Test 2 Flashcards
What are some of the uses for motor proteins we discuss?
Organelle migration, motion of flagella, movement of some proteins along DNA
Describe the steps of myosin/actin binding
- Resting State
- Myosin heads are “cocked” and attached to ADP and an inorganic phosphate (Pi), but they are not yet bound to actin.
- Tropomyosin is blocking the active sites on actin, preventing myosin from binding to actin. This is controlled by troponin, which binds calcium ions when released from the sarcoplasmic reticulum (SR). - Calcium Ion Release
- When an action potential reaches the muscle, calcium ions are released from the sarcoplasmic reticulum into the cytoplasm.
-Calcium binds to troponin, causing a conformational change in the troponin-tropomyosin complex. - Exposure of Binding Sites
- The conformational change in the troponin-tropomyosin complex shifts tropomyosin away from the myosin-binding sites on the actin filament.
This exposes the binding sites on actin, allowing myosin heads to bind to actin. - Cross-Bridge Formation
- The myosin heads, which have ADP and Pi bound, now attach to the exposed binding sites on actin. This forms the cross-bridge between myosin and actin. - Power Stroke
-Once the myosin head binds to actin, the release of Pi from myosin causes a conformational change in the myosin head, pulling the actin filament toward the center of the sarcomere. This is the power stroke.
-This action generates force, causing the sliding of the actin filament relative to the myosin filament, which leads to muscle contraction. - ADP Release
-After the power stroke, ADP is released from the myosin head. - ATP Binding and Myosin Head Detachment
-A new molecule of ATP binds to the myosin head, causing the myosin head to detach from the actin filament.
-The ATP is hydrolyzed into ADP and Pi, which re-cocks the myosin head, readying it for another cycle of binding and pulling.
Describe the structural details of myosin
- Six subunits: 2 heavy and 4 light chains
- Fibrous and globular domains
- Aggregate to form thick filaments
- Cleavage by trypsin and papain
- Trypsin cleaves the light fibrous
tail from the globular heads
and then the two heads are
cleaved from each other by
papain
Describe how actin comes into play
Actin is involved in muscle contraction.
- Monomeric actin, G-actin (G for globular), associates to form F-actin (F for filamentous)
-F-actin assembly is driven by ATP hydrolysis
-F-actin along with troponin and tropomyosin comprise the thin filament
-1:1 ratio between actin monomers and myosin head groups
-Muscle contraction occurs from thick filaments sliding along thin filaments
How do tropomyosin and troponin regulate the nerve impulses related to muscle contraction
Troponin and tropomyosin are in complex
- Troponin is a Ca2+ binding protein
- The nerve impulse causes Ca2+ release and subsequent structural changes, exposing myosin binding sites
What do enzymes do?
Catalyze reactions
Enzymes are central to every biochemical process
How do enzymes bind substrate?
Through geometric and electronic complementarity
Name the seven types of enzymes and what they do
Classified according to reaction type:
- Lyases: Addition of groups to double bonds or formation of double bonds by removal of groups
- Isomerases: Transfer of groups within molecules to produce isomeric forms
- Ligases: Formation of bonds by condensation reactions coupled to ATP cleavage
- Hydrolases: Hydrolysis reactions: Transfer of functional groups to H2O
- Oxidoreductases: Transfer of electrons
- Transferases: Group transfer reactions
- Translocases: Facilitate the movement of molecules, such as proteins or other substances, across cellular membranes
What is the enzyme suffix?
-ase
Give the scheme for a simple enzyme catalyzed rxn which converts a single substrate into a single product.
E+S <–> ES <–> EP <–> E+P
Do enzymes affect the rxn equilibria?
No. They just lower the activation energy, thereby speeding up the reaction
- Accelerate interconversion of S and P. The free energy used to lower activation energy comes from binding energy
What does the equilibrium constant Keq describe?
The equilibrium between S <–>P
K’eq= [P]/[S]
When is binding optimal between E and S?
In the transition state.
- Weak binding interactions between E and S provide a substantial driving force for catalysis, creating net lower activation energy
- Binding energy also gives specificity
What does the Rate of product formation depend on?
