- reserve oxygen storage

- oxygen transport in rapidly respiring muscle

• hyperbolic
• has more affinity for oxygen, but doesn't like to let go
• acts like a Michaelis-Menten enzyme
• [image]

• contains protoporphyrin IX and Fe²⁺
• sequestered deep within protein --> protected from carbon monoxide
• optimal environment for reversible osygen binding
• iron atom in center of p IX; bound with N of His
• iron binds with oxygen, which shifts the His residue, causing a conformational change

• has four polypeptide subunits - 2α, 2β
• exists in 2 conformations: T or R
• has cooperative oxygen binding

• "tense" structure
• has salt bridges between α and β subunits
• low oxygen affinity

• "relaxed" form
• has fewer salt bridges; formed by the disruption of these bridges
• high oxygen affinity

• due to the cooperativity of oxygen binding - O₂ binding to one subunit facilitates binding to remaining subunits, causing T --> R
• sigmoidal curve
• acts like an allosteric enzyme
• readily binds to AND releases oxygen
• [image]

2,3-bisphosphoglycerate

• very negatively charged
• only binds to T-state to 3 positive charges on each β-chain
• stabilizes the T-state and allows oxygen to be released in adjacent molecules
• has different binding sites in adults and fetuses (2 γ instead of β); γ has Ser instead of His and has lower BPG affinity but higher O₂ affinity
• also involved in altitude acclimation

• CO₂ in tissue diffuses to red blood cells
• buffering system in red blood cells increases hydrogen concentration; shift to T-state

*If you lower pH:

- lower O₂ binding

- increase [H⁺]

- increase protonation of His on β-chains

- allows formation of salt bridges to stabilize T-state

*CO₂ also lowers O₂ binding by reacting with N-termini to form carbamate, allowing salt bridge formation to stabilize the T-state

Tissues have higher [CO₂] and lower [H⁺]

• position 6 in β-chain is changed from Glu to Val [acidic --> hydrophobic]
• HbS, therefore, has a new hydrophobic surface and interacts with other hydroiphobic surfaces of RBCs
• this is true only for deoxygenated Hb
• results in long, insoluble chains of hemoglobin, with fewer, abnormal, and aggregated RBCs

1. energy stores/fuels
2. structure of DNA/RNA [backbone]
3. structural elements [cellulose, extracellular matrix]
4. cell-cell communication [sugar code]

simple sugar; a carbohydrate with a single aldehyde or ketone unit, i.e. glucose

• carbonyl + 2 or more hydroxyl groups
• has 3-7 carbons
• (CH₂O)_n
• 2 major classes: aldose or ketose
• exist as isomers
• asymmetric carbons

• different monosaccharides linked at any of several OH groups
• α or β conformation at the anomeric carbon
• possibility of extensive branching
• modified monosaccharides

>proteins that bind CHO by multiple weak interactions; weak interactions = specificity

>important for cell-cell interactions

(targeting, adhesion, and signaling)

>i.e. stepping on a tack - selectin flags immune system; E.Coli express lectin that binds to CHO on intestinal walls; embryos express a selectin for binding to endometrium

formed between the hemiacetal group of a saccharide  and the hydroxyl group of some organic compound such as an alcohol or amine at the anomeric carbon

α - the organic group binds below the plane of the sugar

β -  the organic group binds above the plane of the sugar

[image]

heteropolymers of modified monosaccharides; have repeating disaccharide units with one amino sugar and one negatively charged group [which attracts water]

i.e. Hyaluronan - have about 50,000 repeats; a joint lubricant

a protein core attached to glycosaminoglycans

i.e. collagen and aggrecan, which forms a cushion due to water attraction

[image]

enzymes that form glycosidic bonds between specific sugars resulting in oligo- or polysaccharides;

synthesize A and/or B groups on red blood cells[image]

• storage of energy, fuel
• structure of membranes
• signals, cofactors

1. Free Fatty Acids
2. Triacylglycerols
3. Phospholipids
4. Glycolipids
5. Steroids

glycerol

3 fatty acids

[image]

- storage - highly concentrated; about 6.75x more per    gram than glycogen

- very non-polar/hydrophobic

- reduced - lots of potential energy

- can be saturated or unsaturated

AKA oleate

less reduced molecule with double bonds within the fatty acid carbons

the double bonds are almost always cis

• the length of the hydrocarbon chain (14-24);       the greater the length, the lower water stability and higher melting point
• degree of unsaturation (number of double bonds); the greater the degree of unsaturation, the lower the melting point

Saturated fatty acids are solid at room temp,

while unsaturated are liquid at room temp.

