Liver and gluconeogenesis Flashcards

1
Q

Why is glucose used?

A

The requirement for glucose is continuous
* Glc is the preferred fuel source for all tissues
* some tissues have a continuous dependence on glucose

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2
Q

What is the blood glucose concentration in the human body?

A
  • physiological circulating glc concentration 3.9-6.2 mM
  • average fasting 4.4-5 mM for most adults
  • if it drops to 2.5 or less coma and death can result
  • if it rises for an extended time, dehydration, wasting of body tissue and eventually death will result
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3
Q

What is the roles of glucose?

A
  • It is a source of energy
    glucose → pyruvate gives 2 ATP
    glucose → CO2 + H2O gives 31 ATP
  • it is a source of NADP
  • needed for synthetic reactions (fatty acids, steroids) and drug metabolism
  • it is a source of pentose sugars for for synthetic reactions (nucleotides, DNA )
  • it is a source of carbon for other sugars and glycoconjugates (mannose,galactose, glucuronic acid
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4
Q

What are advantages of glucose as a metabolic fuel?

A
  • Water soluble , so does NOT require a carrier in the circulation
  • can cross the blood-brain barrier
  • can be oxidised anaerobically
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5
Q

What are disadvantages of glucose as a metabolic fuel?

A
  • relatively low yield of ATP/mole compared to fatty acids
  • osmotically active
  • In high concentrations can directly damage cells or lead to accumulation of toxic by-products (fructose, sorbitol)
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6
Q

What are Pathways involving glucose

A
  • all tissues use glucose
  • the liver can provide glc for other tissues
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7
Q

What is the role of glucose in skeletal muscle?

A

glycolysis - Anaerobic muscle contraction
Glycolysis/TCA cycle - energy
Glycogen synthesis and degradation - Energy store for
muscle contraction

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8
Q

What is the role of glucose in heart/brain muscle?

A

Heart/brain
Main Pathway - Glycolysis/TCA
Function - ENERGY

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9
Q

What is the role of glucose in Adipose tissue?

A

Adipose tissue
Main pathway - glycolysis
Function - Production of glycerol P’ for TAGS

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10
Q

What is the role of glucose in Erythrocyte?

A

Tissue - Erythrocyte
Main pathway - glycolysis
Pentose phosphate pathway
(shunt)
Energy - NADPH

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11
Q

What is a role of glucose in the liver?
Function of the pathways?

A
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12
Q

What are the sources of blood glc?

A
  1. Diet
  2. Liver Glycogen
  3. Liver gluconeogenesis
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13
Q

What is Gluconeogenesis?

A

In conditions of carbohydrate deprivation glc is synthesised from non-carbohydrate sources in the liver
* Lactate
* glycerol
* other monosaccharides
* glucogenic amino acids (all except leu, lys)
* NOT FROM FATTY ACIDS

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14
Q

What is the irreversible reaction of gluconeogenesis?

A

gluconeogenesis is not simply the reversal of glycolysis
There are 3 irreversible reactions in glycolysis that must be bypassed.
They are catalysed by:
* hexokinase/ glucokinase
* phosphofructokinase
* pyruvate kinase

  • all in the cytosol
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15
Q

Role of Pruvate Kinase?

A

pyruvate kinase catalyses the conversion of PEP to pyruvate
pyruvate carboxylase and PEP carboxykinase are needed for the conversion of pyruvate to PEP in gluconeogenesis

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16
Q

Regulation of gluconeogenesis

A
  • Mobilisation of substrate
    – glycerol from fat breakdown
    – amino acids from muscle protein breakdown
  • activation of enzymes
    – G6Pase F1,6bisPase,PEPCK
    (insulin/glucagon is low)
    – activation pyruvate carboxylase by acetyl CoA
17
Q

What is blood glucose maintenance?

A
  • Insulin, glucagon and adrenaline (and to a lesser extent cortisol) and glucose itself, signal and co- ordinate the activities of
    – liver
    – adipose tissue – muscle tissue
  • Maintain physiological blood glc concentrations needed to preserve brain function (and other tissues dependent on glc)
18
Q

Describe?

A

Islets of Langerhans in the pancreas

  • beta cells secrete insulin
  • alpha cells secrete glucagon
19
Q

What is the different between insulin and glucagon?

A
  • insulin is an anabolic hormone. It promotes synthesis and storage
  • glucagon is a catabolic hormone. It promotes degradation of stored fuel
20
Q

Sites of insulin action on metabolism

A
21
Q

What is metabolic effects of insulin: Liver?

A
  • Inhibition of gluconeogenesis
  • activation of glycogen synthesis (glycogen synthase activated)
  • Increased Fatty Acid synthesis and lipid assembly
  • Increased aa uptake and protein synthesis
22
Q

What is the process of the liver in the fed state?

A
23
Q

Metabolic effects of insulin: Muscle

A
  • Increased glucose uptake by increasing glucose transporters (GLUT4)
  • Increased aa uptake and protein synthesis
  • activation of glycogen synthesis (glycogen synthase activated)
24
Q

What is the process of the muscle: FED STATE?

A
25
Q

What is process of MUSCLE: AEROBIC?

A
26
Q

What is the Metabolic effects of glucagon?

A
  • increase in blood glucose
    – ↑ glycogenolysis and gluconeogenesis (liver).
  • Increase in circulating fatty acids and ketone bodies
    – ↑ adipose tissue lipolysis, ↑fatty acid oxidation in the liver and ketone body formation.
  • Decrease in plasma amino acids
    – ↑uptake by the liver for gluconeogenesis.
27
Q

What is the LIVER: FASTING STATE?

A
28
Q

BRAIN: FED OR FASTING

A
29
Q

ERYTHROCYTE : FED OR FASTING

A