Activation energy
Define Km
Km: Substrate concentration at which an enzyme-catalyzed reaction proceeds at ½ its maximum velocity
Define V0
Vo: Initial rate or velocity of an enzyme reaction during which [S] does not change drastically
Define Vmax
Maximum velocity of an enzyme reaction when the binding site is saturated with substrate
Define Kcat
kcat: Number of substrate molecules converted to product in a given amount of time on a single enzyme molecule (turnover number)
Complex function of several rate constants - dependent on the rate limiting step!
What are the types of reversible enzyme inhibition?
Competitive
Uncompetitive
Noncompetitive (mixed)
What do enzyme inhibitors do?
- Reduce enzyme efficiency
- Can be good drugs if they inhibit
essential (viral or bacterial)
enzymes - Reversible or irreversible
Define Competitive Inhibition
- Inhibitor binds in the enzyme active
site – competes with normal
substrate binding (forms EI
complex) - Prevents substrate from binding
and reacting - Usually looks like substrate (or
transition state of reaction!)
Describe competitive inhibitions effect on kinetics
Vmax remains constant
Km increases
- Dependent on alpha
Apparent Km: aKm
Define uncompetitive inhibition
Inhibitor binds to enzyme-substrate complex at site distinct from active site
Distorts the active site making it inactive via conformational change
Describe uncompetitive inhibition effect on kinetics
Vmax & Km decrease
Both dependent on a’
Apparent Km: Km/a’
Apparent Vmax: Vmax/a’
Define Mixed/Noncompetitive Inhibition
Inhibitor binds to either E or ES
Rarely seen …
Describe Mixed/Noncompetitive Inhibition effect on kinetics
Vmax decreases
Km may increase or decrease
Apparent Km: aKm/a’
Apparent Vmax: Vmax/a’
Describe covalent catalysis
Amino acid side chain is often the nucleophile in a reaction, becoming transiently attached to the intermediate
Undergoes further reaction to regenerate free enzyme
Serine and cysteine are most common
What kind of protease is Chymotrypsin
A serine protease
Describe the differences between cysteine and serine proteases
Cysteine
- Cathepsins
B & L: Involved in cancer growth
and metastasis
K: Important for bone
degradation and osteoporosis
- Caspases
11 identified in humans thus far
Play a role in apoptosis,
necrosis, & inflammation
Serine
- Digesting enzymes
Trypsin & chymotrypsin are
found in the small intestine
Elastase is secreted from the
pancreas
- Coagulation enzymes
Factor VIIa, Xa, & thrombin are
found in blood
What are coenzymes?
- Organic or metalloorganic molecules
- Coenzymes often work by binding to the enzyme and helping it to facilitate a chemical reaction, typically by transferring chemical groups between molecules.
- Often involved in redox reactions
- Important in metabolic pathways
- Must be regenerated to complete catalytic cycle
- May be transiently or permanently associated with the enzyme
Example: Heme porphyrin
What is a cofactor?
Metal ions
Ionic interactions between metal and substrate orient the substrate for reaction
Facilitate catalytic process
May also stabilize charged transition states
Participate in oxidation-reduction reactions
Give an example of a cofactor
Zinc Proteases
Zn2+ stabilizes tetrahedral intermediate during amide bond hydrolysis
Give an example of a coenzyme
NAD+
NAD+ is reduced to NADH during an enzyme-mediated oxidation reaction
Describe how induced fit dictates substrate specificity and chemistry
The induced fit model describes how the enzyme’s active site undergoes a conformational change upon binding to its substrate. Unlike the earlier lock and key model, where the enzyme and substrate have complementary shapes before binding, the induced fit model suggests that the enzyme’s active site is flexible, and when a substrate binds, it induces a change in the enzyme’s structure to better fit the substrate.
The flexibility of the active site allows the enzyme to recognize and bind a broader range of substrates, as it adjusts to accommodate the specific shape of each one.
The induced fit helps ensure that only the correct substrate can induce the proper structural changes in the enzyme, thereby enhancing the enzyme’s selectivity.
Describe how interactive complementarity dictates substrate specificity and chemistry
Interactive complementarity refers to the non-covalent interactions between the enzyme and its substrate, such as hydrogen bonds, ionic interactions, hydrophobic interactions, and van der Waals forces.
The enzyme specifically recognizes substrates through complementary shape and charge distribution. The enzyme’s active site has a precise arrangement of amino acid residues that interact with particular features of the substrate (such as functional groups or charge patterns).