1. Phospholipids
2. Glycolipids
3. Steroids/Cholesterol [which also have a signalling role]

Phospholipid Precursor

[image]

- has sugar instead of phosphate

- always on extracellular surface of membranes[image]

• membrane component
• digestion of lipids
• hormone precursor [signalling]

Components:

steroid nucleus, hydrocarbon tail, hydroxyl group

[image]

Characteristic of membrane lipids, which have both a polar and non-polar nature

This applies to phospholipids glycolipids, and cholesterol to some extent

- primarily lipids (phosphoglycerides and sphingolipids) and proteins

- form spontaneously

- hydrophobic tails inside are closely packed due to Van der Waals interactions

- impermeable to ions and polar molecules

- regulate what passes through by inserting proteins

- embedded in and span the membrane

i.e.

- the most common motif: α-helices containing non-polar/hydrophobic residues

- Porins = β-sheets that curl around to form a cylinder; the outer R groups are hydrophobic and interact with lipids; the inner R groups are polar or charged and allow other polar/charged molecules to pass through - the nucleotide sequence alternates which R groups stick out/in

• theory of the membrane which states that the membrane is a solution in which components diffuse - the surface is always changing
• also states that membranes are asymmetric; the inner and outer surfaces [leaflets] have different components - glycolipids are only on the outer; proteins never flip-flop

In the absence of other forces, a solute will diffuse down its concentration gradient until it establishes an equilibrium

- independent for each solute

- sometimes enabled by channels [facilitated diffusion]

• requires a specific membrane protein = channel
• thermodynamically downhill
• passive transport
• faster without a carrier
• slower than simple diffusion
• i.e GLUT 1

glucose transporter that works using facilitated diffusion [passive transport]

• glucose is polar, so the inner R groups of the channel are polar
• fully reversible
• cannot accumulate glucose over outside concentration; reaches equilibrium
• saturable and specific - it only transports glucose and can only handle a certain amount of glucose at a time

a passive transport system that allows millions of ions to flow down its concentration gradient per second - is very fast

• selective for specific ions
• responsive to chemical or physical stimuli; does not open randomly

An ion channel that works through facilitated diffusion/passive transport and is selective for K+

• opening is too small for water
• originally, K+ has a water shell; once stripped, it can pass through the channel
• a specific opening for a specific substance!

An integral membrane protein enzyme that hydrolyzes ATP by pumping Na+ and K+ ions against their concentration gradients [active transport].

>There is high [Na+] outside and high [K+] inside.

>Pumps 3 Na+ out and 2 K+ in, which is not spontaneous, but coupled with ATP hydrolysis it is.

>generates an electrochemical gradient (membrane potential)

a voltage; free energy stored as electrochemical gradients across membranes

used in:

- nerve cell function

- muscle cell excitability

- secondary active transport

a gradient formed by active transport used to drive co-transport of another solute against its concentration gradient

-antiporters

-symporters

i.e. lactose permease

a co-transporter of secondary active transport that couples the flow of one solute downhill to uphill transport of another in the opposite direction

[image]

Co-transporter of secondary active transport that couples the flow of one solute downhill to uphill transport of another in the same direction

[image]

A symporter for secondary active transport that uses free energy stored in the H+ gradient to power lactose uptake

• gets lactose into bacterial cells to be used as fuel
• (+) ΔG
• carboxyl group gets protonated when open to extracellular environment, allowing lactose to bind and cause a conformational change, releasing lactose to the inner cell
• H+ leaves carboxyl, giving another conformational change

1. Release of primary messenger - stimulus triggers release of chemical signal
2. Primary messenger binds to a receptor on target cell, leading to a conformational change
3. Second messenger delivers signal inside the cell; allows amplification and signal spread
4. activation of effectors leading to a cellular response
5. termination of the cascade

largest class of cell surface receptors, including receptors for hormones, neurotransmitters, photons, and odorants

Structure:

• 7 transmembrane α-helices connected by loops
• N-terminus is extracellular, C-terminus is intracellular
• ligand binding site is formed by tertiary structure on the extracellular side
• intracellular loop interacts with G protein
• regulated by ligand binding, leading to a conformational change

• heterotrimeric: 3 subunits

α - binds nucleotide GDP or GTP; intrinsic GTPase, anchored to membrane; interacts with receptors, other proteins; the on/off switch

β - regulates α; tightly associated with γ

γ - regulates α; anchored to membrane; tightly associate with β

• several classes:

G_s [stimulatory], G_i [inhibitory, G_q, G_φ

differ by α subunits and receptors

1. A ligand binds to the GPCR, which causes a conformational change, opening the α binding site 
2. GDP leaves the binding site and GTP enters
3. The α subunit loses its affinity for βγ and the receptor, and it dissociates and diffuses along the plane of the membrane
4. The activated G Protein α subunit interacts with other proteins

*an amplification step

[image]

An integral membrane protein enzyme that catalyzes the synthesis of cAMP, a secondary messenger. It interacts with ATP and the dissociated α subunit with GTP to form cAMP and PP_i [pyrophosphate].

