Cell Bio 2 Flashcards
Ex of passive transport vs active transport
simple and facilitated diffusion, osmosis, nonpolar substances pass directly thru bilayer vs primary and secondary active transport, requires energy in order to go against conc gradient
facilitated diffusion
polar or charged substances requiring transport protein to pass directly thru membrane, still moving from high to low conc; involves gated channels and carriers w/ for substrates
Ex of primary vs secondary active transport
using ATP directly to transport molec across membrane, (ex: Na/K ATPase) vs gradient of cmpd A drives cmpd B against their gradient; a cotransport either by symport or antiport (ex: ATP synthase from ETC)
Know what happens w/ CO2/HCO3 in tissues and lungs
it’s an example of facilitated transport
deltaG for simple diffusion vs active transport
neg –> spont vs pos (b/c you require energy) –> nonspont
Na/K pump
Na/K ATPase pumps 3 Na out and 2 K in. But K is high in the cell and Na is high outside the cell –> use ATP to pump K in and Na out => primary active transport
3 types of ion pumps
V type - Vaculolar serve to acidify cellular compartments; ATP hydrolysis energy used to drive H+ transport from low to high conc. P type - phosphorylated by ATP and use energy in phosphate bond to drive transport; always used to drive active transport of ions against conc gradient (ex: NA/K pump and Ca2+ pump). ATP binding cassette (ABC) transporter - use ATP binding and hydrolysis to transport substance across membrane either to bring molec into cell or take molec out of cell (ex: drug transport/metabolite elim)
secondary active transport of glucose
using Na pump (primary transport) to drive glu into cell (secondary transport): in the cell, Na = low and glu = high; out of the cell, Na = high and glu = low –> Na can passively enter cell (high to low conc) but glu uses Na gradient to enter cell (low to high conc). when leaving the cell, Na uses Na/K pump (low to high conc) and glu passively diffuses (high to low conc)
GLUT1 vs GLUT2 vs GLUT3 vs GLUT4 vs GLUT5
1-4 = glucose transporter into cells for glycolysis. in RBCs and barriers, high affinity to glu vs in liver, intestines, kidneys, pancreatic beta cells; low affinity to glu –> bind at high [glu] vs in brain, high affinity to glu insulin-dep glu transport; in adipose, skel and cardiac muscle; high affinity to glu vs fru transporter
What are hormones? and examples?
Signaling molecules secreted from organ/tissues into bloodstream to target other organ/tissues. aa/derivatives, peptides, glycoproteins, steroids, cholesterol and fat derivatives
extracellular vs intracellular receptor
bind peptide hormones (insulin, GH, PTH) and tyr-derived catecholamines (dopamine, nor/epi); almost always act to stimulate signal cascade vs bind steroid hormones (glucocorticoids like cortisol, mineralocorticoids like aldosterone, androgen/estrogen, vit D) and retinoic acid derivatives and thyroid hormones; almost always act on DNA lvl to alter transcpxn
basic steps of signaling (6)
recognition: hormone binds to specific receptor –> transduction: receptor conformational change –> transmission: receptor activate adaptor protein –> modulation: 2nd messenger produced to activate target protein –> response: cell status changes –> termination: degrade 2nd messenger and turn off target protein
autorcrine vs paracrine vs endocrine
signaling self (mobile cells) vs signaling nearby (nerve cells/synaptic cleft) vs signaling far apart
5 classes of receptors and their 3 fxns
ligand gated ion channels, G protein coupled receptors, catalytic receptors, intracellular/steroid receptors, transmembrane proteins that release transcpxn factors. ion channel receptors, receptors that are/bind to kinases, heptihelical (7 membrane spanning helices) receptors
ligand gated ion channels
ligand binds to extracellular domain of membrane spanning receptor –> conformational change –> ion enters cell. acetylcholine Ach bind to Ach receptor –> receptor undergoes conformational change –> opens channel to let K+ in and Na+ out; Ach = terminated by acetylcholinesterase which degrades it
G protein coupled receptors
ligand binds to receptor –> receptor interacts w/ G protein alpha/beta/gamma + GDP (inactive) –> GDP becomes GTP = active –> alpha + GTP = released from G protein beta/gamma –> each set work on targets –> alpha + GTP = hydrolyzed –> GTP becomes GDP –> both sets come together again as G protein alpha/beta/gamma + GDP (inactive)
