Biochem: Hemoglobin and O2 binding Flashcards
What is the structure of Haemoglobin?
Haemoglobin is a heterodimer that is comprised of 2 alpha and 2 beta subunits tied in a-b pairs. each subunit contains a Fe atom with a heme group that can bond atmospheric oxygen.
earn O2 binds to HG, the latter changes its conformation from tense to relaxed.
What factors affect the affinity of haemoglobin to O2?
the binding curve of HG and O2 is sigmoid, and is different from the binding curve of a simple myoglobin (a single monomer O2 binding molecule that is present in muscle cells). Since HG is an allosteric, homo- and heterotrophic protein, the affinity of HG to O2 depends on temperature pH and other allosteric factors as well as its ligand (O2). protons that bind allosterically to HG decrease the affinity to O2, so that the lower pH in body tissue (that is not the lungs) promote the release of the binding between HG and O2 molecules. CO and O2 increase HG affinity to them, which explains the high affinity of HG for O2 in the lungs. CO2, temperature and 2,3 BPG also affect the affinity.
What is the role of 2,3 BPG in HG affinity
An allosteric factor. 2,3 BPG binds allosterically to HG and stabilise it in its tense form. when bound to HG, it decreases the affinity to O2. 2,3 BPG is synthesised when there is a notable lack of oxygen, to make sure that HG doesn’t bind the available O2 molecules.
What is happening in CO poisoning and why can it lead to death?
CO has a 250 fold higher affinity to HG than O2. In a case of high CO concentration CO binds to HG at the same site as O2 and because of the high affinity, it outperforms O2, which leads to an extreme lack of O2 in tissue and death.
Where and when would you expect high activity levels of the enzyme glucose-6-phospatase?
Glucose-6-phosphatase catalyses dephosphorylation of glucose-6-phosphate to generate glucose for the glycolysis. Therefore we would expect it in high levels in the liver after physical exercise
Where does FA-synthesis take place?
in the cytoplasm (and in SR)
What are the reactants and products of the FA-synthesis process?
reactants:
1 acetyl CoA
7 Malonyl CoA
14 NADPH
14 H+
Products:
7 CO2
8 CoA
14 NADP+
6 H2O
what are the 4 main steps of FA synthesis in the cytoplasm?
- Condensation: specifically decarboxylating Claisen condensation, which is important for forming carbon-carbon bonds, and the fatty acid chain. In this process Acetyl CoA and Malonyl CoA are condensed together to form aceto-acetyl. It uses acetyl CoA as the nucleophile and Malonyl CoA as the electrophile
- Reduction: Acetoacetyl is reduces using NADPH
- Dehydration: Water is removed from the alcohol group, creating a double bond
- Reduction: (second reduction) The double bond is reduced to a single bond, using NADPH, completing the cycle and forming a saturated fatty acid chain.
What is the advantage of storing energy as glycogen over glucose?
free glucose absorbs a lot of water, thereby can change the concentration gradient in the cell, whereas glycogen absorbs very little so it has negligible influence over the cell.
Who are the key players in glycogen synthesis?
- Glycogenin - the initiator of glycogen synthesis. this enzyme receives UDP-glucose molecules Andy binding Mn++ builds the initial (short) chain of glycogen by linking them together via tyrosine residue.
- UDP-glucose - produced by UDP-glucose-phosphorylphosphorylase which catalyses the linkage of G1P to UTP while releasing pyrophosphate. in UDP-glucose, 1 phosphate comes from G1P and 1 P remains from UTP. during glycogen synthesis UDP is released from the glucose which makes the process energetically favourable
- G1P - released during glycogen breakdown, and also is used to synthesise UDP glucose.
structure of the heme group in haemoglobin
protoporphyrin, to which is bound a single iron atom in its ferrous (Fe2+) state. The iron atom has six coordination bonds, four to nitrogen atoms that are part of the flat porphyrin ring system and two perpendicular to the porphyrin that can bind O2.
In certain parts of Africa, the frequency of sickle cell anaemia is very high. what is the reason for this?
Sicle cell anemai is a disease that is caused by a single gene mutation encoding an AA in the beta subunit of HG. Studies revealed that both parents should carry a copy of the mutated allele in order to have an offspring with SCA. In Aft=rica, the heterozygous allele became dominant as it forms a certain resistance to malaria. to fight off malaria, the most common variant of this gene is the heterozygous one and therefore there are more people who have SCA.
