C7 - Integration & Reg. of Metabolism Flashcards

1
Q

What substrates are critical in connecting the metabolism of CHO, lipids + proteins?

A

Pyruvate + Acetyl-CoA

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2
Q

What does the energy status of the cell largely determine?

A

The direction in which mol. flow

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3
Q

What happens if ATP is needed in the cell?

A

Pyruvate from glycolysis is sent to mitochondria.

Decarboxylated to Acetyl-CoA + oxidised via TCA cycle to prod ATP through oxidative phosphorylation.

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4
Q

What can FA’s be catabolised to in the mitochondria?

A

Acetyl-CoA then produce ATP via TCA cycle + oxidative phosphorylation.

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5
Q

What happens when CHO + lipids are in short supply?

A

aa are converted to pyruvate + Acetyl-CoA

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6
Q

What else declines when the energy status of the cell declines?

Why?

A

Conc of:

  • Acetyl-CoA
  • Citrate
  • ATP

Due to ⬇️ glycolysis, lipolysis + TCA cycle reactions.

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7
Q

What does ⬆️ ADP + AMP in cells indicate?

A

That ATP has been used up in anabolic reactions therefore more ATP is needed.

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8
Q

What are the metabolic responses to low cellular energy status?

A

⬆️ glycolysis

⬆️ TCA cycle

⬇️ Gluconeogenesis

⬆️ FA b-oxidation

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9
Q

What are the metabolic responses to abundant cellular energy status?

A

⬇️ Glycolysis

⬇️ TCA cycle

⬆️ Gluconeogenesis

⬆️ FA synthesis

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10
Q

Low energy cellular status

What is the cellular signal causing ⬆️ FA b-oxidation?

A

⬇️ Malonyl-CoA

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11
Q

Low energy cellular status

What is the cellular signal causing ⬇️ gluconeogenesis?

A

⬆️ AMP

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12
Q

Low energy cellular status

What is the cellular signal causing ⬆️ TCA cycle?

A

⬆️ ADP

⬆️ pyruvate

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13
Q

Low energy cellular status

What is the cellular signal causing ⬆️ glycolysis?

A

⬆️ AMP

⬇️ ATP

⬇️ Citrate

⬇️ Acetyl-CoA

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14
Q

Abundant energy cellular status

What is the cellular signal causing ⬇️ glycolysis?

A

⬆️ ATP

⬆️ Citrate

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15
Q

Abundant energy cellular status

What is the cellular signal causing ⬇️ TCA cycle?

A

⬆️ ATP

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16
Q

Abundant energy cellular status

What is the cellular signal causing ⬆️ gluconeogenesis?

A

⬆️ Acetyl-CoA

⬆️ Citrate

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17
Q

Abundant energy cellular status

What is the cellular signal causing ⬆️ FA synthesis?

A

⬆️ Citrate

⬆️ Malonyl-CoA

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18
Q

What acts as an indicator of the FED state?

A

Release of insulin by b-cells of the pancreas in response to ⬆️ blood glucose levels.

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19
Q

Which is the 1st tissue to be able to use dietary glucose?

A

Liver

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20
Q

What can happen to the glucose retained in the liver?

A

May enter glycolysis or glycogenesis.

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21
Q

What can happen to excess glucose in the liver?

A

Can be converted to FAs

(Only rly happens when energy intake exceeds energy expenditure).

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22
Q

What can chronic overconsumption of CHO lead to in the liver?

A

TAG accumulation + ⬆️ secretion of TAG-rich VLDL into circulation.

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23
Q

When does the postabsorptive state evolve into the fasting state?

A

After 18-48hrs of NO food intake.

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24
Q

What happens in the fasting state?

A

aa from muscle protein breakdown provides substrates for gluconeogenesis.

Release of FAs from adipose tissue continue to occur during the early fasting state. = Supplying many tissues w. FAs for ATP prod while the glycerol is converted to glucose in liver.

