Metabolism: Fundamentals Flashcards
what is metabolism?
Balance of the body and body processes
Sum of all enzyme catalyzed reactions
what is metabolites?
Small molecules involved in metabolism
Synthesis or degradation
Two carbon acetyl group is the central intermediate for rxns that use ATP
this is the definition for the following:
Balance of the body and body processes
Sum of all enzyme catalyzed reactions
metabolism
this is the definitio for the following:
Small molecules involved in metabolism
Synthesis or degradation
Two carbon acetyl group is the central intermediate for rxns that use ATP
metabolites
what is a brief definition for the metabolic pathway?
Regulates the flow of metabolites
Product of one reaction is the starting material/ substrate for another reaction
what is flux?
movement from one step to another
what are the dietary fuel molecules?
carbs, fats, proteins/amino acids
where do carbs, fats, proteins/amino acids come from? the caloric content?
Carbohydrates (4kcal/g)
Sugars, anything ending in -ose (glucose)
Protein (4kcal/g)
Comes from amino acids
Alcohol (7kcal/g)
ethanols
Fats (9kcal/g)
Fatty acids, triglycerides, lipids
what is catabolism?
The breakdown of biomolecules to produce energy (via oxidation) and the building blocks for other synthesis. Fuels are oxidized completely to CO2 and H2O.
where do the products of catabolism end up?
they eventually end up in the TCA cycle
Example: fuel oxidative pathways, glycolysis
Releases energy (ATP, GTP, NADH) or nucleoside triphosphate, reduced coenzymes, acetyl coenzyme A
what are examples of nucleoside triphosphate?
(e.g., ATP, GTP)
what are examples of reduced coenzymes?
(NADH, NADPH, FADH2, FMNH2)
what is anabolism?
The biosynthesis of more complex molecules from small precursors in reductive (i.e., uses energy) pathways.
T/F, anabolic pathways are divergent?
T, Anabolic pathways are divergent starting with a few metabolites and producing many different molecules
how can we best compare catabolism and anabolism?
catabolism uses glycolysis
anabolism uses gluconeogenesis
what does anaerobic mean?
Pathways that operate and, more specifically, lead to ATP production, in the absence of oxygen (O2).
Example: Glycolysis – major carb pathway
ATP production independent of O2
what does aerobic mean?
Pathways that require O2 to operate and, more specifically, lead to ATP production.
Example: Oxidative Phosphorylation
O2 mandatory
what are both aerobic and anaerobic metabolism interdependent on?
in humans
Beta-oxidation of fatty acids – major fat pathway
Amino acid oxidation – major AA pathway
what is the significance of Glycolysis, FA oxidation and AA oxidation? what is the importance of the product?
all produce NADH, which carries electrons to the Electron Transport Chain; the product helps to fuel metabolism and O2 is absolutely essential, ATP is produced
what happens if oxygen is not present? what about if ischemia happens?
ETC shuts down, NADH levels rise rapidly. Glycolysis inhibited. So is fatty acid oxidation, AA oxidation and the TCA cycle.
Ischemia? Glycolysis kicks in to produce ATP as long as it can. Anaerobic ATP production.
what are the importance of metabolic pathways, like the TCA cycle?
Metabolic pathways are designed to meet specific cellular needs.
They can be the source of metabolites needed by other pathways
amino acid synthesis
gluconeogenesis
fatty acid synthesis
amino acid synthesis
heme synthesis, this is called efflux and dependent on level of activity
Cellular metabolites can reenter the pathway as needed for it to function
Compare and contrast “substrate cycles” versus futile cycling in metabolic pathways, using glycolysis and gluconeogenesis as examples. Include a consideration of reciprocal regulation of key enzymes in metabolic pathways. This may be hard from just the introduction level, but it will become clearer during the later lectures in this group.
Substrate cycles
cycles that use the same pathway for the exact opposite function
Example is glycolysis and gluconeogenesis are the same pathway but the arrows are different directions. The product of glycolysis is the beginning material for gluconeogenesis.
Reciprocal regulation
Controlled by separate regulatory enzymes
When one is “on” the other is “off”
Futile cycling
Burning up energy reserves in cyclical reactions
what is substrate cycles?
cycles that use the same pathway for the exact opposite function
Example is glycolysis and gluconeogenesis are the same pathway but the arrows are different directions. The product of glycolysis is the beginning material for gluconeogenesis.
what is reciprocal regulation?
Controlled by separate regulatory enzymes
When one is “on” the other is “off”
what is futile cycling?
Burning up energy reserves in cyclical reactions
fatty acid oxidation as an example, relate how compartmentalization of metabolic pathways allows for efficient regulation of the metabolic pathways. Very generally at this level – see the Fatty Acid Oxidation lecture for a more complete explanation.