What are the two types of nucleic acids
DNA
RNA
What are the different types of RNA and what do they do?
- rRNAs make up the ribosome,
- mRNAs give the info for protein
synthesis to the ribosome - tRNAs are adaptor molecules that
decipher mRNA and translate it into
amino acids
Describe the structure of DNA
A double helix that stores genetic information
*Antiparallel
*Complementary strands
*Major & minor grooves
*Stabilized by weak interactions
*3.4 Angstroms between adjacent
bases
*Watson, Crick & Wilkins - 1953
*Nobel prize: 1962
What are the key components of DNA?
3 Key Components:
*Nitrogenous base
*Pentose sugar
*Ribose/deoxyribose
*β-furanose form only
*Phosphate group
Nucleosides are nucleotides without
the phosphate
How is DNA stabilized?
Hydrogen bonding between base pairs
* Hydrophobic effects
* Stacking of hydrophobic
purines/pyrimidines on helix
interior
* Sugar-phosphate backbone
solvent exposed
* Charge-charge interactions
* Negative charge of phosphate
backbone typically countered in
vivo by Mg 2+
* Repulsion also minimized by
cationic proteins
What does H bonding between base pairs in DNA allow for?
Width Conservation
It also creates minor and major
groove
- Chargaff’s rules= A+G = T+C
- “The sum of purine bases is
equal to the sum of pyrimidine
bases”
What does the nucleic acid
backbone alternate between?
A pentose and phosphate group.
Phosphate-group bridges one nucleotide to the next, called phosphodiester linkage
- Backbone is hydrophilic (both RNA
and DNA) - Bases are hydrophobic
What are the purines?
Adenine and Guanine
What are the pyrimadines?
Thymine, Cytosine and uracil
What is the difference between a deoxyribose and a ribose sugar
Ribose: Has a hydroxyl group (-OH) on the 2’ carbon.
Deoxyribose: Lacks the hydroxyl group on the 2’ carbon (it only has a hydrogen atom (-H)).
What do DNA mutations cause?
Aging and pathogenesis.
Hydrolysis of N-beta-glycosyl bond
between the base and pentose
causes loss of base, or creation of a
DNA lesion (aka AP: apurinic,
apyrimidinic)
- Purines are lost at a higher rate
than pyrimidines
- Deamination (loss of exocyclic amino group)
- UV radiation
How does the cell use DNA
methylation?
Methylated bases are useful
- for distinguishing self DNA from foreign
- For distinguishing between new DNA and old
- For modulating gene expression (epigenetics)
How can RNA make double stranded structures?
Hairpins, complex loops, double-
stranded regions where it folds back
onto itself
Why is RNA less stable?
The 2’ OH
Has increased susceptibility to hydrolysis.
What are other uses for nucleotides?
ATP is central carrier of chemical energy in cells
* Cyclic AMP is a common second messenger produced in response to hormones and chemical signals
* ATP and ADP serve as neurotransmitters
* Coenzymes contain adenine nucleotides (CoA)
What is a palindromic sequence?
Regions of DNA that have inverted repeats
→ Self-complimentary sequence repeated in the opposite orientation of paired strand
→ When the self-complimentary sequence occurs in both strands of DNA, it’s a mirror repeat
Hairpins and cruciforms form in nucleic acids because of ____
palindromic sequences
RNA can form into different structural levels like proteins. Describe these levels
Primary: nucleotides in a sequence
Secondary: folded chain of nucleotides with single-stranded and helical double-stranded regions.
Tertiary: pseodoknot folding
Quaternary: Can be either RNA-RNA interactions or RNA-protein interactions.
What makes sugar sweet?
Carbs
What are the most abundant biomolecules on earth?
Carbs.
What is the central energy-yielding
pathway in most non-photosynthetic cells?
Oxidation of carbohydrates
What serves as structural and protective elements in bacterial, fungal, and plant walls
Carbohydrate polymers
What are the 3 major size classes of
carbohydrates?
Monosaccharides: aka
simple sugars; consist of a
single polyhydroxy aldehyde
or ketone unit
Oligosaccharides: short
chains of monosaccharide
units joined by characteristic glycosidic bonds
Polysaccharides: sugar polymers containing 10 or more monosaccharides units
Monosaccharides are
either ____ or ____
aldehydes or ketones with two or
more hydroxyl groups
If the carbonyl group is at the
end of the carbon chain, the
monosaccharide is an aldose
(aldehyde)
If the carbonyl group has two R-
groups (i.e. is in any other
position in the monosaccharide)
then it is a ketose (ketone)
What is the number of carbon atoms in the backbone is indicated by?
