Integration and Regulation of Metabolism
So far there has only been studying of metabolism as separate pathways, but in
reality they interact.
Pathways within cells interact, cells within tissues interact and organs within the
body as a whole interact
Different organs and tissues have different needs, they may use the same molecule
but in different ways (e.g. on using it to store, other for energy source, or to generate
a new molecule – biosynthesis)
These needs and the way they use these particular metabolites may change with
changing circumstances such as disease state
These changes may affect how one organ interacts with another
Each organ has a unique metabolic profile ->
Brain
The brain requires a lot of glucose, usually around 100-120g daily. Over half of the
energy consumed is used for Na+/K+ transport to maintain the membrane potentials
of neurones and also for synthesis of neurotransmitters.
The brain lacks energy stores however, so in order for it to use glucose it has glucose
transporters appropriate for its needs. This is GLUT3, which has a low Km, meaning
it’s maximally active at concentrations of glucose that would be seen at any time, so
even when below normal – it is saturated under most conditions. This is good
because it won’t be affected by fluctuations in glucose, so brain won’t be starved of
its main energy source.
Danger point is when plasma glucose drops below 2.2mM.
Normally fatty acids are used not for energy but for membrane synthesis (but will
use them if in dire need, as well as ketone bodies).
Cardiac Muscle
Cardiac muscle is dependent on aerobic respiration (if you deprive = angina).
It has little/no glycogen stores, instead its main source of energy is fatty acids,
supplied by the liver. Followed by ketone bodies and lactate.
The reason why fatty acids is because it yields a much greater amount of ATP
Adipose Tissue
Adipose tissue is the main reserve for triglycerides, being stored. Most of these fats
have been made by the liver and then transported to the adipocytes, although
adipocytes can synthesise fat themselves.
Overall, the majority of FA we get from our diet, that have been delivered by
chylomicrons or as intermediate through the liver.
, Kidney
The major role of the kidney is to produce urine, with the plasma being filtered up to
60x daily, with only a small volume of urine being produced. This is through water-
soluble material largely being reabsorbed to prevent loss.
The kidney although only 0.5% of body mass consumes 10% of the body’s energy –
mainly for active transport
During starvation the kidney may contribute half of the blood glucose through
gluconeogenesis.
Liver
The liver plays a central role in regulating metabolism, for
-Carbohydrates
-Fatty acids
-Amino acids
Most compounds absorbed by the gut pass through the liver, the liver also provides
fuel for other tissues such as brain, muscle and other peripheral organs.
The liver itself takes its energy from α-ketoacids ( α-ketogluterate, pyruvate,
oxaloacetate)
The liver has a different enzyme make up compared to other tissues, quite
importantly it has glucokinase enzyme as well as hexokinase for phosphorylating
glucose.
Glucokinase has a high Km, so only maximally active when glucose conc. is elevated,
it is there to help keep blood glucose constant.
Control of Blood Glucose by Liver Metabolism
Glucose is transported into hepatocytes by GLUT-2, which activity is not regulated by
insulin. Glucose is immediately phosphorylated to G6P by glucokinase.
Glucose-6-phosphatase is present in the liver also allowing conversion of G6P ->
glucose in gluconeogenesis/glycogenolysis which can be transported out by GLUT-2.
Muscle Glucose Metabolism
So far there has only been studying of metabolism as separate pathways, but in
reality they interact.
Pathways within cells interact, cells within tissues interact and organs within the
body as a whole interact
Different organs and tissues have different needs, they may use the same molecule
but in different ways (e.g. on using it to store, other for energy source, or to generate
a new molecule – biosynthesis)
These needs and the way they use these particular metabolites may change with
changing circumstances such as disease state
These changes may affect how one organ interacts with another
Each organ has a unique metabolic profile ->
Brain
The brain requires a lot of glucose, usually around 100-120g daily. Over half of the
energy consumed is used for Na+/K+ transport to maintain the membrane potentials
of neurones and also for synthesis of neurotransmitters.
The brain lacks energy stores however, so in order for it to use glucose it has glucose
transporters appropriate for its needs. This is GLUT3, which has a low Km, meaning
it’s maximally active at concentrations of glucose that would be seen at any time, so
even when below normal – it is saturated under most conditions. This is good
because it won’t be affected by fluctuations in glucose, so brain won’t be starved of
its main energy source.
Danger point is when plasma glucose drops below 2.2mM.
Normally fatty acids are used not for energy but for membrane synthesis (but will
use them if in dire need, as well as ketone bodies).
Cardiac Muscle
Cardiac muscle is dependent on aerobic respiration (if you deprive = angina).
It has little/no glycogen stores, instead its main source of energy is fatty acids,
supplied by the liver. Followed by ketone bodies and lactate.
The reason why fatty acids is because it yields a much greater amount of ATP
Adipose Tissue
Adipose tissue is the main reserve for triglycerides, being stored. Most of these fats
have been made by the liver and then transported to the adipocytes, although
adipocytes can synthesise fat themselves.
Overall, the majority of FA we get from our diet, that have been delivered by
chylomicrons or as intermediate through the liver.
, Kidney
The major role of the kidney is to produce urine, with the plasma being filtered up to
60x daily, with only a small volume of urine being produced. This is through water-
soluble material largely being reabsorbed to prevent loss.
The kidney although only 0.5% of body mass consumes 10% of the body’s energy –
mainly for active transport
During starvation the kidney may contribute half of the blood glucose through
gluconeogenesis.
Liver
The liver plays a central role in regulating metabolism, for
-Carbohydrates
-Fatty acids
-Amino acids
Most compounds absorbed by the gut pass through the liver, the liver also provides
fuel for other tissues such as brain, muscle and other peripheral organs.
The liver itself takes its energy from α-ketoacids ( α-ketogluterate, pyruvate,
oxaloacetate)
The liver has a different enzyme make up compared to other tissues, quite
importantly it has glucokinase enzyme as well as hexokinase for phosphorylating
glucose.
Glucokinase has a high Km, so only maximally active when glucose conc. is elevated,
it is there to help keep blood glucose constant.
Control of Blood Glucose by Liver Metabolism
Glucose is transported into hepatocytes by GLUT-2, which activity is not regulated by
insulin. Glucose is immediately phosphorylated to G6P by glucokinase.
Glucose-6-phosphatase is present in the liver also allowing conversion of G6P ->
glucose in gluconeogenesis/glycogenolysis which can be transported out by GLUT-2.
Muscle Glucose Metabolism