G alpha subunits: Gs vs Gi vs Gq
Activates adenylate cyclase to inc cAMP (2nd messenger) –> cAMP binds to R subunits of PKA –> releases C subunits –> active C units phosphorylate target proteins via ATP; cAMP phosphodiesterase breaks cyclic bond to produce AMP –> stops signal vs inhibits adenylate cyclase to dec cAMP vs activates phospholipase C to cleave phospholipid from membrane into PIP2 which then gets cleaved into DAG and IP3 –> DAG activates PKC, and IP3 opens Ca channels in ER which inc Ca in cell –> smooth muscle contraction
ex of G proteins
adenylate cyclase (AC), phosphodiesterase, PKA, PKC
cAMP mediated gene transcpxn
cAMP response element bind protein (CREB) binds to cAMP bind protein (CBP) –> forms complexes at cAMP response element (CRE) –> initiates gene transcpxn
ex of heptihelical G protein coupled receptors
cardiac: beta adrenergic receptor - sympathetic stimulation of cardiac fxn like inc HR and contractility, f/light response. vascular: beta adrenergic receptor - sympathetic stimulation leads to smooth muscle relaxation, vasodilation to inc blood flow to tissue. liver: alpha adrenergic receptor - in f/light response, change glu metab to ensure max energy for cells. glu metab: glucagon receptor - signals fasting state –> liberate stored energy to meet energy needs of cells
insulin receptor
insulin receptor = preformed dimer, each 1/2 w/ alpha and beta subunit. insulin binds to receptor –> autophosphorylates –> phosphorylated receptor binds to insulin receptor substrate (IRS) and phosphorylates it –> phosphorylated IRS activates target proteins: Grb2, phospholipase C and PI3-kinase –> PLC cleaves PIP2 to DAG (to activate PKC; mem bound)& IP3 (for smooth mus cxn; soluble); and PI3K phosphorylates PIP2 to become PI 3,4,5, trisP (mem bound) –> activates PDK1 and PKB –> PKB enters cyto and propagates insulin signal
transactivation
something outside is activating into the cell (crossing
barrier); ligand causes conformational change of receptor –> receptor binds to specific DNA segment to start/stop transcpxn (DNA segments = response elements ie. steroid response element or cAMP response element)
lipid vs carb vs protein
9cal/g, primary energy source, more [H] & yield more energy when [O]; TAG = major dietary fat, chol, phospholipid; pathways: FA [O] and synthesis, lipid synthesis vs 4kcal/g, glu = fuel, give intermediates of metab; pathways: glycolysis, glycogen, gluconeogenesis, PPP vs 4kcal/g, can be [O] for energy; precursors for synthesis of nitrogen-containing cmpds (RNA, DNA, Heme); pathways: aa synthesis and degradation
metabolites and central intermediates
any molec involved in synthesis or degradation of biopolymers (metabolic pathway); ex: vit, mineral, glu; 2 CARBON ACETYL GROUP = THE CENTRAL INTERMEDIATE IN MOST ATP PROD PATHWAYS; E- = KEY ENERGY TRANDUCTION COMPONENT OF METABOLIC PATHWAYS (wants to move from neg potential to pos potential)
catabolism vs anabolism
both can happen at same time. breakdown of biomolec; fuels = [O] to CO2 and H2O, NAD+ –> NADH; central intermediate = acetyl CoA vs biosynthesis of biomolec; need energy –> e- = added to molec, NADH –> NAD+
how are metabolic pathways compartmentalized?
w/in cell by restricting pathways to particular organelles (glycolysis in cyto, ETC in mito), w/in certain tissues (lactic acid in muscle, glycogen breakdown in liver); liver = central site of intermediary metabolism
metabolism vs intermediary metabolism
sum of all enzyme-catalyzed rxns in a living org vs set of rxns that take place in cells
deltaG and Keq trends
deltaG < 0 –> spont, Keq > 1
deltaG = 0 –> equil, Keq = 1
deltaG > 0 –> not spont, Keq < 1
which 2 classes of biomolec help w/ energy transfer?
reduced coenzymes (NADH, FADH2) and high energy phosphate cmpds (UTP has high energy, GIP has low energy; ATP has high energy, glu has low energy)
fed state vs fasting state vs starved state
from start of absorption to end of absorption => absorptive state, ~4hrs vs end of absorption to start of next absorption => post-absorptive state –> GI tract = empty –> take energy from stored foods, brain uses ketone bodies vs in fasting state >3d, brain uses ketone bodies
ex of essential fats
alpha/linoleic acid
how are fuels (excess fat vs carb vs protein) stored? how are fuels used?
