Krebs Etc Notes

metabolic reactions

catabolic reactions- breakdown of compounds to release energy and usually involves oxidation

-biologically reduced forms of carbon- fatty acids-palmitic acid

-oxidised to release energy

-invitro- oxidation occurs in one step, complete conversion of the substrate into carbon dioxide and water- energy is released as heat and light

-biological oxidation- oxidation occurs in a step wise process- substrate can be partially or completely oxidised- source of energy is

Anabolic reactions- biosynthesis of complex compounds using small precursors consumes energy-reduction

ATP

-adensine, ribose, triphosphate- releases a lot of energy as it has 2 phosphoanhydride bonds- hydrolysed

-Hydrolysed into ADP and AMP- releases energy – 7.3 kcal/mol, 30.5 Kj/mol

-energy can be coupled for energy requiring reactions- thermodynamically unfavourable reactions can be coupled with the hydrolysis of ATP to form favourable reactions

Compounds with high phosphyrl transfer potential can couple carbon oxidation with ATP synthesis. The energy released from the carbon oxidation is used to form high phosphyrl transfer potential compounds whose cleavage is coupled with ATP synthesis. Glyceraldehyde-3-phosphate is oxidised to 1,3, biphosphage glycerate, electrons released reduce NAD.

Metabolic reactions- controlled

-supply meets demand, forward reactions and reverse reactions don’t occur at the same time- there is no futile cycling

short term

affecting enzyme activity- reversible allosteric control, reversible covalent modification. Hormones control the metabolic activity on a wide range of tissue by controlling the reversible modifications

Long term

control the amount of enzyme present- level of transcription can be controlled

Cycles between organs

-cori cycle- skeletal muscle gives lactate to the liver which converts it to glucose and then returns it to the muscle where it produces ATP

CITRIC ACID CYCLE

-final common pathway for the oxidation of fuel molecules- carbohydrates, fatty acids, amino acids- acetyl coA

-acetyl Coa- 3NADH, 1FADH2, ATP, CoASH

Cycle- small number of intermediates are required to oxidise the acetyl coA- intermediates, reforemed, oxidise more ATP, spin the cycle faster

Cycle- if we block the cycle using malanote at succinate dehydrogenase, for every molecule of ATP hydrolysed, one molecule of oxaloacetate needs to be added.

Entry compound of the TCA cycle is acetyl CoA

-acetyl CoA is synthesised from oxidation of pyruvate, fatty acids, amino acids

-pyruvate is oxidised into acetyl coA by pyruvate dehydrogenase. This enzyme is inactivated by pyruvate dehydrogenase kinase which is activated by ATP, acetyl coA. Inhibition of pyruvate dehydrogenase is relieved through dephosphorylation by phosphoprotein phosphatase.

Oxidation of other intermediates

Oxidation of other substrates can be converted into one of the TCA cycles intermediates where it is oxidised, NADH, ATP- fatty acids, amino acids, enter the cycle as acetyl coA- alpha keto glutarate can be formed by glutamate, histidine, proline, glycine, arginine

-succinyl coA- odd chain fatty acids, propionyl coA -valine, isoleucine, methionine r

Oxaloacetate- asparagines, aspartate,

Biosynthesis of other intermediates

-Krebs cycle- intermediates also as starting molecules for the biosynthesis of other molecules- citrate is used fatty acids- citrate leaves the mitochondria where it is cleaved into the oxaloacetate and acetyl CoA- the Acetyl CoA is then carboxylated to malonyl coA

-alpha ketoglutarate- glutamate and other amino acids

-succinyl coA- porphyrins and haem

-oxaloacetate- asparagines, aspartate (makes urea) glucose

-however if the intermediates were used for biosynthesis it could deplete the concentrations- oxidation of acetyl coa

Anapleurotic reactions are used to prevent this occurring- balance- glutamate is transaminated to form alpha ketoglutarate

And aspartate is transaminated to form oxaloaceate

Anapleurotic reaction 2: Pyruvate carboxylase

-pyruvate and carbondioxide reactions form oxaloacetate- requires the energy of ATP

-pyruvate carboxylase is activated when the concentration of acetyl coA increases, there is insufficient TCA intermediates for its oxidation

-so acetyl coA activates pyruvate carboxylase enzyme increase in oxaloacetate which overcomes this shortage

-anabolic reactions- biosynthesis of complex compounds from small precursors consumes energy involves reduction

Control of the TCA cycle

a)-the control of energy metabolism is not controlled by the substrate availability -but is controlled by the cellular demand of ATP

-Substrate oxidation is increased to match discharge of proton gradient in response to ATP replinishment

-The main regulated enzymes are isocitrate dehydrogenase (inhibited by ATP, and NADH, activated by ADP), Alpha-ketoglutarate dehydrogenase (inhibited by ATP, NADH, succinyl coA).

-TCA cycle is inhibited when cell has no need for further ATP synthesis and activated when it needs to make more ATP.

b) regulated enzymes are activated by a rise in intra mitochondrial Ca levels

-pyruvate dehydrogenase is activated from its inactive form by Ca activated phosphoprotein phosphatase), it activates isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase directly

-the rise in calcium can be caused by adrenaline (flight or fight response) or increased muscle contraction. Both situation increase ATP consumption so the TCA cycle is stimulated to increase ATP synthesis.

-When there is an increased demand for ATP, hormones are released which activates the TCA cycle and increases the oxidation of the substrates. The hormone binds to a cell surface receptor, which leads to a series of intracellular reactions which leads to the release of calcium ions from the ER, specific Ca transport mechanisms in the mitochondria alterls the Ca concentration in the mitochondria to reflect the Ca concentration in the cytoplasm. The increase in Calcium ion concentration activates pyruvate dehydrogenase,...

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