Week 4 Flashcards
What is the pentose phosphate pathway?
A metabolic pathway parallel to glycolysis. It generates NADPH and pentoses as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides
How is pyruvate formed under anaerobic conditions reduced to lactate?
With electrons from NADH, recycling NADH to NAD+ and allowing continued glycolysis in the process of lactate or alcohol fermentation
What is the major catabolic fate of glucose-6-phosphate?
Glycolytic breakdown to pyruvate
What makes the pentose phosphate pathway different?
- There is glucose oxidation without ATP production
- oxidation is achieved by dehydrogenation using NADP+, not NAD+
Is the primary role of the pentose phosphate pathway catabolic or anabolic?
Anabolic
Where does the pentose phosphate pathway operate?
Like glycolysis, it occurs in cell cytosol.
- in rapidly dividing cells (bone marrow, skin, tumour cells) it uses the pentose ribose-5-phosphate to make RNA, DNA, ATP, NADH, FADH2, coenzyme A
- in tissues involved in cholesterol and fatty acid synthesis (liver, adipose tissue, adrenal gland)
What are the two steps of pentose-phosphate pathway?
- Oxidative (irreversible)- oxidation of glucose: 3 molecules of glucose-6 phosphate give rise to 3 molecules of CO2 and 3 molecules of 5-carbon sugars
- Non oxidative (reversible)- in tissues that require primary NADPH, the pentose-phosphate produced in oxidative phase are recycled glucose-6 phosphate. Regenerates 2 molecules of glucose-6 phosphate and 1 molecule of the glyceraldehyde 3-phosphate
What is the first reaction of pentose phosphate pathway
Oxidation of glucose 6-phosphate generating first molecule of NADPH
What does the non-oxidative phase recycle?
Pentose phosphates to glucose-6 phosphates
What is transketolase?
A thiamin pyrophosphate (TTP) dependent enzyme. TTP is a cofactor also known as vitamin B1
What does the ring of TTP stabilise?
The carbanoin in the dihydroxyethyl group carried by transketolase
When is the pentose phosphate cycle complete?
When six pentose phosphates have been converted to five hexose phosphates
Why is pentose phosphate pathway especially important in red blood cells? (erythrocytes)
- Mature erythrocytes do not divide, so there is no need for ribose-5-phosphate to be used for nucleic acid synthesis
- Erythrocytes do need a supply of NADPH in order to protect the cell membrane from oxidative damage
- Because the production of NADPH offers a protective mechanism for the reduction of glutathione
- Glutathione is a thiol compound which main function is to maintain a reducing environment in the cells by virtue of its -SH group
What is ribose-5-phosphate?
A precursor for nucleotide and nucleic acid synthesis
What is oxygen?
The element (O) exists in the air as a diatomic molecule O2, it is a toxic mutagenic gas
What is hypoxia?
Changes in supply or demand of o2 can lead to insufficient blood perfusion (ischaemia) and insufficient cellular o2 (hypoxia)
-inadequate o2- insufficient ATP, cellular dysfunction or death
What are reactive oxygen species?
Oxygen-containing molecules
How are ROS formed?
By redox reactions, electronic excitation or enzymes
What are the two species of ROS?
- Free radical (at least one unpaired electron) - eg superoxide
- Non-radical
What is oxidative stress?
Overproduction of ROS within the cell
How are ROS produced by enzymes?
ROS may be produced by several enzymes as the primary function eg NADPH oxidase or as a secondary byproduct eg mitochondrial ETC
What is oxidative eustress?
- Eustress is a state of low-level H2O2 maintenance that is associated with physiological redox signalling
- Eustress leads to reversible oxidation of cysteine thiols
- This alters protein structure, activity, localisation
- Can occur through methionine oxidation
What is oxidative distress?
- A state of supra-physiological concentration of H2O2 leading to unspecific oxidation of proteins
- This results in altered responses, reversible and irreversible damage to biomolecules causing growth arrest and cell death
- Causes damage to all classes of macromolecules, impairing their function
- products of this damage can cause issues
What are disulfide bonds?
Covalent bonds between two sulfur atoms formed by the coupling of two thiol groups