fuel storage = driven by insulin; converted to TAG and stored in adipose vs most glu converted to glycogen, excess glu converted to TAG and stored in adipose vs aa for protein synthesis, excess protein stored in adipose or elim from body
fuel use = driven by glucagon –> released fuel molec
glucagon vs insulin
fasting hormone secreted by alpha cells of islets of Langerhans in pancreas; major determinant for glu and aa. acts on liver and adipose. glycogen breakdown, gluconeogenesis, FA [O] vs glu hormone (B/C GLU = PRIMARY AGENT FOR INSULIN RELEASE) secreted by beta cells of islets of Langerhans in pancreas; major determinant for glu but minor for aa. acts on liver, adipose, and skel muscle. glycolysis, FA synthesis, protein synthesis
ongoing relationship b/w glu, glucagon and insulin and their goal blood glu
as glu inc –> insulin inc and glucagon dec. as glu is being absorbed from blood to tissue –> insulin dec and glucagon inc. goal: maintain blood glu 80-100mg/dL
what/where degrades insulin vs glucagon?
insulin-degrading enzyme (IDE) for both. liver, kidney, skel muscle vs kidney and a little in liver
what inc vs dec insulin release besides glu? what innervates pancreas?
aa vs epinephrine. pancreas = innervated by ANS (branch of vagus nerve)
signal transduction by glucagon
operates via cAMP-directed phosphorylation cascade: glucagon receptor is G-protein-coupled –> activates adenylate cyclase –> cAMP prod –> cAMP binds to inactive PKA –> activates PKA –> PKA phosphorylates target proteins –> phosphorylates glycogen synthase => inactive –> stops glycogen synthesis OR phosphorylates glycogen phosphorylase => active –> starts glycogen breakdown
phosphorylase a vs phosphorylase b
when glycogen phosphorylase = phosphorylated/active vs when glycogen phosphorylase = not phosphorylated/inactive
signal transduction by insulin
operates via tyrosine kinase activated phosphorylation cascade: insulin receptor autophosphorylates –> activates its kinase activity and phosphorylates targets –> phosphorylated targets activate phosphatase –> phosphatase dephosphorylates glycogen synthase –> start glycogen synthesis/stop glycogen breakdown
epinephrine on metabolism
signals for more glu need for brain, blood, muscle -> similar effects of glucagon. Epinephrine binds to β-adrenergic receptors (G couple protein receptor) or liver alpha receptors –> stimulates adenylate cyclase –> PKA activation –> inc bronchial dilation and pulmonary circulation to enhance oxygen uptake into the blood, inc cardiac contractility and stimulates vascular system for blood flow to tissues (mainly muscle), inc skel muscle blood flow for more oxygen delivery and glucose delivery for more efficient CO2 removal
exer vs neuron signal for glycogen breakdown
muscle contraction –> adenylate cyclase –> cAMP –> PKA –> phosphorylates glycogen phosphorylase –> glycogen breakdown vs nerve impulse –> Ca2+ activates Ca2+-modulin –> phosphorylase kinase –> phosphorylates glycogen phosphorylase –> glycogen breakdown
glycolysis and its two phases
happens in cyto, anaerobic, deltaG neg –> spont; first phase: use 2 ATP to convert glu to DHAP+G3P, second phase: 2 G3P convert to 2 pyruvate and make 4 ATP –> GAIN 2 NET ATP
hexokinase vs glucokinase
in tissue, higher affinity for glu –> do glycolysis even if [glu] = low vs in liver and pancreatic beta cells, lower affinity for glu –> do glycolysis when [glu] = high
phosphofructokinase 1 (PFK-1)
THE committed step of glycolysis, rate limiting step of glycolysis, thermodynamically irreversible, highly regulated (AMP, F2,6P, insulin = pos modulator; ATP = neg modulator)
effect of AMP on glycogen phosphorylase?
inc activation of glycogen phosphorylase
when are 2 NADH vs 2 ATP produced in glycolysis?
when 2 G3P convert to 1,3 BPG via G3P hydrogenase vs when 2 1,3 BPG convert to 3PG via phosphoglycerate kinase AND when PEP convert to pyruvate via pyruvate kinase –> 4 ATP total, 2 NET ATP.
substrate level phosphorylation
when you transfer phosphate group from substrate to ADP –> ATP w/o O2
what happens if O2 or mito = available vs unavailable?
aerobic process, pyruvate goes to TCA cycle –> [O] to CO2 and NADH goes to ETC via G3P shuttle or malate/aspartate shuttle vs anaerobic process, pyruvate converts to lactate and NAD+ via lactate dehydrogenase
goal of TCA cycle
transfer e- to produce NADH and ATP for ETC later –> TCA = dependent on NADH/NAD+ ratio and ATP/ADP ratio; [O] acetyl CoA to CO2 + H2O;
products of full TCA cycle?
