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Metabolism > Metabolism 9 - Integration > Flashcards

Metabolism 9 - Integration Flashcards

1
Q

What is energy intake tightly coordinated with

A

Energy expenditure

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2
Q

Describe the metabolic features of muscles

A

Can have a high ATP requirement during vigorous contraction- relies upon carbohydrate and fatty acid oxidation.

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3
Q

Describe the metabolic features of the brain and nervous tissue

A

continuously high ATP requirement (20% of resting metabolic rate)- cannot utilise fatty acids

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4
Q

Describe the metabolic features of adipose tissue

A

Long term storage site for fatty acids in the form of triglycerides.

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5
Q

Describe the metabolic features of the heart

A

10% of resting metabolic rate- can oxidise fatty acids and carbohydrates

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6
Q

Describe the metabolic features of the liver

A

20% of resting metabolic rate- the body’s main carbohydrate store (glycogen) and a source of blood glucose

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7
Q

What happens to the skeletal muscle during light contraction

A

ATP consumption is met by oxidative phosphorylation (O2, blood-borne glucose and fatty acids are used as fuel).

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8
Q

What happens to the skeletal muscle during vigorous contraction

A

ATP consumption is faster than ATP supply by oxidative phosphorylation (O2 and blood-borne substrate diffusion is limiting). Muscle stores of glycogen are consequently broken down to produce ATP.

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9
Q

What happens to the skeletal muscle in anaerobic conditions

A

Pyruvate is converted into lactate, which can leave the muscle and reach the liver via the blood.

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10
Q

What is a key feature of skeletal muscle

A

It is capable of large and rapid increases in ATP demand during exercise

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11
Q

What substrates can the brain metabolise

A

Ketone bodies and glucose

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12
Q

What can be a consequence of hypoglycaemia

A

Faintness and coma

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13
Q

What can be a consequence of hyperglycaemia

A

Coma and irreversible damage

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14
Q

Why is the heart rich in mitochondria

A

The heart needs to beat constantly and hence is designed for complete aerobic metabolism. The heart utilises TCA substrates ( free fatty acids and ketone bodies).

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15
Q

What are the consequences of a loss of o2 supply to the heart

A

Cell death and myocardial infarction

Energy demand&raquo_space;» supply.

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16
Q

What metabolic processes does the liver participate in

A

Glycolysis, gluconeogenesis and transamination- this reflects in the high metabolic rate of the liver. It also plays a central role in maintaining blood glucose at 4.0-5.5nM. It stores glucose as glycogen, can interconvert nutrient types and plays a key role in lipoprotein metabolism ( transport of triglycerides and cholesterol).

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17
Q

What does glucose need to be converted to before being stored as glycogen

A

Glucose-6-phosphate.

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18
Q

What happens during fasting

A

Rather than enter the TCA cycle, much of the acetyl-coA-produced results in ketone body production.

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19
Q

How can glucose 6 phosphate be used in nucleotide production

A

Via the pentose phosphate pathway in a pathway that generates the bulk of NADPH needed for anabolic pathways ( cholesterol synthesis).

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20
Q

How does the body avoid hypoglycaemia (<3nM)

A

Breakdown liver stores to maintain plasma glucose levels
Release free fatty acids from adipose tissue
convert acetyl coA into ketone bodies via the liver.
Both fatty acids and ketone bodies can be respired by the muscles, making more of the plasma glucose available for the brain.

However, within 12-18hrs all the glycogen stores will be exhausted, hence the need for another pathway to generate glucose- gluconeogenesis.

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21
Q

What is the purpose of gluconeogenesis

A

To produce glucose from non-carbohydrate sources (lactates, amino acids and glycerol).

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22
Q

When is gluconeogenesis important

A

During intense exercise and times of starvation

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23
Q

Where does gluconeogenesis occur

A

The liver (small activity in kidney cortex too)

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24
Q

Is gluconeogenesis a direct reversal of glycolysis

A

No- different enzymes are needed to bypass the irreversible reactions of glycolysis

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25
Q

What does gluconeogenesis require

A

An investment of ATP.

26
Q

Where does lactate enter the gluconeogenesis pathway

A

Lactate is generated by the muscle during strenuous exercise, when the rate of glycolysis exceeds the rate of the TCA cycle and the ETC. Lactate can be taken up by the liver and utilised to regenerate pyruvate by lactate dehydrogenase- cori cycle.

