Myoglobin and Hemoglobin Flashcards
majority of cell proteins, soluble in water
globular proteins
Hydrogen bonding acts to _________ the highly polar N-H bonds and C=O of the secondary structure
neutralize
Globular protein structure is stabilized by what three things?
Hydrogen bonds, ionic interactions, and disulfide bonds (least common)
What are some functions of globular proteins?
storage of ions (myoglobin which stores the majority of the body’s iron in ferritin), transport (hemoglobin and oxygen), antibodies, muscle contraction (actin/myosin), enzymes
T/F. Ligands or globular proteins are held irreversibly.
False
If a protein has multiple subunits, and a ligand binds leading to a conformational change in the other subunits, this is _______________.
cooperativity (can be positive or negative)
What quality of proteins make myoglobin and hemoglobin unique?
Unlike other protein side chains which lack an affinity for oxygen, myoglobin and hemoglobin evolved to contain organometallic compounds that can carry oxygen
What makes iron suitable for oxygen carrying?
Easily oxidized but doesn’t form free radicals like other transition metals
What is the purpose of having a globular protein surround the heme?
The protein protects the iron from becoming oxidized early
How do myoglobin and hemoglobin compare in relation to oxygen binding affinity?
Myoglobin binds oxygen with higher affinity so even at low pO2 levels
Although myoglobin and hemoglobin have similar functions, their ______ _______ are completely different.
primary structures
What is the missense mutation that leads to sickle cell anemia?
E6V
Mutation of glutamate to valine at the sixth amino acid position
Protoporphyrin IX containing a bound iron atom is called a _____.
heme
With oxygen binding, does the iron shift closer to the proximal or distal His?
proximal
The _____ His forms a coordination complex with the iron.
proximal
Why are there hydrophobic amino acids (Val and Phe) surround the heme group?
Prevent polar molecules from entering and oxidizing the Fe
- What are the two states hemoglobin can be found in?
2. Which state forms in low pH and why?
- T and R state
- T state forms in low pH. High concentration of hydrogen ions leads to the protonation of the His 1446 at the C term of beta. The His-H forms a salt bridge with an Asp 94 residue. This makes the hemoglobin have a lower oxygen affinity.
Salt bridges and 2,3- BPG stabilize _____ state.
T
Positive cooperativity is recognized by a ______ binding curve when graphed.
sigmoidal
What can you add to patient blood to encourage release of oxygen?
2,3- BPG
How does the pH difference between the lungs and the tissues make oxygen transport more effective?
Tissues have lower pH because actively metabolizing tissues releasing hydrogens and carbon dioxide. Lungs have higher pH. In lungs, the R state is more common allowing Hb to pick up oxygen. Once Hb travels throughout the body, comes into contact with acidic tissues. Protonation of His occurs, forcing Hb into T state and leading to dropping off oxygen.
How does 2,3- BPG stabilize the T state?
binds to positive residues in Hb
CO wants to bond as a triple bond, but the ________ histidine group blocks the linear fashion in the pocket
E7
Heme can also bind this molecule, which stimulates tissues to relax and blood to flow
nitric oxide
What is the enzyme found in placental cells and RBCs that helps convert 1,3-BPG (by product of glycolysis) to 2,3 BPG?
2,3 BPG mutase
Explanation: in RBCs, helps release oxygen for people in high altitudes. In placenta, helps release oxygen to baby from mother.
In tissues, Hb binds NO instead of one of the four oxygens. Why does this happen?
NO is a vascular smooth muscle relaxer. Allows for easier flow of oxygen into tissues.
EPAS1 up regulation is found in what populations?
Tibetans. Increased forearm blood flow compared to low altitude dwellers
Methemoglobin is Hb with _____ instead of ____. This reduces the ability to carry oxygen. Newborns that are given too much NO have a blue tinge because ____ binds ____ better than it binds oxygen.
Methemglobin is Hb with Fe 3+ instead of Fe 2+. This reduces the ability to carry oxygen. Newborns that are given too much NO have a blue tinge because Fe 3+ binds cyanide better than it binds oxygen.
Which enzyme can reverse the methemoglobin to hemoglobin? Deficiency of this enzyme can cause what?
NADH- methemoglobin reductase
cyanosis
NADH- methemoglobin reductase is found _____ less in newborns, making them extremely susceptible to methemoglobinemia.
50%
Methemoglobinemia can be caused by what things?
Deficiency in NADH- methemoglobin reductase, too much NO as infants, reactive oxygen species/inherited defects
Fetal hemoglobin, _________, has a stronger affinity for oxygen, and it extracts hemoglobin from the mothers blood
HbF
Why does HbF become useless postpartum?
The high oxygen affinity prevents release at tissues
What is HbA1c?
Glycated Hb
What creates the sickled appearance of RBCs in HbS?
E6V mutation leads to a compilation of hydrophobic valines on the outside of the protein. The Hb is “sticky” and hydrophobic regions group together, curving inward
T/F. Individuals with sickle cells should live at high altitudes
False. Increases sickling and they already have lower oxygen affinity
How is silencing BC11A a possible treatment for sickle cell?
Increase production of HbF
Hemoglobin C, changes E6K, and leads to what disease
mild hemolytic anemia
Explanation: mild because changing polar AA to polar AA.