[3 NADH, 1 FADH2, 1 GTP, 2 CO2] x2; 9 ATP + 1 GTP
Which two steps of the TCA Cycle are endergonic?
citrate to isocitrate via aconitase, malate to oxaloacetate via malate dehydrogenase
anaplerotic rxns and examples
filling rxns that provide TCA intermediates. aa synthesis gives alpha ketoglutarate, FA [O] gives succinyl CoA, GLYCOLYSIS GIVES OXALOACETATE (FROM PYRUVATE VIA PYRUVATE CARBOXYLASE)
pyruvate dehydrogenase. pos vs neg mod
converts pyru to acetyl CoA. high pyru/CoA/NAD+ vs high malate/acetyl CoA/NADH or low oxalo –> pyru becomes oxalo via pyruvate carboxylase instead
Describe ETC. Is it endergonic or exergonic?
NADH goes thru complex I and FADH2 goes thru complex II —> Coenzyme Q/ubiquinone (small, hydrophobic –> moves freely in inner mito membrane) —> complex III —> cytochrome c (sticks out in matrix side) —> complex IV —> O2 = last e- acceptor —> becomes water. Energy released from moving b/w complexes drives H+ from matrix to intermembrane space; ATP synthase uses H+ gradient (moving from intermembrane space to matrix) to make ATP from ADP+Pi => [O] phosphorylation
Exergonic
Complex I of ETC
Site where NADH goes and = oxidized by NADH dehydrogenase. 4 p+ = pumped from matrix to intermembrane space
Complex II of ETC
Site where FADH2 goes and = oxidized by succinate dehydrogenase. DOESN’T PUMP p+/H+ or from other flavoproteins
Why is O2 mandatory for ETC?
O2 needs to be final e- acceptor to become water and not have ROS
ATP synthase mechanism
F0 = proton channel embedded in membrane, F1 = spinning headpiece that sticks into matrix. 3 catalytic sites (alpha/beta pairs): 1 empty, 1 ADP + Pi, 1 ATP. gamma subunit punches out ATP and spins to punch next site of ATP
How many p+ needed to make 1 ATP molec?
4p+: 3 to make ATP + 1 to bring PPi to drive ATP synthesis. ATP and ADP undergo passive exchange across the inner mitochondrial membrane
what are uncouplers for ATP synthesis?
ATP synthesis needs INTACT inner mito membrane w/ INTACT H+ grad. if H+ leaks into the matrix –> uncouples ETC (which makes H+ grad) from ATP synthesis (which uses H+ grad) –> energy converts to heat instead of ATP
beta [O] in muscle and liver vs liver
beta [O] = used to make ATP –> energy vs beta [O] = used to convert acetyl CoA to ketone bodies –> ketone bodies = used by muscle, kidney, brain/nervous tissue (not liver b/c it has no enzyme, not RBC b/c no mito) for energy
Describe the carnitine shuttle for FA [O]
1) acyl CoA synthetase uses ATP to react FA with CoA –> acyl CoA
2) carnitine palmitoyl transferase I attaches carnitine to acyl CoA => acyl carnitine; this is the rate limiting step, malonyl CoA inhibits CPT I
3) acyl carnitine diffuse from cyto to IMM
4) acyl carnitine translocase guides acyl carnitine from intermembrane space to matrix
5) carnitine palmitoyl transferase II kicks out carnitine and attaches CoA back to FA –> acyl CoA
6) acyl CoA undergoes beta [O]
main products of FA [O]. how much ATP is made per 16C FA [O]?
FADH2, NADH, acetyl CoA. 100 ATP
does amount of ATP inc or dec for unsat FA [O]?
dec b/c diff requirements for NADH/FADH2 prod
what are the main regulators of FA [O]?
inc ATP –> dec ETC –> inc NADH and FADH2 –> dec FA [O]
propionyl CoA
3C molec remains after beta [O] of odd chain FA –> converts to succinyl CoA for TCA cycle
What are the two ketone bodies produced by the liver? What metabolic condition in the liver favors formation of ketone bodies? What is a major difference between these two molecules and why is one more “stable” in the blood than the other?
beta-hydroxybutyrate and acetoacetate. you make ketone bodies b/c low glu/high glucagon/fasting/starving/high FA/high NADH/high acetyl CoA. humans favor beta-hydroxybutyrate b/c acetoacetate spont becomes acetone which is unstable
how many p+ pumped by complex I vs III vs IV vs ATP synthase?
4 (to IMM) vs 4 (to IMM) vs 2 (to IMM) vs 3 (to matrix)
substrate cycle vs chemically coupled rxns
Degradative and synthetic pathways for biomolecules that share enzymes but are controlled by separate regulatory enzymes, which themselves are reciprocally regulated vs two reactions occur simultaneously within the active site of the enzyme and one reaction will not happen unless the other reaction also occurs
