnose acidosis?
The acetone can be smelled on the breath, as it is “blown off” with exhalation
Why does the keto diet work and not cause major damage to the body?
With a slow change, the body can adapt to use far more acetoacetic acid than usual after a few weeks, even the brain can derive 50-75% of their energy from fats
Who can benefit from keto?
Those with seizures, type 2 diabetes, and of course those wanting to lose weight
What are the components of a phospholipid?
One or more FA, one phosphoric acid radical, and usually a nitrogenous base
What cells form phospholipids?
All cells can form them, but the liver makes 90% of them
The intestinal epithelium also forms quite a few during absorption
What Lecithins or glycerophospholipids did we discuss?
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine
What are lecithins?
Phospholipids that are structural components in the cell membrane that can also have emulsification properties
What are Cephalins?
These are phospholipids that contain the amino acids serine or ethanolamine (like thromboplastin)
What is thromboplastin (a cephalin) used for?
Clotting
What is sphingomyelin?
A phospholipid that usually has a phosphocholine or ceramide and is present in the myelin sheath as an electrical insulator
What is the basic structure of cholesterol?
A sterol nucleus that is synthesized from multiple acetyl-CoAs
How is a basic sterol modified?
Side chains to form cholesterol, cholic acid (basis for bile acids), or many steroid hormones
About 70% of cholesterol in lipoproteins are in the form of ____?
Cholesterol esters
Do we see more endogenous or exogenous cholesterol?
Endogenous cholesterol is formed in cells to a much greater extent than exogenous. Most of the circulating cholesterol was produced by the liver.
Why does ingested cholesterol not change the plasma cholesterol level very much?
Inhibition of essential enzyme for endogenous cholesterol
Why can high saturated fat increase blood cholesterol by 15-25%?
Increased fat deposition in the liver provides increases in acetyl-CoA for production of cholesterol
Why can unsaturated fat depress blood cholesterol?
We are not sure, the mechanism is unknown
Why will a lack of insulin or thyroid hormone increase cholesterol?
Mainly due to changes in the activation of enzymes for metabolism
Why are genetic disorders like an LDL (low-density lipoprotein) receptor mutation so bad?
It prevents the liver from adequately removing cholesterol-rich LDLs from the blood, thus liver has no negative feedback and goes on a rampage of producing cholesterol
What are some diseases associated with dogs that have high cholesterol?
Nephrotic syndrome (bunch of extra stuff in the interstitial space)
Hypothyroidism
Cholestasis (flow of bile slows or stops altogether)
What is a disease associated with cats with high cholesterol?
Cholestasis
What is a major use of cholesterol?
80% is converted to cholic acid for use in bile
What hormones can cholesterol be used to form?
Adrenocortical hormones
Progesterone/estrogen in ovaries
Testosterone in the testes
What use does cholesterol have in the skin?
It’s resistant to water-soluble substances and chemical agents, prevents water evaporation
What is the most important use of cholesterol?
Structural components of cell membranes
What is atherosclerosis?
It is a disease of middle to large size arteries, where plaques form on the inside surfaces of arterial walls
What is arteriosclerosis?
Thickened or stiffened blood vessels of all size
What is the general pathway for Atherosclerosis?
- Damage occurs to vascular endothelium
- Adhesion molecules attach
- Monocytes and lipids will accumulate (mostly LDLs)
- Monocytes will enter the intima, differentiate to macrophages, and oxidize lipoproteins (now a foam cell)
- Macrophage foam cells aggregate and cause a fat streak
- Continued fatty growth bulges into the artery and reduces blood flow
Why can atherosclerosis become deadly?
The fatty growths can rupture or cause blood clots to form
50% of all U.S. and Europe deaths are from ____.
Vascular disease
What type of animals can get atherosclerosis?
Herbivores:
- Dogs, cats, tigers, lions eat a lot of saturated fat and don’t get plaque buildup (unless the thyroid is removed)
- Rabbits, mice, guinea pigs, opossums and nonhuman primates all are models of athero
When FA are mobilized out of the adipose tissue, where are they deposited? Why?
Liver, this is where they are broken down
What are the components or products of triglyceride break down?
FA and glycerol
What transports long-chain FA into the mitochondria for beta-oxidation?
Carnitine Shuttle
Is beta-oxidation an effective means of generating ATP? What type is best?
Yes. Longer chain FA are best because they produce more ATP
In the event of low carbs, the liver generates excess acetyl-CoA. What happens?
Production of acetoacetic acid, beta-hydroxybutyric acid and acetone (ketosis)
Outside of the cell membrane composition, what is cholesterol converted to?
Cholic acid for use in bile
Which type of animal is predisposed to developing atherosclerosis?
Herbivores