The naming mechanism
Are monnosachharides chiral?
Yes.
Almost all hexoses are D isomers
Ketoses have one less chiral carbon than aldoses
What are Epimers?
They differ at one chiral center.
Note that by convention, the carbons are numbered beginning at the end of the chain nearest the carbonyl
What does circularization create?
Additional stereoisomeric conformations
What are anomers?
Isomeric forms of monosaccharides that differ only in their configuration around the hemiacetal or hemiketal (i.e. carbonyl) carbon
What can create alpha and beta
stereoisomeric configurations?
Because the alcohol can form the bond in two ways, attacking from either the front or back or the carbonyl carbon, this creates alpha and beta stereoisomeric configurations
Describe the steps of Extrapolating Fischer projections to circular
structures: Haworth perspective formula
1) Draw the six membered ring (5 carbons and one oxygen in upper right corner)
2) Number the carbons in a clockwise direction beginning with the anomeric carbon
3) Then place the hydroxyl (OH) group. If it’s to the right in the Fischer projection then it is pointing down (i.e. below the plane of the ring), if left, it’s pointing upward. Once placed, if it’s on the same side of the ring as C-6 then its beta; if opposite then it’s alpha
4) The –CH2OH group projects upward for the D enantiomer, downward for the L enantiomer
Describe a furanose
Alcohol/hydroxyl oxygen on carbon-5 (or 6) becomes ether
* Double bonded oxygen on C-2 becomes an alcohol/hydroxyl
What does oxidation of carbonyl carbon in aldoses produce
Aldonic acids
What does Oxidation of the C-6 carbon lead to
Production of the corresponding uronic acid.
What does Oxidation to produce aldonic acids depend on?
The linear form, can’t linearize if involved in glycosidic bond
How are disaccharides formed?
Through O-glycosidic bonds
Reducing vs non-reducing sugar
Reducing end: free anomeric carbon (not involved in glycosidic bond);
able to be oxidized
Non-reducing sugars are linked at their anomeric carbons; the nonreducing end is the end that will be “plucked” off for energy
What does polymerization lead to?
polysaccarides
In nature what is the form most carbohydrates are found in?
polysaccharides (aka glycans)
How are polysaccharides defined?
- Monosaccharide units
- Length of chains
- Types of bond linking the units
- Degree of branching
Is there a template for polysaccharide synthesis?
No. Thus, no set length or molecular weight
* Driven by the polymerization reaction
What are the most important storage polysaccharides for plant cells?
Starch
What are the most important storage polysaccharides for animal cells?
glycogen
Why would we not store glucose in its monomeric form?
The polysaccharide form allows you to break the bonds to access energy more effectively. It also has branched form, so you can strat cleavage in multiple locations.
What defines the
difference on whether the
glucose polysaccharide gets
used for energy storage or
structural aspects?
Energy storage polysaccharides like glycogen and starch are highly branched to allow rapid mobilization of glucose when energy is needed.
The branches increase the surface area, making it easier for enzymes to access and break down the polymer.
In contrast, structural polysaccharides like cellulose have linear or slightly branched chains that stack together in an organized manner, creating strong and rigid fibers. This provides mechanical strength and resistance to degradation, suitable for structural support in cell walls and exoskeletons.
What is the extracellular matrix (ECM) composed of
An interlocking meshwork of heteropolysaccharides
Polysaccharides also form
________ with other
macromolecules
conjugates
Aside from being energy storage or structural components, they provide and “transmit” information
What are the ways glycoconjugates are formed
N-linked glycosylation is when a
glycan is attached to a protein
via recognition of a motif. The
motif is Asparagine-X-Serine/Threonine where X is any
amino acid except proline. The
glycan is specifically connected
to the nitrogen atom of the
asparagine in this motif.
