Integrated Metabolism

What is metabolism?

Integrated network of biochemical reactions.

What are catabolic pathways?

Degradative pathways breaking proteins, carbohydrates, lipids into CO₂, NH₃, H₂O.

What are anabolic pathways?

Synthetic pathways forming complex end products from simple precursors.

What is an amphibolic pathway?

Pathway functioning as both catabolic and anabolic.

Example of amphibolic pathway?

TCA cycle.

Role of TCA cycle in catabolism?

Oxidises acetyl‑CoA to CO₂ and H₂O.

Role of TCA cycle in anabolism?

Provides intermediates for biosynthetic pathways.

What are the four mechanisms regulating metabolism?

Availability of substrates, allosteric regulation, covalent modification, induction/repression of enzyme synthesis.

Example of allosteric regulation in glycolysis?

Fructose‑2,6‑bisphosphate activates phosphofructokinase.

Example of covalent modification?

Glycogen phosphorylase inactive when dephosphorylated.

Effect of insulin on enzyme synthesis?

↑ insulin → ↑ synthesis of anabolic enzymes.

What defines the well‑fed (absorptive) state?

2–4 hours after a meal with ↑ glucose, amino acids, triglycerides, ↑ insulin, ↓ glucagon.

Primary fuel for all tissues in well‑fed state?

Glucose.

Main metabolic response in well‑fed state?

↑ synthesis of triglycerides, glycogen, proteins.

Liver carbohydrate metabolism in well‑fed state?

↑ glucose uptake, ↑ glycogen synthesis, ↑ glycolysis/TCA, ↑ HMP pathway, ↓ gluconeogenesis.

Liver lipid metabolism in well‑fed state?

↑ fatty acid synthesis, ↑ triglyceride synthesis.

Liver protein metabolism in well‑fed state?

↑ amino acid degradation, ↑ protein synthesis.

Adipose carbohydrate metabolism in well‑fed state?

↑ glucose uptake, ↑ glycolysis → glycerol‑P, ↑ HMP pathway.

Adipose lipid metabolism in well‑fed state?

↑ triglyceride synthesis, ↓ triglyceride degradation.

Muscle carbohydrate metabolism in well‑fed state?

↑ glucose uptake, ↑ glycogen synthesis.

Muscle lipid metabolism in well‑fed state?

FA from chylomicrons/VLDL (secondary fuel).

Muscle protein metabolism in well‑fed state?

↑ protein synthesis, ↑ uptake of branched‑chain amino acids.

Brain metabolism in well‑fed state?

Uses glucose exclusively (~140 g/day), no glycogen stores.

What triggers early fasting state?

↓ blood glucose → ↓ insulin, ↑ glucagon.

Liver metabolism in early fasting?

Glycogenolysis, gluconeogenesis, ketone body production begins.

Adipose metabolism in early fasting?

Lipolysis → FA + glycerol.

Muscle metabolism in early fasting?

Uses fatty acids as fuel.

Brain metabolism in early fasting?

Still dependent on glucose.

What fuels the brain in prolonged starvation?

Ketone bodies (acetoacetate, β‑hydroxybutyrate, acetone).

After weeks of starvation, major brain fuel?

Ketone bodies.

What happens after TAG depletion in starvation?

Protein degradation accelerates → organ failure and death.

What are the two priorities in starvation metabolism?

Maintain plasma glucose for brain and mobilise FA + ketone bodies for other tissues.

Which fuel store is largest in the body?

Triglycerides.

How much body protein can be used for energy without fatal compromise?

Only about one third.

Metabolic inter‑relationship in well‑fed state?

Digestive system provides nutrients, liver distributes, adipose stores TG, muscle uses glucose/FA, brain uses glucose.

Metabolic inter‑relationship in starvation?

Liver gluconeogenesis + ketogenesis, adipose lipolysis, muscle proteolysis, brain shifts to ketone bodies.

What is the absorptive state duration?

2–4 hours after ingestion of a normal meal.

What hormones dominate in well‑fed state?

↑ insulin, ↓ glucagon.

What hormones dominate in fasting state?

↓ insulin, ↑ glucagon.

What stimulates glycogen synthesis in liver?

Inactivation of glycogen phosphorylase and activation of glycogen synthase.

What stimulates HMP pathway in liver?

↑ glucose‑6‑phosphate and NADPH utilisation in lipogenesis.

What stimulates glycolysis in liver?

↑ insulin:glucagon ratio → activates phosphofructokinase and pyruvate kinase.

What inhibits gluconeogenesis in liver?

Insulin:glucagon ratio → inactivation of fructose‑1,6‑bisphosphatase.

What provides glycerol‑3‑phosphate for TG synthesis in liver?

Glycolytic metabolism of glucose.

What provides fatty acyl‑CoA for TG synthesis in liver?

De novo synthesis from acetyl‑CoA and hydrolysis of TG from chylomicron remnants.

What stimulates glucose uptake in adipose tissue?

↑ insulin.

What supplies glycerol‑P for TG synthesis in adipose tissue?

Glycolysis.

What inhibits TG degradation in adipose tissue?

Inactive hormone‑sensitive lipase due to insulin.

What percentage of oxygen consumption is by resting muscle?

~30%.

What percentage of oxygen consumption is by exercising muscle?

Up to 90%.

Which amino acids are taken up by muscle in well‑fed state?

Branched‑chain amino acids (leucine, isoleucine, valine).

What percentage of body weight is adipose tissue in a 70 kg man?

~14 kg.

What percentage of body weight can adipose tissue reach in obesity?

Up to 70%.

What occupies nearly the entire volume of adipocytes?

Triglyceride droplet.

What percentage of basal oxygen consumption is by brain?

~20%.

What percentage of adult weight is brain?

~2%.

What is the daily glucose requirement of brain?

~140 g/day.

Does brain store glycogen?

No, completely dependent on blood glucose.

What happens during transition from fed to fasting?

Glycogen depletion, lipolysis, gluconeogenesis, ketone body production.

What stimulates glucagon secretion?

↓ blood glucose.

What are glucagon’s effects?

Mobilises glycogen, inhibits glycogen/FA synthesis, stimulates gluconeogenesis.

What are plasma levels of glucose, amino acids, TG in fasting?

Decreased.

What is insulin:glucagon ratio in fasting?

Low.

What metabolic processes occur in fasting?

Degradation of TG, glycogen, protein.

What fuels are mobilised in starvation?

Fatty acids from adipose, ketone bodies from liver.

What substrates are used for gluconeogenesis in liver?

Amino acids from muscle, glycerol from adipose.

What fuels are used by muscle in fasting?

Fatty acids.

What fuels are used by brain in prolonged starvation?

Ketone bodies.

What happens after several weeks of starvation?

Ketone bodies major fuel for brain.

What causes death in prolonged starvation?

Loss of heart, liver, kidney function due to protein degradation.