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Y1 - PoM - Week 1 > Integration of Metabolism > Flashcards

Integration of Metabolism Flashcards

1
Q

What can muscles (including cardiac) metabolise?

A

Carbohydrate and fatty acid oxidation

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2
Q

What can the brain and nervous tissue metabolise?

A

Only glucose (and ketones), NOT fatty acids

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3
Q

What does adipose tissue store?

A

Fatty acids as triglycerides

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4
Q

What does the liver store?

A

Carbohydrates - glucose as glycogen

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5
Q

What are the metabolic features of skeletal muscle?

A

During light contraction, ATP demand is met by oxidative phosphorylation
During vigorous contraction: muscle stores glycogen, which can be broken down to fuel ATP production, and under anaerobic conditions, pyruvate is converted to lactate, which can be sent to the liver via the bloodstream

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6
Q

What are the metabolic features of the brain?

A

Requires a continuous supply of glucose
Cannot metabolise fatty acids
Ketone bodies (e.g. β-hydroxy-butyrate) can partially substitute for glucose
Too little glucose (hypoglycaemia) causes faintness and coma
Too much glucose (hyperglycaemia) can cause irreversible damage

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7
Q

What are the metabolic features of the heart (cardiac muscle)?

A

Beats constantly
Rich in mitochondria - designed for aerobic metabolism
Utilises TCA cycle substrates, e.g. free fatty acids, ketone bodies
Loss of O2 supply to the heart leads to cell death and myocardial infarction

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8
Q

What are the metabolic features of the liver?

A

Is the immediate recipient of nutrients absorbed by the intestines
Undertakes many metabolic processes e.g. glycolysis, gluconeogenesis, transamination, lipoprotein metabolism, maintain blood glucose levels etc
Stores glucose as glycogen

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9
Q

What can excess glucose-6-phosphate be used to generate?

A

Glycogen

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10
Q

In which 2 tissues is glycogen stored?

A

In the liver and muscle

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11
Q

What triggers glycogenesis?

A

Insulin

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12
Q

What can excess Acetyl-CoA be used to generate?

A

Fatty acids, stored as triglycerides in adipose tissue

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13
Q

What happens during fasting to the acetyl CoA?

A

Used in in ketone body production

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14
Q

What can be a source of amino acids?

A

Pyruvate and other TCA cycle intermediates

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15
Q

What can be a source of nucleotide production?

A

Backbones of certain molecules and Glucose-6-phosphate via the pentose phosphate pathway

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16
Q

What else does the Glucose-6-phosphate via the pentose phosphate pathway generate?

A

NADPH needed for anabolic reactions, e.g. cholestrol synthesis

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17
Q

During fasting, how does the body avoid a hypoglycaemic coma? (plasma glucose conc. of less than 3mM)

A

Maintains glucose levels by:

  1. Break down glycogen stores in the liver
  2. Release fatty acids from adipose tissue
  3. Convert Acetyl CoA into ketone bodies via the liver
  4. Gluconeogenesis
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18
Q

How long does it typically take until all glycogen stores are exhausted?

A

12-18 hrs

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19
Q

What occurs after gycogenolysis?

A

Gluconeogenesis

20
Q

What is gluconeogenesis?

A

The generation of glucose from pyruvate

21
Q

What is the gluconeogenesis pathway?

A

Pyruvate (3C) —> oxaloacetate (4C) —> phosphoenol pyruvate (3C)
Which is converted to G3P (3C) and joined to a molecule of DHAP (3C) to form fructose-1,6-biphosphate (6C)
fructose-1,6-biphosphate (6C) —> fructose-6-phosphate (6C) —> glucose-6-phosphate (6C) —> glucose (6C)

22
Q

What other metabolic products can join into the gluconeogenesis pathway?

A

Lactate - product of anaerobic respiration taken up by the liver, regenerates pyruvate using lactate dehydrogenase
Amino acids - diet or breakdown of skeletal muscle
Glycerol - used to regenerate DHAP
(but NOT fatty acids)

23
Q

What can fatty acids be used for? (as they cannot enter the gluconeogenesis cycle directly)

A

Production of ketone bodies that can be used by muscle and brain

24
Q

Why are there bypass reactions in gluconeogenesis?

A

There are 3 irreversible reactions catalysed by kinases in glycolysis, so the gluneogenesis pathway cannot directly follow the exact reversal of glycolysis. Instead, the bypass uses pyruvate to form oxaloacetate

25
Q

What is required for the bypass reactions?

A

4 additional enzymes
4 ATP molecules (To make the reaction energetically feasible - just the reversal of glycolysis would be +90 kJ/mol, but the bypass reactions make if -38kJ/mol)

26
Q

What occurs during moderate exercise (with adequate oxygen supply)?

