Biochemistry Part 6 Flashcards
How is redox balance maintained?
Only limited amounts of NAD are present in a cell
Glycolysis reduced NAD+ to NADH and +
NADH must be re-oxidised to let glycolysis continue
NAD+ is regenerated through the oxidative metabolism of pyruvate
What are the three stages of oxidation of pyruvate?
- Acetyl-CoA production
(Citric acid cycle) - Acetyl-CoA oxidation
(Krebs cycle) - Electron transfer and oxidative phosphorylation
(TCA cycle)
What is the roll of NADH?
Delivers electrons to the respiratory chain
Where does the TCA cycle occur?
In the mitochondrial matrix
How does pyruvate enter the mitochondrial matrix?
H+ gradient from cytosol to matrix
Pyruvate transporterL H+/pyruvate symport by facilitated diffusion
How is pyruvate metabolised to Acetyl-CoA in the matrix?
Pyruvate dehydrogenase complex catalyses decarboxylation of pyruvate to acetyl-CoA
What does PDC consist of?
3 enzymes
How is PDC regulated?
allosterically regulated by phosphorylation
What does PDC determine?
Glucose oxidation in well oxygenated tissues
Is the metabolism of pyruvate reversible?
No
What are the three enzymes involved in PDC?
Pyruvate dehydrogenase
Dihydrolipoyl transacetylase
Dihydrolipoyl Dehydrogenase
What are the four reactions of PDC?
- Pyruvate loses CO2 and HETPP is formed
- Hydroxyethyl group is transferred to lipoic acid and oxidised to form acetyl dihydrolipoamide
- Acetyl group is transferred to CoA
- Dihydrlipoamide is deoxidised
How many reactions are involved in the TCA cycle?
Eight
What happens to the two-carbon unit from acetyl-coa?
Condenses with a four-carbon unit; resulting six-carbon unit is decarboxylates twice (yields CO2)
How many oxidation reactions are involved in the tea cycle?
Four
- yield NADH + H+ and FADH2
- one GTP is formed
Where are all enzymes of the TCA cycle located?
In the mitochondrial matrix apart from succinate dehydrogenase
Where is succinate dehydrogenase located?
Inner mitochondrial membrane
What do all products of stage II metabolism give rise to?
Acetyl-CoA and as a result can be oxidised completely to CO2 via the CO2 cycle
What does each turn of the TCA cycle involve?
- uptake of two carbon atoms as acetyl-CoA and the release of two carbon atoms as CO2
- Transfer three pairs of electrons to NAD+ to form NADH + H+ and one pair of electrons to reduce FAD to FADH2
- One substrate level phosphorylation reaction results in the formation of GTP from GDP and Pi
What does high ATP, NADH and acetyl-CoA means…
Plenty of energy
What does high ADP and NAD+ means…
Lack of energy
What does high succinyl-CoA and acetyl-CoA and acetyl-CoA mean?
Plenty of precursor molecules for biosynthetic reactions
What is PDC deficiency?
Stage II metabolic disorder
-gene located on C chromosome
How does PDC deficiency present?
Largely as neurological disease in children
- respiratory problems
- persistent lactic acidosis
- retardation and seizures
- poor muscle tone (hypotonia) and lack of coordination
What is HLRCC?
Hereditary leiomymatosis and renal cell cancer
-defect in fumarate hydrates
How does HLRCC present?
Multiple systemic benign and malignant tumours
- kidney particular ice of malignant metastasis
- link between TCA cycle and cell proliferation
