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Key themes
One: All cells need a constant supply of ATP
Two: Blood glucose levels must remain relatively constant
Three: Must spare body protein
Four: Metabolic flexibility
Randle cycle
The use of one macronutrient inhibits the use of another
Fatty acid oxidation inhibits
pyruvate dehydrogenase
Requirements for Survival
One: Must synthesize compounds that are not found in diet
Two: Protect from toxins and changing environments
How to meet requirements for survival
One: Fuel oxidation pathways
Two: Fuel storage and mobilization
Three: biosynthesis
Four: Detoxification and waste disposal
Mechanism for Fuel → Reduced Co enzyme
Oxidation
Mechanism for reduced coenzyme → ATP
ETC
Fuel oxidation pathways require
oxygen
In the fed state, excess fuels go to
storage
In the fasted state, fuel storage is
oxidized and becomes ATP
Adipose fuel storage
TAG
Muscle and liver fuel storage
glycogen
Energy Requirements are a cumulation of
basic functions and physical activity
ATP cycle
ATP → Energy utilization → ADP → energy production → ATP
Energy production in ATP cycle
macronutrients, O2 make ATP and release water and heat
Energy utilization in ATP cycle
uses one Pi from ATP and is used to support body functions
Ways ATP is used
Sodium potassium pumps
biosynthesis
detoxification
muscle contraction
thermogenesis
As concentration of ADP increases…
oxidation of fuels increases
Major carbohydrates
starch, sucrose, lactose, fructose, glucose
Proteins are a source of
nitrogen
There are ____ essential amino acids
9
Triglycerides are made of
a glycerol and three fatty acids
Triglycerides are a good form of fuel storage because
they have high energy with a low weight burden
Fat utilization in liver
gluconeogenesis
Storage of glycogen
liver and msucle
Glycogen storage in the muscles is used for
energy during exercise
Glycogen storage in liver is used for
maintaining blood glucose
Daily expenditure
One: Basal metabolic rate
Two: Physical activity
Three: thermic effect of food
Factors that may effeect resting metabolic rate
gender, age, body temperature, environmental temperature, thyroid status, pregnancy
Fatty acid requirements
omega 3 and omega 6 (alpha linoleic)
Protein requirements
0.8 gram per day/ kg of body weight
Positive nitrogen balance
nitrogen in is higher than nitrogen out
Stage where nitrogen balance is positive
childhood, growth, pregnancy
Stage where nitrogen balance is zero
healthy adult
Nitrogen balance
Nitrogen in and nitrogen out are equal
Stage where nitrogen balance is negative
Nutrient deficiency, catabolic stress
Negative nitrogen balance
Nitrogen in is less than nitrogen out
What occurs during the fed state
digestion and absorption
Fate of glucose in fed state
One: Ox for energy
Two: Used to synthesize other compounds
Three: Stored as glycogen or TAG
Fate of amino acids in fed state
One: Energy source
Two: Protein synthesis
Three” Synthesis of nitrogen containing compounds
Fate of fats in fed state
One: Stored as TAG
Two: Synthesize membrane lipids
Three: oxidized for energy
Carbohydrates are absorbed as
monosaccharides
Carbohydrates go directly to
the blood stream
Major enzyme for breaking down carbohydrates
pancreatic amylase
Raising insulin lowers
glucagon
Fate of glucose in the liver (fed)
One: stored as liver glycogen
Two: used in glycolysis
Three: Converted to triglycerides for energy
Glucose to the brain (fed)
Oxidized for energy
Glucose in RBC (fed)
Oxidized for energy anaerobically
Glucose in muscles (fed)
One: oxidized for energy
Two: Stored as muscle glycogen
All tissues take up glucose in the
fed state
Fate of fat in the fed state
One: Triglycerides in the SI are broken down by pancreatic lipase and absorbed and transported via chylomicrons
Two: Fatty acids go to adipose tissue where glycerol from the liver comes to make triglycerides to be stored in adipose tissue
Three: glycerol returns to liver
VLDL
Carries fats away from the liver (fats produced by the body) and cholesterol
Fate of proteins in liver (fed)
TCA cycle
Synthesize nitrogen containing compounds
Flush out in the urea cycle
Proteins are broken down to enter the
free amino acid pool
Uses of amino acids
synthesize nitrogen containing compounds and other
Ways amino acid pool is replenished
Diet
Body proteins
Goals of the fasted state
maintain ATP
maintain blood glucose
maintain metabolic flexibility `
Blood glucose peaks ___ hour after eating
One
After ___ hours, blood glucose returns to normal
two
Short term fast time
8-12 hours
Liver is critical to maintaining
blood glucose
How liver maintains blood glucose
Degrades liver glycogen
Gluconeogenesis
Ketone body synthesis maintains blood glucose by
acting as another energy source to spare glucose
Gluconeogenesis can start from what three molecules
lactate, glycerol, amino acids
Lactate common source
Red blood cells (anaerobic glycolysis)
Glycerol common source
Released from lipolysis
Amino acid common source
protein degredation in muscles
Ways adipose tissue sustain the body during a fast
oxidize fatty acids for energy, convert fatty acids to ketone bodies
In a short term fast, ketone bodies are used primarily by
skeletal muscle
In a long term fast, ketone bodies are used primarily by the
brain
Lipolysis triggers
stress hormones from exercise and glucagon
Triglycerides use
Glycerol goes to liver for gluconeogenesis
Fatty acids go to the liver for ketone body synthesis
Fatty acids go to other tissues for energy oxidation
Long term fast changes
Muscles: Decrease KB use and increase FA use
Liver: Increases KB production
An increase to KB in the blood decreases the overall need for
glucose
in a long term fast, almost all KB are going to the
brain
In a long term fast, almost all gluconeogenesis is supported by ___________ from the _____________ tissue
glycerol; adipose
In a short term fast, nitrogen excretion is
high
In a long term fast, nitrogen excretion is
low
In a long term fast, protein degredation
decreases
In a long term fast, gluconeogenesis occurence
decreases
In a long term fast, ketone body production
increases
Enzyme activity
Hormone → Signal transduction → activity of enzyme
Enzymes act as
catalysts
Regulation of an enzyme pathway depends on the ability to
flux through the pathway
Three mechanisms for regulating enzymes
One: Substrate/ product concentration
Two: Regulation by changing the conformation of the active site
Three: Change enzyme concentration
Products ___________ their enzymes
inhibit
Velocity of an enzyme is dependent on the
concentration of substrate
Maximum velocity
maximum rate of a reaction
Km
half of the maximum velocity
Concentrations of substrate below the Km are more sensitive to
concentration changes
Isoenzymes
enzymes that have the same substrates and products but have different affinities for the substrate and thus different Km values
High Km means the affinity is
low
Low Km means the affinity is
high
Allosteric
a molecule bonds to an enzyme somewhere other than the active site, acitivating or inactivating the enzyme
in the presece of an activator, the concentration of the substrate to meet the Km is
lower
Activators _________ the affinity for an enzyme
increase
Inhibitors ___________ the affinity for an enzyme
decrease
Advantages of allosteric activation
don’t occupy active site
don’t need to look like substrate/ product
Acts quickly
Phosphorylation of an enzyme occurs by
protein kinase A
Phosphorylation can either ____________ or _________________ an enzyme