Integrative Metabolism: Significance

Energy Depleted End Products

CO2 H2O NH3

Precursor Molecules

Amino Acids

Sugars Fatty Acids

Nitrogenous Bases

Energy Containing Nutrients

Carbohydrates

Fats Proteins

Cell Macromolecules

Proteins

Polysaccharides Lipids

Nucleic Acids

Catabolism

Anabolism

ATP + Pi NADH+H+

NADPH+H+

FADH2

ADP + Pi NAD+

NADP+

FAD

Acetyl CoA

NADH

NADH

NADH

GLYCOLYSIS

PDH COMPLEX

KREBS CYCLE

ETC

O2

H2O

+ H+

+ H+

+ H+

CO2

CO2

ATP

ATP

ATP

ATP

Waste Products

CO2

NADH2

NH3

e e

e

Pyruvate

Glucose Fatty Acid & Glycerol

Amino Acids

Lipids Proteins

Foods

Carbohydrates

Metabolic Profile of Organs

Pancreas

Liver

Portal Vein

Small Intestine

Brain

Lymphatic System

Adipose Tissue

Skeletal Muscle

Secretes insulin and glucagon in response to changes in blood glucose concentration.

Processes fats, carbohydrates, proteins from diet; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea.

Carries nutrients from intestine to liver.

Absorbs nutrients from the diet, moves them into blood or lymphatic system.

Transports ions to maintain membrane potential; integrates inputs from the body and surroundings; sends signals to other organs.

Carries lipids from intestine to liver

Synthesizes, stores, and mobilizes triacylglycerols.

Uses ATP to do mechanical work.

Acetyl-CoA

TCA Cycle ETS ATP

Fatty Acids

Glycolysis

Role of the Liver: Carbohydrate Metabolism

Glucose

Glucose

Glucose-6-P

Fructose-6-P

Pyruvate

Glycogen

Cell

Blood

Pentose Phosphate

Cycle

NADP+ NADPH

DNA, RNA

Ribose

Role of the Liver: Lipid Metabolism

Acetyl-CoA

Fatty acyl-CoA

Malonyl-CoA

Triacylglycerol

Fatty Acids

Glycerol

Acetoacetate

β-hydroxybutyrate

Lipoprotein Complexes

Ketone Bodies

FA β-oxidation

ATP

FA Synthesis

Cholesterol

Phospholipids

Acetone + CO2

Role of the Liver: Amino Acid Metabolism

Glucose

Gluconeogenesis

Acetyl-CoA

CO2

Glucose-6-P

Glycogen Metabolism

Amino acids as precursors to synthesize plasma proteins

Ketone Bodies

Acetoacetate

β-hydroxybutyrate

Leu Phe Tyr Trp Lys

Ala Cys Gly Ser Thr

Pro His Arg

Ile Met Val Thr

Methylmalonyl CoA

Propionyl-CoA

Gln

Glu

Phe Tyr

Tricarboxylic Acid Cycle Urea

Cycle

NH3 CO2

Carbamoyl-P

Ornithine

Citrulline

Arginine

Argininosuccinate

Urea

Aspartate

Asn

Succinate Succinyl CoA

Fumarate

Malate

Oxaloacetate Citrate

Isocitrate CO2

CO2

α-Ketoglutarate

Pyruvate

Role of Skeletal Muscles

Glycogen

Glucose-1P

Glucose-6P

Pyruvate

ENERGY (ATP)

DURING EXERCISE DURING STARVATION

Muscle Proteins Fatty Acids & Ketone Bodies

(Provided by Liver)

Used as Fuels

Lactate Alanine

Transamination Lactate Dehydrogenase

Mobilization of Glycogen Stores

Catabolism

Role of Adipose Tissue

Hormone-sensitive lipase – key to mobilization of TG stores from adipose cells.

Glucose (from the Liver)

VLDL (from the Liver)

Glucose Fatty Acids

Glycerol 3-phosphate

Fatty Acyl CoA

Fatty Acids Glycerol

Glycerol (to the Liver)

Fatty Acid-albumin Complexes (to the Liver)

Triacylglycerols

Hormone-sensitive Lipase

• The activity of heart muscle is constant and rhythmic

• The heart functions as a completely aerobic organ and is very rich in mitochondria prefers fatty acid as fuel

• Continually nourished with oxygen and free fatty acid, glucose, or ketone bodies as fuel

Role of Heart Muscle

ATP

Heart Cells: Rich In Mitochondria Fatty Acids: Preferred Fuel Source

Heart: Aerobic Metabolism

Lactate

CO2

NADH

Acetyl-CoA

Glycogen

ATP

ADP + Pi

CYTOSOL

ADP + Pi

Contractile Work, S.R. Ca2+ uptake, Ion homeostatis

Fatty Acids

TG ATP

ATPase

ADP + Pi

H+ O2

MITOCHONDRION

CPT-I Fat

Glucose

G 6-P

Pyruvate

Acetyl-CoA

Citric Acid Cycle

GLUT

Glycolysis

PDH

Fatty Acid β-Oxidation

MCT

Electron Transport

Chain

Role of the Brain

• Very high respiratory metabolism – depends on glucose supply from the blood

• Under fasting condition, brain can use ketone bodies – β-hydroxybutyrate as fuel

Starvation Ketone Bodies

Glucose Normal Diet

ADP + Pi

CO2

Electrogenic Transport By Na+K+ Atpase

Active transport – requires ATP expenditure

ATP

Take Home Points Metabolism serves different purposes for different tissues •  Liver: master regulator of blood glucose homeostasis •  Key organ performing gluconeogenesis, fatty acid synthesis, and ketone bodies

synthesis to be used by other organs for fuel •  Brain: uses glucose almost exclusively, except during starvation when it uses

ketone bodies as fuels •  Skeletal muscles: use glycogen as source of energy – under starvation, muscle

proteins are used as fuels – ketone bodies synthesized in liver also used a fuels. •  Under vigorous exercise, muscle produces lactate from pyruvate – recycled to

the liver to produce additional glucose •  Under starvation, alanine from skeletal muscle shuttled to liver for additional

glucose production by liver •  Adipose tissue: serves primarily as triglyceride stores