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

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

}

}

Rapoport-Luebering shunt

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

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”]
}

}

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

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 = “ Fe(3+)-Hb || Fe(2+)-Hb”
shape = “record”
color = “white”
];
cytochrome [ label = “ Reduced\ncytochrome b5 || Oxidized\ncytochrome b5”
shape = “record”
color = “white”
];

NAD [ label = “ NAD+ || NADH”
shape = “record”
color = “white”
];

Glu [ label = “ Glyceraldehyde\n-3-P ||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
}

}

HMP shut

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

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"

}

}

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.