A

Muscles are supplied with glucose from the blood via glucose transporters, ATP demands are met by oxidative phosphorylation

27
Q

What occurs as exercise continues and as the muscle contracts, ATP demand increases?

A
  1. An increase in the number of glucose transporters on the membranes of muscle cells
  2. Release of adrenaline
28
Q

What key roles is adrenaline responsible for during heavy exercise?

A
  1. Increasing the rate of glycolysis in muscle
  2. Increasing the rate of gluconeogensis by the liver
  3. Increasing the release of fatty acids from adipocytes
29
Q

What occurs in muscles when ATP demand cannot be matched by oxygen supply?

A

Anaerobic respiration - ATP demand cannot be met by oxidative phosphorylation
Substrate level phosphorylation (i.e glycolysis) increases

30
Q

What occurs in muscles when ATP demand cannot be matched by the transport of glucose?

A 
Glycogen within the muscle is broken down to generate glucose for glycolysis
Lactate increases (due to anaerobic respiration)
Lactate is taken up by the liver and converted to glucose (gluconeogenesis) to further supply glycolysis
31
Q

How can metabolic pathways be controlled?

A
  1. End product inhibition

2. Hormones

32
Q

What is end product inhibition?

A

When increasing levels of the product formed reduces the rate of reaction

33
Q

How does glycolysis undergo product inhibition and how is it different in muscles than the liver?

A

In the first irreversible step of glycolysis, hexokinase is required
2 different forms of Hk: Hk I in muscle Hk IV in liver
Both are maximally active at different concentrations of glucose
Hk I: active at low concentrations, highly sensitive to inhibition by the product glucose-6-phosptate (G6P)
Hk IV: less sensitive to blood glucose concentrations, less sensitive to the inhibitory effects of (G6P)

34
Q

What is used to convert glucose-6-phosptate (G6P) to glucose and where does it occur?

A

Glucose 6-phophatase

Found only in the liver, not muscle

35
Q

What can be used to compare the relative activities of enzymes and what are the parameters?

A

KM - Michaelis constant

The concentration of substrate at which an enzyme functions at a half-maximal rate (Vmax)

36
Q

Compare the KM of Hk I and Hk IV?

A 
Hk I (muscle): high glucose affinity, KM = 0.1 mM, highly sensitive to G6P inhibition
Hk IV (liver): low glucose affinity, KM = 4 mM, less sensitive to G6P inhibition
37
Q

Hormones that increase blood sugar levels?

A

Glucagon (production of glucose by gluconeogenesis and glycogenolysis and also causes lipolysis)
Adrenaline
Glucocorticoid (cortisol), increases synthesis of metabolic enzymes concerned with glucose availability

38
Q

Hormones that decrease blood sugar levels?

A

Insulin (increases hepatic glucose uptake making glycogen, and performing glycolysis to make fatty acids)

39
Q

What happens after a meal when blood glucose levels rise?

A

Increased glucose uptake – used for glycogen synthesis (in liver and muscle)
Glycolysis - acetyl-CoA produced is used for fatty acid synthesis (in liver).
Increased triglyceride synthesis in adipose tissue.
Increased usage of metabolic intermediates throughout the body due to a general stimulatory effect on synthesis and growth

40
Q

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

A

Increased glucagon secretion (and reduced insulin) from islets.
Glucose production in liver resulting from glycogen breakdown and gluconeogenesis.
Utilisation of fatty acid breakdown as alternative substrate for ATP production (important for preserving glucose for brain).

41
Q

How is adrenaline similar/different to glucagon?

A

Similar effects on liver
However, also stimulates skeletal muscle towards glycogen breakdown and glycolysis, and adipose tissue towards fat lipolysis

42
Q

What happens after prolonged fasting when blood glucose levels can no longer be covered by glycogen reserves?

A

Glucagon/insulin ratio increases further
Adipose tissue begins to hydrolyse triglycerides to provide fatty acids 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 acids and amino acids in liver to substitute partially the brain’s requirement for glucose

43
Q

What is Diabetes mellitus?

A

A disorder of insulin release and signalling, resulting in an impaired ability to regulate blood glucose concentrations

44
Q

What is the different between Type 1 and Type 2 diabetes?

A

Type I diabetes= failure to secrete enough insulin (β-cell dysfunction), whereas, Type II diabetes = failure to respond appropriately to insulin levels (insulin resistance)

45
Q

What are some complications associated with diabetes?

A

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

46
Q

What is the breakdown of amino acids used for?

A

20 amino acids can form 7 products that can enter the TCA cycle

Y1 - PoM - Week 1 (21 decks)

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