Introduction to glucose metabolism

Overview of glucose metabolism

Objectives

• Recognizing the critical importance of glucose as the main carbohydrate of blood & main fuel of human cells.

• Recognizing glucose transport into cells

• Recalling the sources of blood glucose in feed & fasting states.

• Understand the basic concepts & directions (pathways) of metabolism.

General importance of carbohydrates in human body

1- Provide energy through metabolism pathways and cycles 2- Store energy in the form of: starch (in plants) glycogen (in animals and humans)

3- Supply carbon for synthesis of other compounds.

4- Form structural components in cells and tissues.

A constant source of GLUCOSE is an absolute requirement for human life as it is:

1- Preferred energy of the brain

2- Required energy source for cells with no or few mitochondria (as RBCs)

3- Essential source of energy for exercising muscles (substrate for anerobic glycolysis)

Critical importance of glucose

Glucose transport into cells

1- Na+-independent facilitated diffusion transport:

 • Transport occurs with concentration gradient• No require for energy (i.e. ATP)• It is conducted by a group of at least 14 glucose transporters (GLUT-1 to 14)

 

GLUT-1 is abundant in RBCs & Brain GLUT-2 is found in liver, kidney & b-cells of the pancreas Function in both directions (from blood to cells & from cells to blood) GLUT-3 primary glucose transporter in neurons GLUT-4 is abundant in adipose tissue & skeletal muscles Number is increased by insulin GLUT-5 is the primary transporter of fructose GLUT-7 is expressed in gluconeogenic tissue (as the liver) mediates glucose flux across ER membrane

Glucose transport into cells (cont.)

Glucose transporters (GLUT)

2- Na+-monosaccharide cotransporter system

• Glucose is transported against a concentration gradient from low glucose concentrations outside the cell to higher concentrations within the cell

• Energy-requiring process

• It is a carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na+, which is transported into the cell at the same time

• This type of transport occurs in the epithelial cells of the intestine & renal tubules

Glucose transport into cells (cont.)

GLUCOSE TRANSPORT & INSULIN

Sources of Glucose to human Body

Glucose can be obtained from three primary sources:

Carbohydrate in Diet:

• Carbohydrates are sources for glucose of the body after meals.• Excess glucose is stored in the form of glycogen in liver & skeletal muscles.

Glycogen degradation (Glycogenlysis):

• Glycogen (synthesized from glucose molecules) is stored in liver & skeletal muscles.• In cases of fasting, liver glycogen is degraded to yield glucose for blood.• In cases of muscular exercise, muscle glycogen is degraded to secure glucose for muscles as a source

of energy. Gluconeogenesis (Glucose Synthesis):

• It is the synthesis of glucose from non carbohydrate sources (as some amino acids)• It occurs in prolonged fasting

Sources of glucose of carbohydrate diet

1- Free Monosaccharides:

mainly glucose & fructose Fructose is converted into glucose in liver

2- Disaccharides:

- Sucrose (glucose & fructose) - Lactose (glucose & galactose) - Maltose (glucose & glucose) They are digested into monosaccharides (glucose, fructose & galactose) in the intestine. Fructose & galactose are converted into glucose in the liver

3-Polysaccharides:

- Starch (plant source e.g. rice, potato, flour) - Glycogen (animal source) They are digested into glucose in the GIT

Metabolic pathways of glucose

GLUCOSEGlycogenesis

Gluconeogenesis

Hexosesfructose

& galactose

Glycogenolysis

Glycolysis

Krebs cycle

HMP/PPP

Hexosesfructose & galactose

PRODUCTION Utilization

Pathways of glucose utilization

1- Catabolic pathways:

1- For providing energy (ATP): Glycolysis

Anaerobic Glycolysis: end product is lactate Aerobic Glycolysis: end product is pyruvate

2- For providing synthetic products: Hexose monophosphate pathway (Produces NADPH & Ribose 5-Phosphate)

2- Synthetic pathways: Glycogen synthesis

GLUCOSE

Pyruvate

Acetyl CoA

Citric Acid Cycle

NADH & FADH2

Electron transport chain (flow of electrons)

Formation of ATP (oxidative phosphorylation)

Utilization of

Glucose

HEXOSE MONOPHOSPHATE PATHWAY

Ribose-5 Phosphate Glycogen

GLYCOGEN SYNTHESIS

GLYCOLYSISNADPH

LactateOxygen

&Mitochondria

No OxygenNo MitochondriaOR BOTH