Compartmentalization
Restricting pathways to particular sub-cellular organelles
Liver cells: mitochondria imports fatty acids for oxidation and the ER dephosphorylates glucose-6-phosphate to export glucose
Liver can:
Oxidize fats for energy and synthesize fats for storage
Use glucose for energy or synthesize glucose to be released
what is the Fed state?
Fed state:
● Eat glucose and goes into the blood → release of insulin to break it down
● Now cells want to suck up that glucose (all tissues= glucose is the universal energy source)
● Increase glucose= increase insulin= decrease glucagon
● Glucose broken down by the liver and is used by the brain, RBC, muscle, and adipose tissues
what is the Fasting state?
● No glucose coming in from the diet
● Decrease glucose= decrease insulin= increase glucagon
● Resting CBS is 70-100 (not enough blood glucose to signal insulin)
● Main customers of the remaining glucose is the brain and the RBC
● The muscle and the heart will use ketone bodies as their energy source (other than fast-twitch muscle)
● Liver: maintains blood glucose levels
● FAs from adipocytes provides major source of energy
● Liver glycogen stores start to run down (18-24 hours)
What is the long starved state?
● Muscle starts to get scared and keeps its AAs for itself
● Brain has to use ketone bodies as its main source of energy (to make acetyl CoA)
● RBCs keep getting glucose from the little bit created by the liver because it can’t use ketone bodies
● Muscle uses FA oxidation as primary energy source
● Less AA being used for gluconeogenesis= less nitrogen so decreased urea produced
Define the major role of insulin and glucagon for metabolism, and include how the blood glucose level controls which of these hormones is dominant.
Insulin
● used to break down glucose in the fed state
● Signals cells to grow, build, and store excess fuels
Glucagon
● the energy storage
● Signals the fasting state: utilize stored fuels for energy
Identify the tissues that utilize glucose after a carbohydrate meal.
Brain, muscle, RBC, liver, adipose
Identify the tissues that utilize fats and amino acids after a meal.
Tissues, adipose, liver
Identify the tissues where the body stores carbohydrate, fat and protein.
Fats
● Stored in adipose tissue as triglyceride
● 9 kcal/gm utilized
Glycogen
● Glucose storage in liver, muscles, etc
● 4 kcal/gm utilized
Protein
● Skeletal muscle can provide amino acids on a short-term basis
● 4 kcal/gm utilized
Recognize how fasting affects fat storage/utilization in adipose tissue and glucose utilization/storage in the liver.
● Have to bring fuel out from stores for use
● Uses these fuel stores for energy in tissues, especially the brain
During a long fast, relate key changes in metabolite production and utilization (i.e., ketone bodies) and the specific processes that occur in different tissues (esp. muscle, liver, brain) Again, do this at the level of having the picture in front of you and you can answer questions about the flow of molecules.
● Adipose tissue is going to release TG as glycerol and FA in order to help fuel the liver
● The liver’s ability to make glucose via gluconeogenesis has gone down significantly
● The glucose that is left being produced by the liver is used in the RBCs
● FAs are used to make acetyl-CoA into ketone bodies → main fuel for the brain
● FAs are used to fuel the muscles
● Less AA used for gluconeogenesis= less urea being produced
what are normal blood glucose levels?
80-100 mg/dL
when do blood glucose levels rise and peak? after two hours of eating?
about an hour after eating, insulin rises with glucose; the blood glucose level is back to the basal range (80-100 mg/dL)
what state is the body in after twelve hours of eating?
the body is in the basal (or post absorptive) state
Glucagon to insulin ratio is high
Serum insulin levels are low
after twelve hours of eating, what is happening to glycogen stores?
are starting to running down (18-24 hour supply)
after twelve hours of eating, how long does it take for glycogen stores to run down?
(18-24 hour supply)
after twelve hours of eating, what process supplies blood glucose?
gluconeogenesis (glucose synthesis from lactate, glycerol and/or alanine)
after twelve hours of eating, what happens to FA?
oxidized to yield energy in many tissues (muscle, liver) to preserve glucose in blood for tissues that really need it.
what is the major source of fuel during fasting?
Triglyceride (TG)
FA oxidized (β-oxidation) to acetyl CoA which leads to lots of ATP production Glycerol backbone used for gluconeogenesis
what is the role of the liver during fasting?
most FA taken up used to produce ketone bodies, which are used by some tissues (muscle and kidney, and if fasting lasts 2 or more days, brain also)
Ketone bodies converted to acetyl CoA and then to CO2 and H2O with the production of ATP
during a short fast, what is the liver doing?
maintains blood glucose levels
during a short fast, how are FAs used?
provide major source of energy
during a short fast, what is the importance of ketone bodies?
an important source of energy for many tissues
during a short fast, what is the status of the brain?
Brain continues to rely on blood glucose primarily
glycogen breakdown and gluconeogenesis by liver
Gluconeogenesis driven mainly by amino acids donated from the amino acid pools stored in muscle
during a short fast, what is the by product of utilizing amino acids for gluconeogenesis?
nitrogen, which is converted to urea by urea cycle