27
Q

Where do amino acids enter the gluconeogenesis pathway

A

Pyruvate or oxaloacetate

28
Q

Where does glycerol enter the gluconeogenesis pathway

A

Hydrolysis of triglycerides yields fatty acids and glycerol. The glycerol backbone is used to generate dihydroxyacetone phosphate- which is converted to G3P.

29
Q

Which enzymes catalyse the irreversible reactions of glycolysis

A

The kinases

30
Q

Describe the process of gluconeogenesis.

A 
Mitochondrial matrix:
Pyruvate --- oxaloacetate (pyruvate carboxylase)
Cytoplasm:
Oxaloacetate --- phosphoenolpyruvate (phosphoenolpyruvate carboxykinase)
Phosphoeneolpyruvate --- G3P
G3P -- F16BP
F16BP --- F6P (F16BP phosphatase)
F6P--- G6P 
G6P -- Glucose (G6P phosphatase)
31
Q

What is the purpose of the addition of 4 high energy bonds

A

To turn an energetically unfavourable process into an energetically favourable one
delta G is -38kJ/mol

32
Q

What are the breakdown products of glucogenic amino acids

A

pyruvate, a-ketoglutarate, succinyl coA, fumerate and oxaloacetate

33
Q

What is meant by a glucogenic amino acids

A

An amino acids who’s carbon skeleton can be used in glucogenesis to produce glucose

34
Q

What are the breakdown products of ketogenic amino acids

A

acetyl coA, acetoacetyl coA.

35
Q

What is meant by ketogenic amino acids

A

The amino acids give rise to skeletons which cannot enter gluconeogenesis but can be used for the synthesis of fatty acids and ketone bodies.

36
Q

Can fatty acids be used in gluconeogenesis

A

no- they are broken down to form acetyl coA, which can be used in the TCA cycle or used to produce ketone bodies.

37
Q

Describe what happens during aerobic respiration

A

When O2 supply is adequate- ATP demands of muscle can be met by oxidative phosphorylation, using glucose and other substrates as fuel.
Glucose is transported from the blood into muscle cells where it can undergo metabolism by glycolysis and the TCA cycle to ultimately generate ATP by the re-oxidation of cofactors.
As the muscle contracts, the demand for ATP increases (actomyosin ATPase, Ca2+ ATPase for cation balance). The increase demand for glucose is met by an increase in the number of glucose transporters in the membrane of muscle cells.
Adrenaline plays a key role in meeting the demand for ATP by increasing the rate of gluconeogenesis by the liver and increasing the release of fatty acids from adipocytes.

38
Q

What are the effects of adrenalin on skeletal muscle contraction during aerobic respiration

A

Increases muscle glycolysis
Increases gluconeogenesis
Increases the release of fatty acids.

39
Q

What are the three ATPases found in muscle cells

A

Actomyosin ATPase
Ca2+ ATPase
Na+K+ ATPase

40
Q

What happens during anaerobic respiration

A

Under anaerobic conditions, the demands of the contracting muscle for ATP cannot be met by oxidative phosphorylation and similarly, the transport of glucose from the blood cannot keep up with the demands of glycolysis. Glycogen in the muscle is therefore broken down to meet these demands. Pyruvate is produced, which is converted into lactate, to replenish NAD+. Lactate is taken up by the liver and is converted back to pyruvate by lactate dehydrogenase. The pyruvate can be used by the liver to generate glucose by gluconeogenesis (recovery).

41
Q

What is the control of metabolic pathways typically centred around

A

Metabolic control is typically centred around reactions that are irreversible, at these points, increases in the rate of enzyme activity greatly increases the rate of the downstream steps. For the greatest steps it is desirable that these steps occur early in the pathway.

42
Q

What are the levels of metabolic control

A

Product inhibition

Under the influence of signalling molecules such as hormones.

43
Q

What concentration is blood glucose concentration usually maintained around

A

4mM

44
Q

What is the key difference between the isoforms of hexokinase found in the liver and muscle cells

A

Both isoforms catalyse the same reaction, but they are maximally active at different concentrations of glucose

45
Q

Describe the characteristics of hexokinase 1 found in muscle cells

A

Km of 0.1- active at low concentrations of glucose and is essentially working at Vmax all the time. It is also highly sensitive to inhibition by G6P. This means that under anaerobic conditions when the rate of the TCA cycle drops, glycolysis slows, Hexokinase 1 is inhibited by accumulating levels of G6P.

46
Q

Describe the characteristics of hexokinase IV found in liver cells.

