Metabolic Homeostasis Flashcards

1
Q

What are the two requirements the Metabolism must meet

A
  • Synthesise that not provided by diet
  • Protect our internal environment from toxins & changing external conditions
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2
Q

What are the four basic types of metabolic pathway

A
  • Fuel oxidative pathways
  • Fuel storage & mobilisation
  • Biosynthesis pathways
  • Detoxification/waste disposal pathways
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3
Q

What is considered to be the ‘Anabolic’ pathway

A

Synthesis of large molecules
(e.g. biosynthesis & fuel storage pathways)

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4
Q

What is consider to be the ‘Catabolic’ pathways

A

Breakdown of large molecules
(e.g. fuel oxidation pathways)

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5
Q

The control of the balance between substrate availability and need, manifested by anabolic vs catabolic pathways, is known as

A

Metabolic Homeostasis

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6
Q

Main body tissues (e.g. brain, RBC, kidney medulla, skeletal muscle) require glucose
Therefore what is the normal concentration of glucose in the blood

A

80-100 mg/dL

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7
Q

A significant decrease in glucose concentration (<60 mg/dL) will result in

A

limited brain metabolism
Hypoglycemia
(Glucose influx lowers due to low Km of brain-blood barriers)

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8
Q

If there is a significant increase in blood glucose….

A
  • There are hyperosmolar effectos = neurological deficits & possible coma
  • Non-enzymatic glycoslation of proteins
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9
Q

The balance between use, release, storage by different tissues is achieved in 3 ways
What are they?

A
  • Blood (nutrients)
  • Hormones
  • Central Nervous system
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10
Q

What is the major anabolic hormone

A

Insulin

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11
Q

Around 80 mg/dL is considered the release threshold for insulin
Where is it released from

A

Released from β-cells of islets of Langerhans (pancreas)

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12
Q

What tissues/organs will degrade insulin

A
  • Liver
  • Kidney
  • Skeletal muscle
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13
Q

How does glucose stimulate insulin to be released
What is the process behind this

A
  • At a high conc of glucose, the GLUT-2 transporter will transport glucose into β-cells
  • Here it will become phosphorylated glucokinase forming glucose-6-phosphate (trapping glycose in the cell)
  • Causes metabolism within the cell to increase, producing ATP, which will inhibit K⁺ channel
  • This causes membrane polarisation and Ca²⁺ will move into cell
  • Vesicles containing insulin, will fuse with outer membrane, releasing insulin into blood
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14
Q

What is the name of the most important ‘contra-insular’ hormone of metbolism control

A

Glucagon

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15
Q

Where is glucagon released from

A

α-cells of pancreas

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16
Q

Where does Glucagon act upon

A

Liver and adipose tissue

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17
Q

Secretion of Glucagon is regulated by

A

Glucose & Insulin
Levels of glucagon build as both fall

18
Q

The secretion of Glucagon promotes

A

Glucose production (fuel mobilisation)
* via glycogenolysis
* via gluconeogenesis

19
Q

Both insulin and glucagon bind to receptors on a cell’s surface
This causes

A

Initiate intracellular signaling cascades
Can lead to covalent modification/allosteric regulation of enzymes
Affect enzyme gene transcription

20
Q

Insulin will ……….. cell receptor

A

Autophosphorylates

21
Q

Glucagon binding causes …..

A

2nd messenger formation

22
Q

There are two temportal controls seen for these enzymes, what are they?

A
  • Minutes-hours: changes in enzyme catalytic activity/kinetics
  • Hours-Days: regulation of enzyme synthesis
23
Q

The absorptive state is known as ….
What will it involve

A

The ‘well-fed’ state (in the 2-4hrs period after a normal meal)
Involve elevated insulin-to-glucagon ratio, with lots of readily available substrates - hence an ‘anabolic state’

24
Q

Once insulin is stimulated in the well-fed state, what will then occur

A
  • Increased glucose uptake by Hepatocytes (with insulin dependent gluocse transporters)
  • Increased phosphorylation of glucose - using glucokinase forming glucose-6-phosphate
  • Converted into glycogen by glycogen synthase (allosterically regulated)
  • Increased activity of Pentose Phosphate pathway forming NADPH
  • Leads to high amounts of glycolysis
25
Q

What happens to Fatty Acid synthesis during the absorptive state

A

Fatty acid synthesis at the liver increases during the absorptive state due to acetyl CoA & NADPH availability
As well as Acetyl CoA Carboxylase being activated

26
Q

What happens to Triacylglyercol synthesis during the absorptive state

A

Increased Triacylglycerol synthesis
Due to increased acyl CoA presence & also due to hydrolysis of TAG component from chylomicrons

27
Q

If amino acids are not used for protein synthesis in the liver which is increased in the absorptive state, what happens to them

A

They are exported to other tissue for use or degradation (deamination)
Carbon skeleton degraded to pyruvate and TCA intermediates

28
Q

If no food is taken in after the end of the Absorptive state (~4hrs post food) we enter the …….

A

Fasting state

29
Q

What happens to glucose, amino acid and TAG levels during the fasting state

A

Levels fall

30
Q

What happens to hormone levels during the fasting state

A

Insulin decreases
Glucagon and Adrenaline increase

31
Q

The fasting state is therefore an….

A

‘Catabolic state’

32
Q

The main role of the fasting state is to maintain plasma glucose levels
How is this done?

A
  • Inter-tissue exchange of compoents
  • Mobilisation of fatty acids from adipose tissue & ketone bodies from liver to supply energy to other tissue
33
Q

The flow of intermediates through the metabolic pathways is controlled by

A
  • Substrate availibility
  • Allosteric regulation of enzymes
  • Covalent modification of enzymes
  • Induction-repression of enzyme synthesis
34
Q

During the fasting state, most enzymes used in the Absorptive state are now

A

Phosphorylated and inactive

35
Q

What 3 enzymes are highly active within the fasting state

A
  • Glycogen phosphorylase
  • Glycogen phosphorylase kinase
  • Hormone-sensitive lipase
36
Q

What two processes occur within the fasting state

A
  • Glycogenolysis (releasing glucose) + gluconeogenesis
  • Lipolysis (releasing FA’s & glycerol)
37
Q

The carbon skeletons from gluconeogenesis are derived from

A

Glucogenic amino acids
lactate from muscle
Glycerol from adipose tissue

38
Q

Fatty acid oxidation is the major energy source in liver tissue
Where does this occur

A

Adipose tissue
Fat metabolism can also influence gluconeogeneis through activiting different hormones
Ketone body synthesis occurs outside the liver

39
Q

What is the hypercatabolic state

A

Extreme states of catabolic activity occur with injury (e.g. burns & septic stress)
Mobilise body protein, fat & carbohydrates from bodily stores and negative nitrogen balance (skeletal muscle degradation)
Patients may become hyperglycemic

40
Q

What is the main mediator of the hypercatabolic state

A

Cortisol
* Encourages ubiquitin-mediated proteolysis and induced glutamine synthase

41
Q

During the hypercatabolic state amino acids are used in a …..

A

Prioritised fashion