Lecture 36 Flashcards
Intro to Human Metabolic Design
bioenergetics
describes the transfer and utilization of energy (energy flow) in biological systems -> think about mitochondria
pg 944
free energy change (Gibbs free energy, ΔG)
a quantitative measure of the energy transfers between chemical reactions; can predict if the reaction will take place
pg 945
enthalpy change (ΔH)
a measure of the change in heat content of the reactants and products (heat released or absorbed during a reaction)
pg 945
entropy change (ΔS)
a measure of the change in randomness or disorder of reactants and products
pg 945
free energy change
- reactants must undergo a transition state with a higher energy level
- exergonic reactions: products have a lower energetic state -> ΔG is negative -> favorable reaction
- endergonic reactions: products have a higher energetic state -> ΔG is positive -> unfavorable reaction as they need added energy to take place
- The net ΔG = 0 when the reactant and product reach equilibrium
pg 946-948
ΔG and reactant concentration
- nonequilibrium reactions: [A]»[B], ΔG < 0, forward reaction will take place until equilibrium is reached
- standard conditions: [A]=[B], ΔG could be positive or negative
- equilibrium conditions: ΔG=0, concentrations likely not equal
- ΔG of a reaction is also dependent on the concentration of the reactants
pg 949
energy changes of metabolic pathways
watch lecture
- when the overall ΔG = ΔG1+ΔG2+ΔG3 is negative the pathway can proceed even if some ΔG of individual steps are positive
- the actual rate of the pathway depends on the activity of the enzymes that catalyze each step
pg 950
coupling of reactions
couple reactions with overall negative ΔG allow for the unfavorable reaction to proceed (ATP->ADP often coupled with unfavorable metbolic reactions to drive them forward)
pg 951-953
metabolism
a term used to describe the interconversion of chemical compounds in the body, the pathways taken by individual molecules, their interrelationships, and the mechanisms that regulate the flow of metabolites through the pathways
pg 955
overview of human metabolism
- energy-yielding nutrients -> catabolism -> energy-poor end products (catabolism releases chemical energy, ATP, NADH)
- precursor molecules -> anabolism -> complex molecules (takes energy extracted from catabolism to undergo anabolism)
- only separation of pathways is done by compartmentalization and substrate availability
pg 956
catabolism
- releases and captures energy in the form of ATP or reduced compounds (i.e. NADH, NADPH)
- allows nutrients to be converted into building blocks to be used for the synthesis of complex molecules of the body
- convergent pathway
- many precursors lead to a common intermediate
pg 957
catabolic pathways
- energy-yielding nutrients undergo digestion and absorption to be broken down into building blocks of macromolecules
- an activation step occurs (needed for molecules to enter a certain catabolic pathway) and then catabolism occurs
- catabolism leads to a common intermediate -> frequently acetyl-CoA which enters citric acid cycle
- citric acid cycle is the central metabolic pathway -> it is amphibolic (both catabolic and anabolic) and provides intermediates for anabolic pathways
pg 958
anabolism
- combines small molecules, such as amino acids, to make complex molecules, such as proteins
- requires energy which can be provided by: ATP or NADH or NADPH (provide electrons for chemical bonds)
- anabolism is a divergent process in which a few common biosynthetic precursors form a wide variety of complex products
pg 959
metabolic maps
help you see all the pathways and how they interact
pg 961
carbohydrate metabolism
- glycolysis (central pathway for all others)
- gluconeogenesis (GNG)
- glycogen metabolism
- fructose and galactose
pg 962
carb metabolism -> TCA and ETC
- Krebs cycle (TCA)
- oxidative phosphorylation
- electron transport chain (ETC)
pg 963
lipid metabolism
- beta-oxidation
- FA synthesis de novo
- TAG, PL, and SL metabolism
- cholesterol homeostasis
- lipoprotein metabolism
pg 964
nitrogen metabolism: amino acids
- AA metabolism
- nitrogen disposal
- other nitrogen-containing compounds
pg 965
nitrogen metabolism: nucleotides
- purine and pyrimidine metabolism (how they’re produced)
pg 966
nitrogen metabolism: porphyrins
- heme synthesis
- heme degradation
- porphyrin metabolism
pg 967
metabolic requirements for life
- ability to synthesize everything that is not supplied by the diet but required for survival
- ability to protect our internal environment from: toxic xenobiotics and external environmental changes
- To meet these we metabolize dietary components using 4 types of metabolic pathways: fuel oxidation, fuel storage, biosynthesis, detoxification (extract energy from nutrients we consume)
pg 968
regulation of human metabolism
- flux of metabolites through a pathway (relates to availability of substrates)
- enzyme activity (determines rate of pathway)
- interconversion of metabolic fuels (from one type to another)
pg 970
metabolic flux
the rate of turnover of molecules through a metabolic reaction or pathway
- equilibrium reactions (reversible): the forward and reverse reactions occur at equal rates and there is no net flux in either direction (lowest possible energetic state)
- nonequilibrium reactions (nonreversible): reactants are present in concentrations that are far from equilibrium
- “steady-state” conditions: net flux from left to right because there is a continuous supply of substrate A and continuous removal of product D
pg 971
principles of pathway regulation
- rate-limiting reaction
- committed step in a pathway
- feedback regulation
- feedforward regulation
- product inhibition
pg 972
well-fed/absorptive state
Priorities
- maintain blood glucose levels within healthy range
- replenish lost glycogen and lipid stores, and proteins
- Timing: 2-6 hours after ingestion of a normal meal
- Plasma: increased glucose, AA, and TAGs in chylomicrons
- Pancreas: increased insulin (signal of well-fed state), decreased glucagon release
- Tissues: increased synthesis of glycogen, TAGs and proteins
pg 974
fasting/post-absorptive state
Priorities
- maintain blood glucose level for tissues requiring glucose (brain, RBCs)
- mobilize FAs from adipose tissue and ketone bodies from liver to supply energy to all other tissues
- Timing: > 6-12 hours after ingestion of any food
- Plasma: decreased glucose, AA, and TAGs in chylomicrons
- Pancreas: decreased insulin, increased glucagon (signal of lack of glucose) release
- Tissues: increased degradation of glycogen, TAGs and proteins
pg 974
interconversion of metabolic fuels
- happens in 4 major tissues: adipose tissue, muscle, blood, and liver
- carbs in excess of the needs of the body can readily be used for synthesis of FAs, incorporated into TAG and stored adipose tissue (and liver)
- FAs in excess are stored predominantly in the adipose tissue as TAGs
- Acetyl-CoA cannot be used in gluconeogeneis and synthesis of glucose; glycerol CAN
- AAs could be used to produce glucose OR ketone bodies
pg 975
