Metabolism Flashcards
Liver Storage
LIVER IS IMPORTNANT FOR METABOLISM
-storing glucose, etc. for the rest of the body to keep it fueled and in homeostasis
3 most important molecules in metabolism
- glucose 6-P
- Pyruvate
- Acetyl Co-A
- 30 or 32 ATP made from 1 glucose molecule
- Much of the metabolic rxn and generation of ATP occurs in the mitochondria:
- Krebbs Cycle (using Acetyl CoA)
- oxidative part (electron transport chain using potential energy): electrons are given to oxygen to form water
- Phosphorylation part
- Want about 70% in triphosphate form for ATP
- ATP lasts about 5 seconds, so need to be constantly making ATP
- how are we using all this ATP? Major consumer is pumping sodium/potassium exchange for cell membrane potential changes
Energy Producing Parts of Glycolysis
- blood glucose to glucose 6-P
- 2 phsophoenolpyruvate (PEP) to 2 pyruvate
- Rate limiting step (essentially irreversible): phosphofructokinase (PFK)
- increase in ATP, citrate, H+ will inhibit pathway
- increase in AMP will stimulate pathway
- PFK is the rate controlling step, regulated allosterically.
- Glycolysis needs to be controlled for example when gluconeogenesis is occurring
Gluconeogenesis
- Happens in Liver!
- Process of making glucose 6-P from 2 pyruvate (which becomes blood glucose)
- metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids
- Depression of glycolysis in liver is due to that it is meant to be providing glucose to the rest of the body and not metabolizing it itself
- Insulin upregulates glycolysis to then make some gly
2 ADP —-> ATP + AMP
- enzyme is adenylate kinase
- This is done to create AMP to signal cell that there is not enough energy, need to make more!
- also makes more ATP in process in the mean time
- AMP usually only needed when more energy is required
When does glycolysis operate?
- Most of the time in most tissues
Glycogen
- stored in the liver and muscles if there is excess glucose
- glycogenesis is signaled by insulin (uses E)
- glycogenolysis is signaled by glucagon ( or epinephrine in liver) –> produces E
Acetyl CoA
- main component of Krebbs cycle output
- Used for fatty acid synthesis (E using)
- Or created by B-oxidation of fatty acids for triglycerides (adipose tissue)
- If body starts to run out of insulin could get ketoacidosis
- Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids
- Can smell acetone on their breath
- Ketone bodies: Acetoacetate, β-Hydroxy butyrate and Acetone
- Ketone bodies are produced from acetyl-CoA, mainly in the mitochondrial matrix of liver cells when carbohydrates are so scarce that energy must be obtained from breaking down of fatty acids
nefa’s
- non esterified fatty acids
- Nefa’s (non-esterified fatty acids): fatty acids released from stores
- To be used as energy when glucose levels are low (fasting)
Fasting Response
- FASTING RESPONSE:
1. Glucose from energy store in liver (glycogen stores)
2. Energy from aa’s (muscle) as skeletons for glucose (converted to pyruvate)
3. Energy from Fatty Acids (nefa) from adipose tissues - Using OAA (and ATP) to make glucose from pyruvate and acetyl coA , still increasing Acetyl CoA levels and therefore will make short chain fatty acids (acetoacetate) in the liver which will make ketone bodies, healthy to a certain point,
but then can be very dangerous –> ketogenesis
Ketoacidosis
- Ketone Bodies can get through the BBB and act as fuel for brain in short fasting
- OAA will decrease and Acetyl CoA will promote gluconeogenesis. Likely to use oAA to make glucose than ATP. Glucose will not feedback in this tissue (liver) as the glucose is being used in OTHER tissues
- If there is a lot of fat in the liver you can get “fatty liver”, will be making acetyl CoA and liver doesn’t want it so it makes ketone bodies
- In extreme fasting, a lot of ATP being made from adipose tissue, do not need CAC
–> natural default pathway would be the formation of ketone bodies
- Ketoacidosis: so many ketone bodies present that the pH of the blood changes
Fed State
Fed state: LOTS OF GLUCOSE
- Store as glycogen
- As use! Mainly FA synthesis to be made and stored elsewhere
- Can be taken up into muscles as well
- Carnivores are not as insulin dependent as they can use aa’s to make pyruvate from their protein diet
- Aa’s from diet… glucagenic ones would go through gluconeogenesis to make glucose and the acetyl CoA ones would go to FA synthesis
- In the fed state: glucose is used by the brain for fuel
Hindgut Fermentation
(Horse, Rabbit)
- Fermentation is an ADD ON: anaerobic process to feed themselves.
- Advantage is that it is an energy source for the animal using it. Break down to release glucose and that is fermented (undergoes glycolysis in microbes themselves). Key that there is no oxygen so they can produce volatile fatty acids that they can then oxidize
- VA’s absorbed in large intestine
- Host gets AEROBIC process ocurring from anaerobic
- Can’t really do any post fermentation digestion
- microbes are excreted rather than used as metabolites
- Rabbit: eats its dropping (caecotrophs) and then can take microbes that way
–> post fermentation digestion. Rabbits do both, get both advantages
- Buturate (4 chain FA) and propuronic acid, acetate –> volatile FA
- acetate–> add a CoA –> acetyl CoA
Propanate–> this is turned into OAA–> make into glucose
Buturate–> acetyl CoA
Foregut Fementer
(ruminants)
- Do not get glucose source from diets because it is always fermented first
- Volatile FA’s become main source of metabolism (absorbed over the rumen)
- Deficient in glucose and aa’s as a result
- Microbes will be broken down as a protein source though in this fermentation tank
- Can then be absorbed in the intestine
- To get more protein: give soy bean. Rumen bypass protein which is protected
From rumen and the aa’s are released into the rumen to be a gluconeogenic substrate
Ruminant Pregnancy and Fermentation
Ruminants: need glucose MORE (metabolically challenged) during lactation and pregnancy!
Trouble–> not much glucose and overloads ability
To produce glucose–> reproduction disease. Reaction would be going into starvation mode and make ketone bodies. Bovine ketosis–> due to lactation. Fetuses over placenta and cow becomes hypoglycemic because glucose is going to fetus rather than other parts of body–> (pregnancy toxemia). Overcome by giving gluconeogenic substrates, change diet to get more propranate (this is turned into OAA to make more glucose)
-prodcution diseases make ketone body production excessive
Allosteric binding
Hb is an example!
Stimulated by allosteric binding and will take on more oxygens in a certain state!
Binding of one O2 molecule allows for more to bind!
Reversible Covalent Modification
- Think Insulin and Glucagon
