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L2 Blood Transport (Lipoprot
Floats around in plasm
LP complexes carry…
L2 Blood Transport
Lipoprot
- Floats around in plasm
- LP complexes carry lipids thru circ
- Distribution & redis thruout body
~ formed in the gut
~ rake it to muscle, take it to adipose tissue, and go to liver
- Composition: apoLP (apoprots), phopholipids, triglycerides, cholesterol, cholesteryl esters
- looks like a (C)→ has a cargo inside
3 Classes of LP
- Chylomicrons (CMs) [live for ~30mins]
~ Prod in gut: loaded w/ dietary lipids
~ Distribute lipids to rest of body
~ Taken up by liver (as CMRs) =remnants
- Low density LPs (LDLs)
~ Prod in liver (VLDL)= very LDL for recirculating fats then into LDL
~ Loaded w/ liver lipids
~ Dist. lipids to rest of body
~ Taken up by liver
- High density LPs (HDLs)
~ Prod in liver- but empty!
~ Pick up cholesterol/pilids from rest of body → dump in liver
~ opp of LDL
LP unloading
- 2 ways to remove lipids from bld
- Endocytosis of LP complex (liver, mostly) → remove the whole LP from bld
~ reqs LPRs [has to be present on whatever organ that is taking up the LP, ∴ your liver is packed w/ LP
- Ezm-catalysed removal of lipids (FFAs) from LPs
~ Reqs LP lipase ezm (LPL)
- LPL ezm
~ FOund on muscle, adipose tissue, heart, mammary glands
~ Liberates FFAs from TGs, FFAs are then removed from LPs
Apolipoprots (apoprots)
- Dictate the fate of LPs
~Ligands fro (C)-surface Rs (destination)
↳ apoB100 & apoE → req for (C)ullar uptake of LDLs
↳ apoA-I → req for (c)ullar uptake of HDLs
~ Ezm cofactors (regulate act. )
↳ apoCII → req for unloading FAs (LPL- cofactor)
- Apoprot cofactors are recycled between circulating LPs (they literally play swapsies)
LP lipase
- takes our TG and chops them up into FAs + glycerol so we can dist them
LP removal Rs
- Mediated endocytosis
- When the liver takes up the LDLs and CMRs
Other transports
Lipid transport
- absorbing lipids in intestines
- Metabolising lipids in liver
- Burning and storing lipids in adipose & muscle
- CMR: after CM has unloaded its fats
- IDL: intermediate
- Reverse cholesterol transport
Gas transport
- Gas exchange via passive diffu
- Always ⬇︎ a conc grad
- Lungs = ↑O2, ↓CO2 (O2 will enter bld, CO2 will leave bld)
- Tissues = ↓O2, ↑ CO2 (O2 will leave bld, CO2 will enter bld)
- diff curves
Hb
- O2 solubility in plasma is not enough to support life (Max ~3mL/L)
~ ∴ need a BP to ⇈O2 transport ⇒ Hb
- Prod by maturing RBCs
- 4 subunits each consisting of
~ Globin (polypept) chains
~ HbA: 2x α-globin & 2x 𝛽-globin
~ Haem unit (1x Fe2+ & 1x protophophyrin molec)
- O2 binds loosely & reversibly to Fe2+ of Hb: co-ordination bonds
Hb Rules OK
- O2 transport:
~ O2 binds reversibly to haem (Hb) in RBC
~ 1g Hb can bind 1.39mL O2 [massively ⇈s the O2 binding capacity of bld]
↳ ♂ [Hb] 150g/L = 208.5mL/L of O2 (70x plasma [O2])
- Loading & unloading of O2 is still entirely passive
~ Dependent upon [O2] grad
O2 Dissociation curve
- Amt of O2 loaded depends on [O2]
- Hb saturates easily- only 20-25% O2 unloaded in tissues
- Local conditions alter how tightly Hb binds O2
- Hb dumps more O2 in metabollically- active tissues
~ Acidosis, ⇈temp, ⇈PCO2 (Bohr effect)
CO2
- much more sol (~22x) in plasma/cytoplasm than O2
- But, we can ⇈ transport eff if we load it into RBCs
- CO2 transport
~ Carbonic anhydrase in RBC catalyses the reaction [catalyses the first arrow]
~ Hb in RBC (and prots in plasma) binds CO2 forming carbamino compounds
CO2 transport
- Dissolved CO2 (~10%)