O linked glycosolation of a
protein occurs when the sugar is
attached to the oxygen molecule
of serine or threonine
What are often toxic to humans
Bacterial lipopolysaccharides
What are lectins important for?
getting lymphocytes to infection or
injury sites. This is accomplished through specific lectin-ligand
interactions
How are Glycosidic bonds are
produced?
hemiacetal groups reacting with another alcohol (in this case,
another sugar)
What are Bacterial cell walls comprised of?
peptidoglycans
True or False:
O-linked and N-linked
conjugation for glycoconjugate
formation is amino acid specific
True
Define active vs passive membrane transport
Passive: diffusion of a solute down its concentration gradient
Active: transport against a concentration gradient and/or electrical potential
How is a transmembrane electrical gradient created?
membrane potential, Vm, is created when ions of opposite charge are separated by a permeable membrane
The electrical gradient + the chemical gradient= ______
electrochemical gradient
What are the four types of ion channel?
- Ligand-gated
- Mechanically- Gated
- Always Open
- Voltage Gated
What are the Structural features of the voltage gated Na+ channels in neurons
- Subunit α is essential
-Contains 4 homologous domains, each containing 6 transmembrane helices
- Segments between helices 5 and 6 create selectivity filter
- Segment connecting domains 3 and 4 is the inactivation gate
- Helix 4 is involved in the voltage-sensing mechanism
What is an example of a ligand-gated ion channel
The acetylcholine receptor
Important to note that acetylcholine is an extracellular ligand.
Both the acetylcholine receptor and the voltage gated Na+ channel relate to _____
Ca2+ transport and ultimately muscle contraction
Describe a few key details about AcH signaling
Acetylcholine is made from acetyl-coenzyme A (a downstream side product of glycolysis) and choline, a reaction catalyzed by choline acetyltransferase
Cholinesterase is the enzyme responsible for breaking down acetylcholine so the muscle can relax (i.e. it attenuates the signal)
The extensive importance of ion channels is best illustrated by ____
the diseases arising from ion channel mutations
True or False:
Membrane proteins decrease the rate of transmembrane solute movement
False. They increase it
Describe if active transport requires energy
Process is thermodynamically unfavorable (endergonic)
Requires either direct or indirect coupling to an exergonic process (i.e. ATP hydrolysis)
Give the important info for ABC Transporters
Also ATP-driven; ABC= ATP-binding cassette
48 human genes encode ABC transporters
Some are really specific for substrates, others more “promiscuous”
Common therapeutic target because of drug transport (export) ability
- MDR1 causes resistance to
antitumor drugs, pumping out
chemotherapeutics like
doxorubicin and vinblastine;
MDR1 overexpression in liver,
kidney, and colon is associated
with treatment failure
- ABCs in pathogenic microbes
contribute to antibiotic resistance
BCRP (breast cancer resistance
protein) is an ABC overexpressed
in breast cancer cells which
confers resistance to anticancer
drugs
Define Uniport
A transporter system that carries only one substrate
Define symport and antiport
Transporter systems that carry two substrates
Sym-same direction
Anti-opposite directions
Describe Glucose Transporter – GLUT1
Passive transporter
Transfers glucose from blood plasma via facilitated diffusion
Integral membrane protein of erythrocytes
12 hydrophobic segments
Assembly provides hydrophilic channel
Define the GLUT1 Mechanism
Two major conformations
T1: Glucose binds to outside & induces a conformational shift
T2: Resulting conformation for glucose release inside cell
Diffusion is favored down the concentration gradient
[Glucose] ≈ 5 mM in plasma
Internalized glucose is metabolized instantly to maintain concentration gradient
Describe the GLUT1 Kinetics
High plasma glucose concentration saturates transporter → Rate of uptake approaches Vmax
Process is fully reversible due to no change in substrate structure
Specific for D-glucose
Explain Diabetes and Glucose Transport
Insulin released from pancrease in response to high blood glucose
Type 1 (insulin-dependent): cannot release insulin and therefore mobilize glucose receptors, resulting in low glucose uptake into muscle and adipose
Type 2: insulin resistant
Define signal transduction
The ability of an organism to detect extracellular signals (information) and transduce them into intracellular changes (response)
This is a universal property of living cells that always involves chemical processes
Many signals and many final responses but few evolutionarily conserved mechanisms of transduction
How did specificity arise in signal transduction?
From molecular complementarity between the signal/ligand and receptor
Certain receptors are only present in certain cell type
How did sensititvity arise in signal transduction?
