Principles of Biochemistry 13 |Glycolysis in Red Blood Cell| Class Notes |HarvardX

Red Blood Cell

© Philip W Kuchel, et al.

Physiological Adaptation of RBC:

• one third of the volume is occupied by hemoglobin.
• lack of intercellular organelles, like Mitochondrial
• allows deformation for moving through narrow capillaries
• lactate fermentation
• Cori cycle: lactate catabolism

Cori Cycle

Rapoport-Luebering shunt

It is a pathway that converts 1, 3-bisphosphoglycerate, one intermediate of glycolysis, into its isomer, 2,3-BPG.

As a bypass pathway, the ATP generation was avoid. As a result, most cells have a very low lever of the 2,3-BPG. But it is very high in RBC since this molecule has a very important function in release of Oxygen.

NADH was produced in Glycolysis works for maintaining the iron in Fe²⁺ state, which was used to carry the Oxygen.

NADH maintains reduced iron

HMP shut

HMP shut could protect RBC from reactive oxygen species.
Defense against ROS

Oxygen Tranportaion

Conformation Chage:

• R-State (oxygenated, high affinity)
• T-State (non-oxygenated, low affinity)

Affinity

Cooperative binding: Dynamic Oxygen biding

• Releasing about 25% of oxygen
• When it is needed, it could releasing 75% of O₂

$$
Hb \underset{O_ 2}{\overset{K1}{\rightleftharpoons}}
HbO_ 2 \underset{O_ 2}{\overset{K2}{\rightleftharpoons}}
Hb(O_ 2)_ 2 \underset{O_ 2}{\overset{K3}{\rightleftharpoons}}
Hb(O_ 2)_ 3 \underset{O_ 2}{\overset{K4}{\rightleftharpoons}}
Hb(O_ 2)_ 4
$$

© HarvardX

Binding affinity change

• Leftward shift: higher affinity
• Rightward shift: lower affinity

PH

The PH changed, which also connected the change of concentration’s level of
CO₂:

Muscle: CO₃, reducing the PH, which causing Rightward shift, and decreasing the affinity, increasing the releasing of the O₂
Lungs: CO₃ reduced, PH increased.

2,3-BPG

In the T-shape it was bond
In the R-shape, the bond was crushed and 2.3-BPG was released.