A

Higher Km of 4mM- less sensitive to blood glucose concentrations. It is also less sensitive to the inhibitory effects of G6P. Liver cells also contain glucose-6-phosphatase which can catalyse the reverse reaction to hexokinase, producing glucose from G6P.

47
Q

When is insulin secreted and what is its function

A

it stimulates uptake and use of glucose and storage as glycogen and fat.

48
Q

When is glucagon secreted and what is its function

A

When blood glucose levels fall, it stimulates the production of glucose by gluconeogenesis and breakdown of glycogen and fat.

49
Q

What are the effects of adrenalin (epinephrine)

A

strong and fast metabolic effects to metabolise glucose for flight or fight.

50
Q

What are the effects of glucocorticoids

A

steroid hormone which increases synthesis of metabolic enzymes concerned with glucose availability.

51
Q

Where is adrenalin and glucocorticoids secreted from

A

The adrenal medulla.

52
Q

What happens when blood glucose levels increase after eating a meal

A

High glucose stimulates insulin release from the pancreas.
Increases glucose uptake by liver- glycogenesis, glycolysis (to produce acetyl coA for FA synthesis).
Increased glucose uptake ang glycogenesis in muscle
Increased triglyceride synthesis in adipocytes
Increased usage of metabolic intermediates throughout the body to a stimulatory effect on anabolic pathways.

53
Q

What happens when blood glucose levels start to fall after eating a meal.

A

Increased glucagon secretion from the islets.
Glucose production in liver from glycogenolysis and gluconeogenesis
utilisation of fatty acid respiration as alternative substrate for ATP production ( important in preserving glucose for the brain).
Adrenaline has similar effects on the liver, but also stimulates skeletal muscle towards glycogen breakdown and glycolysis, and adipose tissue towards fat lipolysis to provide other tissues with alternative substrates to glucose.

54
Q

What happens after prolonged fasting (longer than can be covered by glycogen reserves)

A

Glucagon/Insulin ratio increases further
Adipose tissue begins to hydrolyse triglyceride to provide FAs for metabolism

TCA cycle intermediates are reduced in amount to provide substrates for gluconeogenesis

Protein breakdown provides amino acid substrates for gluconeogenesis
ketone bodies are produced from fatty and amino acids in liver to substitute partially for brain’s requirement for glucose.

55
Q

What is diabetes mellitus

A

A disorder of insulin release and signalling, resulting in an impaired ability to regulate blood glucose concentrations. The overall effects is that metabolism is controlled as if the person is undergoing starvation, regardless of dietary glucose intake.

56
Q

Distinguish between the two types of diabetes mellitus

A

Type 1- individuals fail to secrete enough insulin- beta cell dysfunction
Type 2- individuals respond inappropriately to insulin levels (insulin resistance)

57
Q

What are the complication of diabetes

A

Hyperglycaemia with progressive tissue damage (retina, kidney, peripheral nerves).
Increase in plasma fatty acids and lipoprotein levels with possible cardiovascular complications
Increase in ketone bodies with risk of acidosis.
Hypoglycaemia with consequent coma if insulin dosage is imperfectly controlled

58
Q

Why is glucagon important in protecting against hypoglycaemia

A

Major site of action is liver where glucagon stimulates gluconeogenesis and glycogenolysis.
Insulin deficiency and relative excess of glucagon leads to increased hepatic output of glucose, and thus, hyperglycaemia.

59
Q

How does a cell decide to synthesis glucose or degrade it

A

Phosphofructokinase is allosterically regulated by the binding of a variety of metabolites, which provide both positive and negative feedback regulation. The enzyme is activated by byproducts of ATP hydrolysis, including ADP, AMP and Pi, and is inhibited by ATP. Thus when ATP is depleted and its metabolic byproducts accumulate, phosphofructokinase is turned on and glycolysis proceeds to generate ATP.
The enzymes that catalyses the reverse reaction, Fructose,1,6- bisphosphatase is regulated by the same molecules but in the opposite direction. Thus is activated when phosphofructokinase is turned off.

60
Q

Describe the energetic costs of the reactions in gluconeogenesis

A

Production of a single molecule of glucose consumes 4 molecules of ATP and 2 molecules of GTP. Thus a cell must tightly regulate the balance between glycolysis and gluconeogenesis. If both processes were to proceed simultaneously, they would shuttle metabolites back and forth in a futile cycle that would consume large amounts of energy and generate heat for no purpose.

Metabolism (9 decks)

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