High affinity of signal and receptor → (Kd < 10-10 M, picomolar range)
What is cooperativity?
Results from large changes in receptor activation with small changes in ligand concentration
What is amplification?
Increase in the signal via activation of additional enzymes in the cascade
What is Desensitization/Adaptation?
Process by which a response ceases after prolonged exposure to the signal
What is Integration?
Multiple signals producing a unified response to maintain homeostasis
Describe an insulin receptor
Receptor Tyrosine Kinase (RTKs) family
Insulin binding activates the Tyr kinase domain
- Auto phosphorylates 3 Tyr on
opposing b subunits
Results in a conformational change that opens the protein binding site
- Tyr kinase domain available to
phosphorylate other target
proteins
Describe Insulin signaling for gene regulation
- IRS-1 binds and is phosphorylated
- P-Tyr interacts with SH2 domain
on Grb2 and results in a series of
binding events to activate RAS
`
- P-Tyr interacts with SH2 domain
- Raf-1, MEK, & ERK are in the MAPK family and produce a cascade to amplify the initial signal
- Attenuation of the signal occurs when insulin levels decrease and/or regulation at any of these targets
ubiquitination
Describe the mechanism for terminating signaling through the PI3K–PKB pathway
A PIP3-specific phosphatase (PTEN in humans) removes the phosphate at the 3 position of PIP3 to produce PIP2, which no longer serves as a binding site for PKB, and the signaling chain is broken.
What do tumor cells typically have?
In various types of advanced cancer, tumor cells often have a defect in the PTEN gene and thus have abnormally high levels of PIP3 and of PKB activity. The result seems to be a continuing signal for cell division and thus tumor growth.
What are oncogenes
Oncogenes encode defective signaling proteins (growth factors, receptors, G-proteins, protein kinases, or nuclear regulators of transcription) driving uncontrolled cell division/proliferation
Oncogenes are genetically dominant
What are tumor supressor genes
Tumor suppressor genes encode regulatory proteins that normally participate in cell cycle checkpoints, inhibiting cell division when damage is present or something is wrong
Mutations in tumor supressors are recessive but can also lead to cancer
True or false: GPCRs are the largest receptor family in mammals
True
How many GPCRs are encoded in genome
800 (3% of genome)
What are the 5 structurally distinct subfamilies of GPCRs. What type are most of them?
Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin
90% are Rhodopsin
What percentage of all identified drug targets are GPCRs?
30%
How many times do GPCRs traverse the membrane?
7
What are common second messengers that interact with GPCRs?
cAMP is most common, but other 2nd messengers are used in common pathways
IP3 is inositol 1,4,5 triphosphate
DAG diacylglycerol (hormone signaling)
Describe the beta-Adrenergic Pathway
Our example of a classical GPCRS
B-adrenergic receptor is specific to epinephrine ligand to induce response; found in muscle, liver, and adipose tissue; induces sugar and lipid metabolism, while also increasing heart rate and respiration – Fight or Flight
Gs activation in caused by a conformational change in receptor and catalyzing replacement of bound GDP to GTP; allows dissociation of a subunit to adenylyl cyclase (AC)AC catalyzed the production of cAMP and acts as a second messenger
cAMP acts as an allosteric activator to protein kinase A (PKA), which catalyzes the phosphorylation of other proteins
Describe the Allosteric Activation of PKA
Protein kinase A: 2 catalytic and 2 regulatory subunits
- Tetrameric complex is inactive
cAMP binding induces
conformational change that moves autoinhibitory domain from catalytic domain
Dissociation yields active catalytic subunits
Give the full summary of the B-adrenergic pathway
Signal: catecholamines (epinephrine and norepinephrine)
Receptor: β-adrenergic
Transducer: G protein
Effector: Adenylyl cyclase
Second messenger: cAMP
Second messenger target: Protein kinase A
Attenuator:
-Cyclic nucleotide
phosphodiesterase breaks
down cAMP
-Drop in epinephrine level (below
Kd) causes dissociation from
receptor
-Hydrolysis of bound GTP to Gα
subunit, Returns Gα to bind to
Gβγ subunits, Ends cAMP
production
-Inactivation of PKA via
phosphatases
-Endocytosis initiated by B-
arrestin
Location: muscle, liver, adipose tissue
Physiological targets:
- Sugar and lipid metabolism
- Respiration and heart rate
