The catabolism of Pyruvate

Question 1

What steps does a cell take to maintain redox balance?

Answer 1

Only limited amounts of NAD+ are present in a cell as NAD+ is derived from niacin, a vitamin.
Glycolysis reduces NAD+ to NADH + H+.
NADH must be re-oxidised to let glycolysis continue.
NAD+ is regenerated through the oxidative metabolism of pyruvate.

Question 2

What delivers electrons to the respiratory chain?

Answer 2

NADH delivers electrons to the respiratory chain.

Question 3

What happens to NAD+ after the electron transport chain stage?

Answer 3

NAD+ is re-generated as an electron acceptor to maintain Stage 1 and Stage 2 metabolism.

Question 4

What are the different names for the second stage of respiration?

Answer 4

Citric Acid Cycle
Krebs Cycle
Tricarboxylic Acid (TCA) cycle.

Question 5

Where does the TCA cycle occur?

Answer 5

THE TCA cycle occurs in mitochondria.

The matrix contains enzymes of the TCA cycle.

Question 6

Where does the electron transport chain occur?

Answer 6

The inner membrane of the mitochondria contains proteins for electron transport chain, ATP synthase, and transport proteins.

Question 7

How are mitochondria thought to have developed?

Answer 7

Through a symbiotic relationship.

Question 8

How does pyruvate enter the mitochondrial matrix?

Answer 8

There is a H+ gradient form cytosol o matric. Pyruvate transporter: H+/pyruvate symport by facilitated diffusion.
A similar process regulates ADP, ATP and inorganic phosphate (Pi) movement into and out of mitochondria.
(There is a higher concentration of protons in the intermembrane space than the matrix
(Facilitated diffusion regulated the enter and exit of ATP).
(Symporter allows for facilitated diffusion).

Question 9

Once in the matrix, how is the pyruvate metabolised to Acetyl-CoA?

Answer 9

He pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA.
PDC consists of 3 enzymes and is allosterically regulated by phosphorylation.
PDC activity determines glucose oxidation in well oxygenated tissues.
The reaction is irreversible. Acetyl-CoA cannot be converted back to pyruvate.
(Once the pyruvate is turned into Acetyl-CoA, this cannot be reversed).

Question 10

What is a general way that you can identify important, irreversible steps in chemical processes in the human body?

Answer 10

Whenever you get release of CO2, you know this step is a big deal. THE reaction tends to be reversible because animal cannot attach CO2 to chemicals). This determines how much energy you are going to get because it is irreversible.

Question 11

Can you describe the kerb cycle?

Answer 11

8 reactions in total.
A 2-carbon unit (from acetyl-CoA) condenses with a 4-carbon unit.
The resulting 6-carbon unit is decarboxylated twice, yields CO2.
4 oxidation reactions, yield NADH + H+ and FADH2.
One GTP is formed, energy.
The 4-carbon unit is recreated.
(CoA gets recycled and Acetyl goes on. Acetyl coenzyme A is an activated form of carbon).
(The 6 carbon unit loses 2 carbons (as CO2) enough energy to form one GTP = ATP).
(2 carbons enter the cycle and 2 carbons exit the cycle, as CO2).

Question 12

All enzymes of the TCA cycle are located in the mitochondrial matrix, apart from what, which is located where?

Answer 12

Succinate dehydrogenase.
Succinate + FAD -> Fumarate + FADH2
It is integrate in the inner mitochondrial membrane.

Question 13

What does the TCA cycle have a central role in?

Answer 13

Catabolism

Question 14

What are the main features of the TCA cycle?

Answer 14

All products of stage II metabolism can give rise to Acetyl-CoA and as a result can be oxidised completely to CO2 via the TCA cycle.
All of the enzymes of the TCA cycle are associated with mitochondria except succinate dehydrogenase.
Each turn of the TCA cycle involves the uptake of 2 carbon atoms in the form of acetyl-CoA and the release of 2 carbon atoms as CO2.
Each turn of the cycle results in the transfer of 3 pairs of electrons to NAD+ to form NADH + H+, and the transfer of 1 pair of electrons to reduce FAD to FADH2.
One substrate level phosphorylation reaction results in the formation of GTP from GDP an Pi.

Question 15

How is the TCA cycle controlled?

Answer 15

High ATP, NADH and acetyl-CoA means plenty of energy.
High ADP and NAD+ means lack of energy.
High succinyl-CoA and acetyl-CoA means plenty of precursor molecules for biosynthetic reactions.
There are numerous control points, points where there is inhibition of reaction and steps that require an electron acceptor, either NAD+ or FAD.

Question 16

For each molecules of glucose what is the yield of
ATP
NADH
H+
FADH2
CO2?

Answer 16

ATP - (6-2) = 4
NADH = 10
H+  = 10
FADH2 = 2
CO2 = 6

Question 17

Pyruvate Dehydrogenase complex deficiency is an example of a stage II metabolic disorder. How does it occur and present?

Answer 17

Pyruvate dehydrogenase (PDH) is an enzyme of the pyruvate dehydrogenase complex.
It’s gene is located on the X chromosome. Carrier = X
Presents largely as neurological disease in children.
- Poor muscle tone (hypotonia) and lack or co-ordination
- Retardation and seizures
- Persistent lactic acidosis
- Respiratory problems
It can be seen as brain lesions or defective symmetry of left and right brain hemispheres.

Question 18

What is Fumarate Hydratase Deficiency and “Hereditary Leiomyomatosis and Renal Cell Cancer” (HLRCC)?

Answer 18

Defect in Fumarate Hydratase
Presents as Multiple systemic benign and malignant tumours.
Kidney particular site of malignant metastasis.
Link between TCA cycle and cell proliferation.