MOLECULES IN METABOLISM

Metabolic Chemistry Related to Overweight

Reactions and molecules in the digestive process

THE FATE OF FOOD

• Food is digested to produce molecules that are used to support life

• In the context of body weight the fate of three classes of food are centralo Carbohydrates (sugars)o Lipids (fats)o Amino acids (from proteins)

• The metabolisms of all three overlap

METABOLIC CHEMISTRY

• Catabolism and Anabolism

• Molecular constituents of food are broken down into smaller molecules (catabolism)o for reassembly into larger molecules (anabolism) such

as fats or proteinso for oxidation to CO2 and H2O and energy

• A balance is required to maintain a stable organism - homeostasis

ENERGY STORAGE

• Energy produced in metabolism is stored in an energy-rich molecule ATP

• Adenosine triphosphate ATP – the battery of life• Biological processes requiring energy use ATP• The accessible energy in ATP lies in the triphosphate

link• Removing one phosphate gives adenosine diphosphate

(ADP) plus energy.

ADENOSINE TRIPHOSPHATE, ATP

adenosine

energy-storage bond

triphosphate

ENERGY STORAGE IN ATP

--- -

-

- -

Adenosine diphosphate (ADP)

Adenosine triphosphate (ATP)

H3PO4

H2O

H3PO4

H2O

energy released

energy stored

The human body produces and consumes its own mass in ATP each day

ENERGY PRODUCTION IN THE CELL

• Energy is produced by oxidation of molecular fuels - small molecules derived from carbohydrates, lipids, proteins

• The oxidation uses oxidised forms of coenzymes ultimately producing CO2, H2O and stored energy

• Energy is stored directly as ATP or as reduced forms of coenzymes that ultimately reduce oxygen to H2O

• Reduction of oxygen to H2O yields more ATP and oxidised form of coenzymes

MOLECULES IN METABOLISM

• Organic molecules from metabolised nutrients often enter metabolic pathway reactions bound to a coenzyme.

• Coenzyme A is an important coenzyme

• Phosphate is often bound to organic molecules

• Oxidation/reduction (electron transport) reactions use NADH NAD+

COENZYME A

                                                       

Usually written as HS-CoA

HS-CoA activates organic molecules for metabolic reactions by binding through HS-group to give reactive “–CoA” species

Acetyl-CoA is an important example

NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD)

nicotinamide

adenine

phosphate

phosphate

Important in oxidation/reduction reactions

1

NAD+ AS AN OXIDISING AGENT

• NAD+ is the main coenzyme for oxidation reactions of metabolic fuels for energy

• NAD+ oxidises other molecules forming NADH and H+

• NADH is oxidised back to NAD+ indirectly by oxygen to give H2O (the electron transport chain)

• For each molecule of NADH reoxidised 2.5 molecules of ATP are produced from ADP

• So energy from oxidising metabolic fuels is stored as ATP

ACETYL CoA – THE CROSSROADS

acetyl-CoA

fatty acids

fatscarbohydratesglycogen

glucose

CO2 + energy

proteins

amino acids

pyruvate

citric acidcycle

glycolysis

fatty acidoxidation

fatty acidsynthesis

Glucose in excess of metabolic needs results in fat deposition

oxidation

SOURCES OF ACETYL CoA

• Three metabolic reactions of food components produce are linkedo Glycolysis of glucoseo Oxidation of fatty acidso Amino acid deamination

• Each can act as a source of Acetyl-CoA• Acetyl-CoA is oxidised in the citric acid (Krebs) cycle

producing energy

THE CITRIC ACID CYCLE

• All air-breathing organisms use the citric acid cycle to generate energy

• Several metabolic pathways deliver acetyl-CoA and other intermediates for the cycle:o Glycolysis of glucose via pyuvate to acetyl-CoAo Fatty acid oxidation via acetyl-CoAo Amino acid deamination via α-ketoacids

CO2

CO2

CH2

C=O

CO2-

CO2-

oxaloacetate

CH3

C=O

SCoAacetyl CoA

CH2

HO-C - CO2-

CH2

CO2-

CO2-

citrate

HO-CH- CO2

-H - CCH2

CO2-

CO2-

isocitrate

C=O

CH2

CO2-

CO2-

CH2

a-ketoglutarate

C=O

CH2

CO2-

CH2

SCoA

succinyl CoA

CO2-

CH2

CO2-

CH2

succinate

CO2-

CH

CO2-

CH

fumarate

CO2-

HOCH

CO2-

CH2

malate

THE CITRIC ACID CYCLE

Two carbon atoms enter as acetyl-CoAand are ejected as to CO2

ENERGY FROM GLUCOSE OXIDATION

• Three processes are involvedo Glycolysis of glucose to two pyruvate moleculeso Pyruvate oxidation to acetyl-CoAo Oxidation of acetyl-CoA to CO2in the citric acid cycle

