Carbohydrate Metabolism

normal glucose concentration in peripheral blood

5.6 nM

GLUT 2

captures the excess glucose for storage

low-affinity transporter in hepatocytes and pancreatic cells

GLUT 4

adipose tissue and muscle

stimulated by insulin

Glycolysis

glucose —> 2 pyruvate molecules

Hexokinase

low K_m

inhibited by glucose 6-phosphate (its product)

Glucokinase

present in hepatocytes and pancreatic beta islet cells

High K_m

induced by insulin

Phosphofructokinases (PFK)

PFK 1: rate limiting enzyme

induced by AMP (low energy) and inhibited by ATP (high energy)

PFK 2: produces F2,6-BP that activates PFK-1

activated by insulin and inhibited by glucagon

Glyceraldehyde-3-phosphate dehydrogenase

produces NADH

anerobic glycolysis

NADH produced is oxidized by lactate dehydrogenase

pyruvate dehydrogenase complex

Pyruvate -*→ Acetyl CoA

• CoA + pyruvate dehydrogenase + NAD⁺

Inhibited by acetyl CoA

Glycogenesis

synthesis of glycogen granules

• glycogen synthase: creates 1,4 glycosidic links between glucose molecules

• Branching Enzyme: moves block of oligoglucose from one chain and adds it to growing glycogen

Glycogenolysis

breakdown of glycogen

• Glycogen Phosphorylase: removes glucose 1-phosphate molecules by breaking glycosidic bonds

• Debranching enzyme: moves a block of Oligoglucose from one branch and connects it to the chain

Gluconeogenesis

Synthesis of glucose molecules

promoted by glucagon and epinephrine

inhibited by insulin

Gluconeogenesis important substrates

• Glycerol 3-phosphate

• Lactate

  • Glucogenic amino acids

Important enzymes of gluconeogenesis

• Pyruvate carboxylase

• Phosphoenolpyruvate Carboxykinase

• Fructose-1,6-Biphosphatase

  • Glucose-6-Phosphatase

NAD⁺

high-energy electron acceptor

potent oxidizing agent

NADPH

electron donor, reducing agent

Products of the Pentose Phosphate pathway

NADPH and ribose 5-phosphate

Pyruvate dehydrogenase complex

pyruvate enters the mitochondria via active transport and is oxidized and decarboxylated

Products: 2-carbon acetyl group and carbon dioxide

Pyruvate Dehydrogenase Complex equation

Pyruvate + CoA-SH + NAD⁺ —> acetyl-CoA + CO₂ + H⁺

Step 1 of the Citric Acid Cycle

Citrate Formation:

• Acetyl-CoA undergoes condensation to form citryl-CoA

  • Citryl-CoA is then Hydrolyzed to yield Citrate and CoA-SH

Step 2 of citric acid cycle

Citrate isomerized to isocitrate:

• Citrate —> cis-Aconitate —> Isocitrate

Step 3 of Citric acid cycle

Ketoglutarate and CO₂ formation:

• Isocitrate oxidized to oxalosuccinate

• Oxalosuccinate is then decarboxylated to produce Ketoglutarate and CO₂

• NAD⁺ is reduced to NADH

Step 4 of citric acid cycle

Succinyl-CoA and CO₂ formation:

• Oxalosuccinate is oxidized and decarboxylated to form Succinyl-CoA and CO₂

• NAD⁺ reduced to NADH

Step 5 of citric acid cycle

Succinate formation:

• Hydrolysis of Succinyl-CoA results in Succinate

• GDP is phosphorylated to GTP

  • ATP is generated

Step 6 of citric acid cycle

Fumarate formation:

• inner mitochondrial membrane

• Succinate undergoes oxidation to form fumarate

• FAD is reduced to FADH₂

Step 7 of citric acid cycle

Malate formation:

• hydrolysis of fumarate produces malate

Step 8 of citric acid cycle

Oxaloacetate formed anew:

• Oxidation of malate to oxaloacetate

  • Final NAD⁺ is reduced to NADH

Total ATP generated from pyruvate and glucose

Pyruvate: 12.5 ATP per

Glucose: 25 ATP per

Electron chemical gradient

An influx of [H⁺] causes a decrease in pH and an increase in voltage

Key regulators of oxidative phosphorylation

O₂ and ADP

F₀ portion

ion channel, allows protons to flow down the gradient

F₁ Portion

uses energy released by gradient to phosphorylate ADP into ATP

Products of glycolysis

2 NADH and 2 ATP