digraph{ rankdir = "UD" node [shape = box ] Lactates1 [label ="Lactate *2"] Lactates2 [label ="Lactate *2"] ATP [shape = "none"; fontcolor = "white"] ATP6 [label = "ATP *6"; shape = "none"; fontcolor = "white"] Glucose [label = "Glucose", shape ="hexagon", height = 1] Glucose2 [label = "Glucose", shape ="hexagon", height = 1] mm1 [label = "" , shape = none, height = 0, width = 0] mm2 [label = "" , shape = none, height = 0, width = 0] mm3 [label = "" , shape = none, height = 0, width = 0] mm4 [label = "" , shape = none, height = 0, width = 0] Lactates1 -> Lactates2 [label = "transport"; style ="dashed"] Lactates2 -> mm2 [arrowhead = none; headport="n"] mm2 -> Glucose2 subgraph cluster_1{ label = "Red Blood Cell" style = "filled" color = "crimson" fontsize = 20 Glucose; mm1; {rank=same; Glucose; Lactates1; mm1} Glucose->mm1 [dir = none] mm1 -> Lactates1 mm1 -> ATP } subgraph cluster_2{ label = "Liver" style = "filled" color = "deeppink4" fontsize = 20 Glucose2; Lactates2 ATP6 -> mm2 } }digraph{ ATP3 [label="ATP", color="salmon", style="filled"] ADP3 [label="ADP"] BSG [label = "1,3-\nBisphosphoglycerate", shape = underline] Phos [label = "3-Phosphoglycerate", shape = underline] BPG [label = "2,3 - BPG", shape = "box"] mm7 [label = "Phosphoglycerate\nkinase" , shape = box, color = "coral", fontcolor = "coral"] BSG -> mm7 [dir = back, color = "deeppink"] mm7 -> Phos [color = "deeppink"] BSG -> BPG [label ="mutase", dir=both, color = "red"] BPG -> Phos [label = "Rapoport-\nLeubering shunt", color = "red", tailport ="s"] {rank="same"; BSG; BPG} subgraph BB{ {rank = same; ADP3; mm7} {rank = same; ATP3; Phos} ADP3 -> mm7 [arrowhead =none, headport = "s"; color = "blue"] mm7 -> ATP3 [tailport = "s"; color = "blue"] } }digraph{ rankdir = "LR" mm1 [label = "" , shape = none, height = 0, width = 0] mm2 [label = "" , shape = none, height = 0, width = 0] mm3 [label = "" , shape = none, height = 0, width = 0] Fe [ label = "<f1> Fe(3+)-Hb |<f2>|<f3> Fe(2+)-Hb" shape = "record" color = "white" ]; cytochrome [ label = "<f1> Reduced\ncytochrome b5 |<f2>|<f3> Oxidized\ncytochrome b5" shape = "record" color = "white" ]; NAD [ label = "<f1> NAD+ |<f2>|<f3> NADH" shape = "record" color = "white" ]; Glu [ label = "<f1> Glyceraldehyde\n-3-P |<f2>|<f3>1,3-\nbisphosphoglycerate" shape = "record" color = "none" ]; Fe:f1 -> mm1 [arrowhead = none, headport ="N", color = "red"] Fe:f3 -> mm1 [dir = "back", headport ="s", color = "red"] mm1 -> cytochrome:f1 [arrowhead = none, tailport ="N"] mm1 -> cytochrome:f3 [tailport ="s"] cytochrome:f3 -> mm2 [arrowhead = none, headport ="s", color = "red"] cytochrome:f1 -> mm2 [dir = "back", headport ="n", color = "red"] mm2 -> NAD:f1 [tailport ="n"] mm2 -> NAD:f3 [arrowhead = none, tailport ="s"] NAD:f1 -> mm3 [arrowhead = none, headport ="n", color = "red"] NAD:f3 -> mm3 [dir = "back", headport ="s", color = "red"] mm3 -> Glu:f1 [tailport ="n"] mm3 -> Glu:f3 [tailport ="s"] subgraph cluster_1{ Glu label = "Glucose Glycolysis" style = "filled" color = "aquamarine2" fontcolor = "salmon" fontsize = 20 } }digraph{ subgraph cluster_1{ hexo2 [label = "", shape = hexagon, width = 1, height = .8] node [style=filled,color=white]; label = "Glucose-6-phosphate"; URL="https://www.bing.com"; subgraph C{ rank = same P1 -> hexo2 [dir = none, headport = "nw", arrowhead ="none"] } color = "white"; labeljust=l labelloc=b } subgraph cluster_2{ hexo3 [label = "", shape = hexagon, width = 1, height = .8] node [style=filled,color=white]; label = "Fructose-6-phosphate"; URL="https://www.bing.com"; subgraph C{ rank = same P2 -> hexo3 [dir = none, headport = "nw", arrowhead ="none"] } color = "white"; labeljust=l labelloc=b } subgraph cluster_3{ hexo4 [label = "", shape = hexagon, width = 1, height = .8] node [style=filled,color=white]; label = "Fructose-1,6-phosphate"; URL="https://www.bing.com"; subgraph C{ rank = same P3 -> hexo4 [dir = none, headport = "nw", arrowhead ="none"] hexo4 -> P4 [dir = none, arrowhead ="none"] } color = "white"; labeljust=l labelloc=b } mm2 [label = "Phosphoglucose\nisomerase" , shape = box, color = "coral", fontcolor = "coral"] mm3 [label = "Phospho\nFructokinase" , shape = box, color = "coral", fontcolor = "coral"] mm4 [label = "Aldolase" , shape = none, color = "coral", fontcolor = "coral"] mm5 [label = "Triose\nphosphate\nisomerase" , shape = box, color = "coral"] mm6 [label = "" , shape = none, height = 0, width = 0] mm7 [label = "" , shape = none, height = 0, width = 0] P1 [label="", shape = circle, color= "cyan3", height = 0.3, width = 0.3] P2 [label="", shape = circle, color= "cyan3", height = 0.3, width = 0.3] P3 [label="", shape = circle, color= "cyan3", height = 0.3, width = 0.3] P4 [label="", shape = circle, color= "cyan3", height = 0.3, width = 0.3] hexo2 -> mm2 [dir = none , color = "deeppink"] mm2 -> hexo3 [ color = "deeppink"] hexo3 -> mm3 [dir = none , color = "deeppink"] mm3 -> hexo4 [ color = "deeppink"] hexo4 -> mm4 [dir = none , color = "deeppink"] mm4 -> GAP [color = "deeppink"] DHAP -> mm4 [dir = back , color = "deeppink"] DHAP -> mm5 [dir = back , color = "deeppink", headport = w] mm5 -> GAP [color = "deeppink", tailport = e] hexo2 -> mm6 [headport = "w"; dir = none] mm6 -> mm7 [dir = none] HMP -> hexo3 [headport = "w"; color ="red"] HMP -> DHAP [headport = "w"; color ="red"] subgraph C{ rank = same mm4 DHAP [label= "Dihydroxyacetone\nphosphate", shape = underline] GAP [label= "Glyceraldehyde\n3-phosphate", shape = underline] } subgraph cluster_4{ node [shape = none] NADP [label ="NADP+"] Red [label = "Reduced\nglutathione"] Oxi [label = "Oxidized\nglutathione"] DeROS [label = "Destroyed\nROS"] mm8 [label = "" , shape = none, height = 0, width = 0] mm9 [label = "" , shape = none, height = 0, width = 0] mm7 -> HMP {rank = "same"; mm6; mm7; HMP} NADP -> mm7 [dir = none, headport = "e"; color="red"] mm7 -> NADPH [tailport = "w"; color="red"] NADPH -> mm8 [dir = none, headport = "w"] mm8 -> NADP [tailport = "e", color="black"] {rank = "same"; NADP; NADPH} Oxi -> mm8 [dir = none, headport = "e"; color="red"] mm8 -> Red [tailport = "w"; color="red"] Red -> mm9 [dir = none, headport = "w"] mm9 -> Oxi [tailport = "e", color="black"] {rank = "same"; Oxi; Red} ROS -> mm9 [dir = none, headport = "e"; color="red"] mm9 -> DeROS [tailport = "w"; color="Red"] {rank = "same"; ROS; DeROS} label = "HMP shut:\ndefense\nagainst ROS" fontcolor = "white" fontsize = 20 style = "filled" color = "darksalmon" labeljust= "l" } }