*an amplification step

[image]

A cAMP-activated effector also known as

cyclic AMP - dependent protein kinase that sticks phosphate to amino acids with hydroxyl groups [serine, threonine, and tyrosine], particularly Ser and Thr.

Structure:

2 catalytic subunits [C]

2 regulatory subunits [R]

cAMP binds to R and dissociates, activating C

[image]

• the receptor
• the G protein
• Adenylate cyclase
• PKA

The receptor/ligand interaction is reversible.

The likelihood of dissociation depends on the concentration of the ligand.

A receptor not bound to a ligand can no longer activate G proteins.

Dehydration resulting from diahrrea due to the blockage of the G_sα reset mechanism.

The modified alpha subunit "A" prevents GTP hydrolysis by putting ADP. The A subunit is active and produces an inability to regulate water reabsorption in the intestines.

An enzyme that degrades cAMP to AMP, essentially lowering adenylate cyclase activity/efficacy. This leads to a rapid decrease in the concentration of cAMP, the second messenger.

It is always active at low levels.

It is a means of terminating the Epinephrine cascade.

Inhibitory G protein is activated when the alpha subunit is bound to GTP. it inhibits adenylate cyclase; therefore:

- decrease in AC activity

- decrease in cAMP concentration

- decrease in PKA activity

1. activated by G_q-linked receptors
2. the activated alpha subunit binds to and activates Phospholipase C [PLC]
3. PLC cleaves membrane phospholipids into 2 second messengers:
   • Diacylglycerol [DAG] - the hydrophobic tails
   • Inositol Triphosphate [IP₃] - the hydrophilic heads
4. DAG and IP₃ activate an effector:
   • IP₃ binds to ER receptors, opening Ca²⁺ channels, allowing flow into cytosol
   • DAG and Ca²⁺ activate Protein Kinase C

1. Perform mechanical work.
2. Maintain active transport.
3. Synthesize macromolecules.

how readily a molecule gives up its terminal phosphate

- the more negative Δ G, the more potential it has

1. Chemiosmotic - uses energy stored in a H⁺ gradient to power the addition of P_i to ADP
2. Substrate-level phosphorylation - direct transfer of a phosphate from another, higher energy molecule

1. Nicotinamide Adenine Dinucleotide [NAD⁺] - can accept 2e- and 2H+
2. Flavin Adenine Dinucleotide [FAD]

CoA

a carrier of fragments with 2 carbons used in catabolic and anabolic pathways 

the carriers are stable even though they have a negative delta G; they would break down otherwise

1. Control the amounts of enzymes; the synthesis and degradation
2. control catalytic activity; reversible allosteric modulation [feedback inihibition] or reversible covalent modification [phophorylation]
3. regulate substrate availability; compartmentalization or substrate flux via transporters

A protein hormone secreted by the pancrease that requires a specific receptor on cell membranes.

*focus on function of glucose uptake

• dimer of two identical proteins
• α subunit
  • completely extracellular
  • forms the insulin binding site
• β subunit
  • membrane-spanning
  • intrinsic protein kinase activity           [tyrosine kinase]
  • intracellular

tyrosine kinase phosphorylizing IRS

PI3-K making PIP3

PDK activating akt

dephosphorylation:

phosphatase inactivates kinase enzymes by taking phosphates off, leading to the end of the signals

low pH denatures most proteins

pepsin - protease which breaks dwn polypeptides

residual proteins, oligopeptides are pushed into the small intestine

Pancreas secretes zymogens - an enzyme precursor, inactive until proteolysis or they will destroy other proteins

Peptidases on the external surfaces break oligpeptides into individual amino acids

requires specific enzymes which break the glycosidic bonds

i.e. dextrinase, maltase, α-glucosidase,

α- amylase [only 1-4]

-begins in the small intestine

-emulsification using bile salts, which inserts itself in the droplets and makes smaller by its polar cmponents

-lipases attach to smaller droplets and cleave the fatty acids off the glycerol backbone