• Energy stored from oxidation of one molecule of glucose = 36 ATP after all reduced coenzymes are reoxidised

HC=OHC-OH

HO-CHHC-OHHC-OH

CH2OH

HC=OHC-OH

HO-CHHC-OHHC-OH

CH2O-P

CH2OHC=O

HO-CHHC-OHHC-OH

CH2O-P

CH2O-PC=O

HO-CHHC-OHHC-OH

CH2O-P CH2O-PHC-OHHC=O

CH2O-PC=OCH2OH

CH2O-PHC-OH

CH2O-P

CH2O-PHC-OH

CO2-

CH3

C=OCO2

-

CH2OHHC-O-P

CO2-

CH2

C-O-PCO2

-

22 2 2 2

GLYCOLYSIS OF GLUCOSE TO PYRUVATE

glucose glucose 6-phosphate fructose 6-phosphatefructose 1,6-bisphosphate

bisphosphoglycerate3-phosphoglycerate

2-phosphoglyceratephosphoenolpyruvate

pyruvate

Glycolysis of glucose yields 2 pyruvate + 2 ATP + 2 NADH

CONVERSION OF PYRUVATE TO ACETYL CoA

CO2-

CH3

C=O

HSCoA + NAD+ CO2 + NADH

CH3

C=OSCoA

acetyl CoA

ACETYL CoA FROM OXIDATION OF FATTY ACIDS

CH3

(CH2)n

CH2

CH2

C=OSCoA

CH3

CHCHC=OSCoA

(CH2)n

CH3

C=OCH2

C=O

(CH2)n

SCoA

CH3

HC-OHCH2

C=O

(CH2)n

SCoA

CH3

C=O(CH2)n

SCoA

CH3

C=OSCoA

acetyl CoA

n n - 2

pyruvate(mitochondria)

acetyl CoA (mitochondria)

citrate(mitochondria)

citrate (cytosol)

oxaloacetate (cytosoL)

acetyl CoA in cytosol

malate(cytosol)

CO2CO2

glucoseglycolysis pyruvate

(cytosol)in cytosol

oxaloacetate

Fatty acid synthesis from acetyl CoA takes place in the cytosol

ACETYL CoA FROM GLUCOSE FOR FATTY ACID SYNTHESIS

pyruvate(mitochondria)

citrate(cytosol)

malate(cytosol)

CO2

CO2

glucose glycolysis

pyruvate(cytosol)

(cytosol)

CH2

C=O

CO2-

CO2-

oxaloacetate (cytosol)

CH2

HO-C-CO2-

CH2

CO2-

CO2-

CH3

C=O

SCoA

acetyl CoA(mitochondria)

CH3

C=O

CO2-

CO2-

HO-CH2

CO2-

CH2

citrate(mitochondria)

oxaloacetate

ACETYL CoA FROM GLUCOSE FOR FATTY ACID SYNTHESIS

CH3

C=OSCoA

acetyl CoAin cytosol

AMINO ACID METABOLISM

• Amino acids, from protein hydrolysis, can be deaminated to form α-ketoacids

• Some α-ketoacids can be converted to pyruvate or to other intermediates in the citric acid cycle for glucose synthesis

• Others are converted into acetyl-CoA, used in fatty acid synthesis

LIPID (FAT) SYNTHESIS

• Lipids (fats) are fatty acid esters of glycerol• Fatty acids are synthesised by sequential addition of

two-carbon units to acetyl-CoA• Acetyl CoA is derived from several sources, eg

glycolysis of glucose, from dietary carbohydrates• Acetyl CoA is produced in the mitochondria but fatty acid

synthesis takes place in the cytosol • Lipids are synthesised from fatty acids in adipose tissue

and in the liver• Fatty acids for lipid synthesis can also arise from dietary

fats

FATTY ACID SYNTHESIS FROM ACETYL CoA

C=O

SCoA

malonyl CoA

CH2

CO2-

C=O

SACP

malonyl ACP

CH2

CO2-

C=O

SACP

CH2

R

C=O

CH2

R

C=O

SACP

CH2

HC-OH

CH2

R

C=O

SACP

CH2

HC

CH2

R

C=O

SACP

HC

CH2

CH2

R

C=O

SACP

CH2

growing fatty acid chain

CH3

C=OSCoA

acetyl CoA

CHEMICAL CONTROLS

• Hormones are chemicals messengers released by a cell or a gland in one part of the body that transmit messages that affect cells in other parts of the organism.

• Important hormones in human metabolism include: o Ghrelin - the hunger-stimulating hormoneo Leptin - the satiety (full-feeling) hormoneo Glucagon - the stored glucose releasing hormoneo Insulin - stimulates the formation of stored fat from

glucose• Insulin and glucagon are part of a feedback system to

regulate blood glucose levels • Leptin production is suppressed by abdominal fat.