~ ~20x more sol than O2- sig fraction of total transport
- Carbamino (~20%)
~ CO2 combines w/ terminal amino grps of prot (Hb)
~ R-NH + CO2 ⟷ R-NHCOO- + H+
~ CO2 & O2 bind separate pairs of Hb
- Bicarbonate (~70%)
~ Most Co2 in bld carried as bicarbonate
~ CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-
- Slow in plasma, 5000x faster in RBC (contain carbonic anhydrase)
- Diffuse (facilitated) out of RBCs (Cl- shift → more Cl- in venous bld)
-
Bld
- Fluid in bldvs & chambers of heart
- 6-8% of body mass ie 60-80mL/kg
- A 70kg person has ~5L of bld
- 55% fluid (plasma) & 45% (C)s (RBC [pcked w/ Hb], WBC & platelets) in a healthy male
(C)s of Bld
- RBC: eryhtrocytes, no nuc, packed full of prots & salts
- WBC: leukocytes, named 'white' bc its just not red (not actually white in clr if stained)
- Platelets
Erythrocytes
- Biconcave disc: 7-8µm diameter, 2µm
- Consists of memb enclosing
~ H2O, electrolytes, Hb (⇈s O2 cap of bld), metabolic ezms (inc carbnic anhydrase [takes gaseous CO2 & converts it to iron...]
- No nuc or organelles
Plasma
- Straw coloured fluid [yellow, bc metabolised that is in..?]
- Made up of
~ H2O (~90% by mass)
~ Plasma prots (7%)
~ Salts (Na+, Cl-), buffers (HCO3-)
~ Nutrients (eg. Glucose monosacs, aa)
~ Wastes (eg. urea, uric acid, biliurin- breakdown product from Hb)
~ Dissolved gases (eg. O2, CO2)
- Rapid transport syst: nutrients, watses, hormones, heat
Transport: depends on the solubility [hphilic → hphobic]
- Ions (salts)- v soluble, dissolved (exc. FE3+ : this is the form that we transport in bld & it's not sol at all, precipitates)
- Sugars (monos) v sol, dissolved
- Gases- variably sol, dissolved, complexed or bound
- Hormones: variably sol, dissolved, complexed or bound [ depends on the st of the hormones, some cholesterol- lipid)]
- Lipids: insol, bound [fats, TG, phosphates]
Carriers
- Moves all the transported things around
- Binding prots & friends [normally amphipathic]
~ Prod by liver, bone marrow [Hb prod here] or intestines
- May be simple, non-spec: albumin [dom prot present in plasma, picks up everything Ca, vits, etc]
- Complex & not v spec: LP
- Or complex & v spec: Hb (spec for O2), hormone-/vit-binding prots (usually spec to one hormone or one vit), transferrin (transport iron)
Albumin
- Main prots of plasma (>~50%)
- Big (66.5kDa) glob prot (ave prot is 50kDa)
- Prod (+ exocytosed) by liver
- Reversibly binds just abt everything [can be released when necessary]
~ Cations, FFAs, vits, hormones, bilirubin etc
~ Varying ectents [won't bind all (diff %s) bc weak bonds, most thins are bound by multiple carriers]
Hormones (2 forms: H2O sol or lipid sol)
- Many are H2O sol
~ Adrenaline, dopamine, DA, insulin, glucagon, FSH, LH, TSH, ANP, S, CCK etc
- Other carriers
~ All steroids (cholesterol- derivs = lipids) [doesn't float around in bld]
↳ Oestrogen/Proges/testos → sex-hormone-binding globulin (SHBG)
↳ Cortisol/ aldosterone: moved around by prots called transcortin
~ TH: Thyroid hormone-binding globulin (TBG)
Vits
- Bs & C- H2O sol, dissolved in plasma
- A,D,E,K all lipid sol- need a carrier
~ Carried by binding prots produced in the liver/intestines
↳ A: retinol binding prot & LP
↳ D: VDBP (LP if dietary source)
↳ E: LP, albumins
↳ K: LP
Learning Outcomes
- List the diff componenents of bld
- Outline the mechs & molecs used for transport of bld-borne diseases
- Describe the diff classes of LP
- Outline LP metabolism & the function of apoprots
- Describe the st&f of Hb
- Understand the Hb-O2 dissociation curve
- OUtline CO2 transport