Metabolic Pathways and Insulin Regulation

Catabolic pathways

Pathways that break down molecules to release energy, examples include glycolysis, glycogenolysis, beta-oxidation, and lipolysis.

Anabolic pathways

Pathways that build molecules, examples include glycogenesis, gluconeogenesis, lipogenesis, and fatty acid synthesis.

Preferred fuel source of the heart

Ketone bodies.

Fuel source for erythrocytes

Only glycolysis; produces lactate.

Role of kidneys in metabolism

Use ~8g/day of lactate for ATP production.

Preferred fuel for intestines and immune cells

Glutamine.

Fuel source for spermatozoa

Fructose.

Unique metabolic feature of cancer cells

Aerobic lactate production (Warburg effect).

Examples of altered metabolic states

Fed (anabolic), Fasting (catabolic), Starvation, Exercise, Thermogenesis, Alcoholism, High fructose intake, Insulin resistance/Diabetes.

Key metabolic substrates

Glucose, Amino acids, Fatty acids.

Primary anabolic hormone

Insulin.

Insulin's effect on glycogen metabolism

↑ Glycogen synthase (↑Glycogenesis), ↓ Phosphorylase (↓Glycogenolysis).

Insulin's effect on gluconeogenesis

↓ F-1,6-bisphosphatase → ↓Gluconeogenesis.

Insulin's effect on glycolysis enzymes

↑ PFK2 → ↑ F-2,6-P2 → ↑ PFK1 and ↑ Glycolysis; ↑ Pyruvate kinase → ↑ Glycolysis.

Insulin's effect on fat synthesis

↑ Acetyl CoA carboxylase → ↑ FA synthesis.

Insulin's effect on fat breakdown

↓↓ Hormone-sensitive lipase → ↓ Lipolysis.

Insulin's effect on Acetyl CoA production

↑ Pyruvate dehydrogenase → ↑ Acetyl CoA.

Insulin's effect on glycolysis in liver

↑ Glucokinase → ↑ Glc → G-6-P → ↑ Glycolysis.

Insulin's effect on NADPH production

↑ Malic enzyme → ↑ NADPH for FA synthesis.

Insulin's effect on GNG enzymes

↓ PEP carboxykinase → ↓ GNG.

Insulin's effect on lipogenesis enzymes

↑ Glycerol-3-P acyltransferase and ↑ Lipoprotein lipase.

GLUT1 and GLUT3 Km and location

Low Km; found in most tissues.

GLUT2 Km and location

High Km; found in liver and pancreatic beta cells.

GLUT4 Km and regulation

Medium Km; insulin-induced in muscle and adipose tissue.

Hexokinase I-III properties

Low Km; found in most tissues.

Hexokinase IV (Glucokinase) properties

High Km; not inhibited by G-6-P; found in liver and pancreas.

Isozymes in metabolism

Allow tissue-specific regulation of substrate use.

HFCS and its metabolic consequence

High-fructose corn syrup; less insulin release but faster liver metabolism → more lipogenesis.

Fructose bypassing glycolysis control

Bypasses PFK1 and hexokinase; F-1-P stimulates pyruvate kinase.

Consequence of excess fructose metabolism

↑ Pyruvate → ↑ Acetyl CoA → ↑ FA and TG synthesis.

Effect of artificial sweeteners on insulin

Sweet taste triggers insulin release → Hypoglycemia and sugar craving.

Ethanol metabolism regulation

Ethanol is oxidized first; ↑ NADH and ↓ NAD+ affects other pathways.

Effect of alcohol on fat metabolism

↑ NADH inhibits β-oxidation; ↑ Acetyl CoA → ↑ TG synthesis.

Effect of alcohol on gluconeogenesis

↓ Pyruvate → ↓ GNG → Hypoglycemia.

Summary of insulin's role

Insulin promotes anabolic pathways: glycolysis, glycogenesis, lipogenesis.

Effect of fructose and ethanol on metabolism

Bypass regulatory steps → uncontrolled liver lipogenesis.