13 - Absorptive state Flashcards

1
Q

What is glycolysis?

A

Glycolysis is the sequence of reactions that metabolises one molecule of glucose to two molecules of pyruvate.

Net production of 2 ATP molecules.

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2
Q

What occurs in glycolysis?

A
  • Two phosphorylation reactions forming fructose 1,6-bisphosphate. (2 ATP -> 2 ADP)
  • Cleavage to two molecules of triose phosphate

A series of molecular rearrangements of triose phosphate:

(2x) 2ADP -> (2x) 2ATP

(2x) NAD^+ -> (2x) NADH

Following the molecular rearrangements 2 molecule of pyruvate are formed.

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3
Q

What is the overall reaction of glycolysis?

A

D-glucose + 2 NAD^+ + 2ADP + 2Pi -> 2 pyruvate + 2 ATP + 2 NADH + 2 H^+ + 2 H2O

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4
Q

Why is it necessary for NAD^+ to be regenerated through the metabolism of pyruvate?

A

Without the regeneration of NAD^+ glycolysis will stop.

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5
Q

What are the 2 roles of the glycolytic pathway?

A
  1. Degradation of glucose to generate ATP.
  2. Provision of building blocks for synthetic reactions.
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6
Q

What are the 3 sites of control in glycolysis?

A

Hexokinase:
Inhibited by its product glucose 6-phosphate.

Phosphofructokinase (committed step): Inhibited by - ATP, low pH, citrate.
activated by: AMP, fructose 2,6-bisphosphate

Pyruvate kinase:
Inhibited by - ATP, alanine.
Activated by - 1,6-bisphosphate.

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7
Q

What is the function of phosphofructokinase 2

A

Bifunctional enzyme responsible for the synthesis and hydrolysis of 2,6-bisphosphate.

essentially 2 enzymes stuck together:

phosphofructokinase-phosphofructobisphosphatase.

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8
Q

How is phosphofructokinase 2 regulated?

A

Reciprocal control by phosphorylation of serine 460 by protein kinase A.

Phosphorylated form - phosphatase is active

Dephosphorylated form - kinase is active

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9
Q

What causes the conversion of pyruvate into lactic acid?

A

Lactate is produced by muscles when the body cannot supply enough oxygen.

The body makes more ATP at a cost of creating an oxygen debt.

lactate is oxidised back into pyruvate in the muscle and liver cells using oxygen.

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10
Q

What is mitochondrial oxidative decarboxylation of pyruvate and what happens in the process?

A

Conversion of pyruvate into acetyl CoA - catalysed by pyruvate dehydrogenase complex:

  • Decarboxylation of pyruvate (3C) to a 2C alcohol.
  • Oxidation of alcohol to acetic acid and reduction of NAD^+ to NADH.
  • Esterification of acetic acid to coenzyme A producing acetyl CoA.
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11
Q

What is the function of glycogen and where is it mainly stored?

A

Glycogen functions as a reserve of glucose when metabolic demand for glucose outpaces the cells ability to obtain it from extracellular sources.

Mainly stored in the liver and skeletal muscles.

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12
Q

What are the 2 stages of glycogen anabolism (synthesis), and what enzymes are involved in each stage?

A

Initiation - catalysed by glycogenin.

elongation - catalysed by glycogen synthase and the branching enzyme.

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13
Q

How does glycogenin catalyse the first step of glycogen synthesis?

A

It acts as the primer, to which further glucose monomers can be added.

Glycogenin binds glucose from UDP-glucose to a hydroxyl group of tyrosine 194.

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14
Q

How does glycogen synthase catalyse the second step of glycogen synthesis?

A

Glycogen synthase catalyses glycogen polymerisation.

It can only elongate an existing chain of at least four glucose residues.

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15
Q

How is glycogen synthase regulated?

A

Glycogen synthase is phosphorylated by protein kinase A and glycogen synthase kinase 3.

Phosphorylation converts the active form into the inactive form.

However the inactive form is still active when high levels of the allosteric activator glucose 6-phosphate is present.

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16
Q

What is the equation for the formation of UDP- glucose and what drives this reaction?

A

glucose-1-phosphate + UTP -> UDP glucose + 2 Pi.

Spontaneous hydrolysis of the P-P bond in pyrophosphate PPi drives the overall reaction and makes it irreversible.

17
Q

What happens during glycogen synthesis?

A

Glucose residues are added to the non-reducing terminal residues of glycogen.

UDP is release as a reaction product.

18
Q

What is the branching enzyme in glycogen synthesis called and what does it do?

A

Amylo (1,4 -> 1,6) transglycosylase.

A block of 7 residues from the non-reducing end of the chain is transferred to a more inferior site.

Attaches them by α-(1,6) linkages at least 4 residues from the nearest branch point.

19
Q

Where are fatty acids synthesised and when are they synthesised?

A

Synthesised in the cytoplasm.

Synthesised when more carbohydrate (acetyl CoA) is available than needed for the TCA cycle.

20
Q

What is needed for the formation of a fatty acid chain?

A

1 acetyl CoA + 7 malonyl CoA = palmitate (C16)

21
Q

What is the equation for the formation of malonyl CoA?

A

Acetyl CoA + ATP + HCO3- -> Malonyl CoA + ADP + Pi + H+

22
Q

What occurs to acetyl CoA and malonyl CoA before fatty acid synthesis?

A

Transfer to acyl carrier protein:

Acetyl-CoA + ACP -> Acetyl-ACP + CoA

Malonyl-CoA + ACP -> Malonyl-ACP + CoA

23
Q

How does the fatty acid chain grow?

A

Acetyl-ACP is elongated by the addition of 2C units.

The 2C units are taken from malonyl-ACP (the activated donor).

The transfer is driven by a decarboxylation reaction releasing CO2.

24
Q

What are triglycerides made of, where are they synthesised and how are they transported around the body?

A

3 fatty acid chains + glycerol-3 phosphate = triacylglycerol

Synthesised in liver, intestines and adipose tissue.

Carried around the body by lipoproteins in the plasma.

25
Q

How is glycerol synthesised?

A

Dihydroxyacetone phosphate (DHAP) is reduced by
glycerol 3-phosphate dehydrogenase producing glycerol 3-phosphate:

DHAP + NADH -> G3P + NAD+

26
Q

How are fatty acids activated before TG synthesis and what enzyme catalyses the reaction?

A

Activated by the addition of CoA - takes a lot of energy.

R(OOH) + HS-CoA + ATP -> R(OS-CoA) + AMP + PPi + H2O

Catalysed by Acyl CoA synthetase.

27
Q

What is the first stage in TG synthesis, where does it occur and what catalyses the reaction?

A

Glycerol 3-phosphate + 2R(CO) –> Phosphatidate + 2 CoA

On outer mitochondrial membrane and ER.

Catalysed by glycerol phosphate acyl-transferase.

28
Q

What is the second stage in TG synthesis, where does it occur and what catalyses the reaction?

A

Phosphatidate + H2O -> DAG + Pi + OH-

DAG + R(CO)-CoA -> Triacylglycerol + CoA

First step - phosphatidic acid phosphatase.
Second step - diacylglycerol acyl-transferase.

On endoplasmic reticulum.