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25
FASTING STATE What is the shift to gluconeogensis using aa mediated by?
⬆️ secretion of glucagon + cortisol.
26
What happens to proteins in muscle cells in the fasting state?
Hydrolysed at an accelerated rate to provide aa for gluconeogenesis.
27
What does the accelerated rate of proteins being hydrolysed in the fasting state result in?
Large daily losses of nitrogen through urine.
28
Of all aa, which are the only ones that can't directly contribute to gluconeogensis and why?
Leucine + lysine Due to being ketogenic.
29
Which cycle is important in the fasting state?
Alanine-Glucose cycle
30
What happens in the starvation state?
New + more dramatic metabolic fuel shift occurs to spare body protein: 1. Accelerated lipolysis 2. ⬆️ use of FAs as fuel in certain tissues 3. ⬆️ use of glycerol for gluconeogenesis 4. ⬆️ ketone body synthesis + utilisation
31
What happens in regards to free FAs in the starvation state?
Free FAs are released by adipose tissue to become primary fuel for kidneys, liver, heart + skeletal muscle.
32
Where is insulin secreted from?
b-cells of the pancreas
33
Why is insulin secreted?
In response to ⬆️ blood glucose
34
In which state is insulin critical and why?
Fed state to prevent hyperglycaemia
35
How does insulin promote the uptake of glucose into muscle + adipose tissue?
By stimulating the translocation of GLUT4 from storage vesicles to the cell surface. Also ⬆️ glycogen synthesis in liver + skeletal muscle.
36
What does insulin inhibit?
Gluconeogenesis in the liver Lipolysis in adipose tissue Proteolysis in muscle
37
Where and why is glucagon secreted?
Secreted by a-cells of pancreas When blood glucose levels decline.
38
What are the main tissues w/ glucagon receptors?
Liver + adipose tissue
39
What does glucagon do in the liver?
⬆️ gluconeogenesis + glycogenolysis, then FA oxidation + ketone body prod as starvation progresses Inhibits glycogen synthesis
40
What does glucagon do in adipose tissue?
⬆️ lipolysis
41
Where is epinephrine produced?
Adrenal medulla from the aa's phenylalanine + tyrosine.
42
What does epinephrine function as in the NS and in the circulation?
NT in the NS Stress hormone in circulation.
43
What does the binding of epinephrine to alpha receptors in the pancreas do?
Inhibits insulin secretion
44
What does the binding of epinephrine to beta receptors in the pancreas do?
Stimulate glucagon secretion
45
Where is cortisol produced?
Adrenal cortex from cholesterol in response to low blood glucose.
46
How does cortisol travel in the circulation?
Bound to albumin + corticosteroid-binding globulin.
47
What happens to cortisol once delivered to target cells?
Passes freely through plasma membranes Binds to intracellular cortisol receptors in the cytosol.
48
What does Cortisol do in the liver?
Stimulates gluconeogensis + glycogenolysis ⬆️ activity of G-6-P = promoting release of free glucose into circulation.
49
What does Cortisol do in skeletal muscle?
Stimulates glycogenolysis Inhibits translocation of GLUT4 to cell membrane
50
What does Cortisol do in adipose tissue?
Stimulates lipolysis = providing free FAs for energy use in liver, kidneys, cardiac + skeletal muscle.
51
Where is the Growth Hormone (GH) produced?
By the anterior pituitary gland
52
How is the GH transported?>
In the circulation bound to GH-binding protein
53
Why is GH secreted?
In response to fasting + strenuous exercise.
54
What does GH do in adipose tissue?
Stimulates lipolysis
55
What does GH do in skeletal muscle?
Stimulates lipoprotein lipase = promoting TAG uptake from circulating VLDL.
56
What does GH do in liver?
⬆️ TAG uptake from VLDL by inducing the expression of lipoprotein lipase + hepatic lipase.
57
By what 4 mechanisms is regulation achieved by?
-ive or +ive modulation of allosteric enzymes by effector compounds Hormonal activation by covalent modification or induction of specific enzymes Directional shifts in reversible reactions by changes in reactant or prod conc. Translocation of enzymes w/in cell.
58
What are allosteric enzymes?
Enzymes that change their conformational shape upon binding of an effector.
59
What can allosteric mechanisms do to a pathway?
Can stimulate or suppress the enzymatic activity of a pathway.
60
Examples of allosteric modulators
AMP ADP ATP
61
REGULATION OF METABOLISM What happens if ATP is abundant + ADP is scarce?
Energy-releasing pathways are -ively modulated therefore reduce the prod of additional ATP.
62
What does covalent modulation involve?
Binding or unbinding of a group by a covalent bond
63
What can specific hormones do to a gene?
Influence (induce or suppress) the expression of a gene
64
What are the main brain regions responsible for the regulation of energy homeostasis?
Hypothalamus Brainstem
65
What is believed to have important roles in the ST regulation of appetite?
Neural + endocrine signalling from the gut
66
Where is ghrelin released from?
Stomach
67
What does ghrelin do to appetite?
⬆️ it
68
What does peripheral administration of ghrelin do?
Reduces fat use
69
What does chronic central ghrelin infusion do?
⬆️ the expression of enzymes that promote fat storage in adipose tissue.
70
Where is the hormone PYY found?
L cells throughout the gut
71
When is PYY released into circulation?
After a meal
72
What is PYY release reduced by?
Fasting
73
What does acute peripheral administration of PYY do?
⬇️ food intake
74
What does central or peripheral administration of GLP-1 stimulate?
Insulin release
75
What does peripheral administration of GLP-1 inhibit?
Appetite
76
CCK stimulates the release of what other gut hormone
PYY
77
What does the binding of epinephrine to beta receptors in adipose tissue + skeletal muscle do?
Stimulates lipolysis Inhibits FA synthesis.
78
What does the binding of epinephrine to alpha receptors in the liver + skeletal muscle do?
Stimulates glycogen breakdown + inhibits glycogen synthesis Skeletal muscle only - Stimulates glycolysis