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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 central

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Metabolic chemistry related to overweight

Metabolic Chemistry Related to Overweight

Reactions and molecules in the

digestive process


The fate of food
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 central

    • Carbohydrates (sugars)

    • Lipids (fats)

    • Amino acids (from proteins)

    • The metabolisms of all three overlap


Metabolic chemistry
METABOLIC CHEMISTRY

  • Catabolism and Anabolism

  • Molecular constituents of food are broken down into smaller molecules (catabolism)

    • for reassembly into larger molecules (anabolism) such as fats or proteins

    • for oxidation to CO2 and H2O and energy

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


Energy storage
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 TRIPHOSPHATE, ATP

energy-storage bond

triphosphate

adenosine


Energy storage in atp
ENERGY STORAGE IN ATP

Adenosine triphosphate (ATP)

-

H2O

-

-

-

energy released

H3PO4

-

energy stored

H2O

-

-

H3PO4

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

Adenosine diphosphate (ADP)


Energy production in the cell
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 metabolism1
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
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 DINUCLEOTIDE (NAD)

1

phosphate

nicotinamide

phosphate

adenine

Important in oxidation/reduction reactions


Nad as an oxidising agent
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 – THE CROSSROADS

carbohydrates

glycogen

glucose

fats

glycolysis

proteins

pyruvate

fatty acids

oxidation

amino acids

fatty acid

oxidation

acetyl-CoA

fatty acid

synthesis

citric acid

cycle

CO2 + energy

Glucose in excess of metabolic needs results in fat deposition


Sources of acetyl coa
SOURCES OF ACETYL CoA

  • Three metabolic reactions of food components produce are linked

    • Glycolysis of glucose

    • Oxidation of fatty acids

    • 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
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:

    • Glycolysis of glucose via pyuvate to acetyl-CoA

    • Fatty acid oxidation via acetyl-CoA

    • Amino acid deamination via α-ketoacids


THE CITRIC ACID CYCLE

CH3

C=O

CO2-

acetyl CoA

SCoA

C=O

CH2

CO2-

CO2-

CO2-

CO2

CH2

CH2

H - C

HO-C - CO2-

- CO2-

HO-CH

CH2

CO2-

CO2-

CO2-

oxaloacetate

citrate

isocitrate

CH2

Two carbon atoms enter as acetyl-CoA

and are ejected as to CO2

CH2

CO2-

C=O

HOCH

CO2-

CO2-

CO2-

a-ketoglutarate

CH2

CH2

CO2-

CH

CO2-

CH2

CH2

malate

CH

C=O

CH2

CO2-

SCoA

CO2-

CO2

fumarate

succinylCoA

succinate


Energy from glucose oxidation
ENERGY FROM GLUCOSE OXIDATION

  • Three processes are involved

    • Glycolysis of glucose to two pyruvate molecules

    • Pyruvate oxidation to acetyl-CoA

    • 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


GLYCOLYSIS OF GLUCOSE TO PYRUVATE

HC=O

HC=O

CH2O-P

CH2OH

CH2OH

CH3

CH2O-P

CH2O-P

CH2

HC-OH

HC-OH

C=O

C=O

HC-OH

HC-O-P

C=O

C=O

C-O-P

HO-CH

HO-CH

HO-CH

HO-CH

CH2O-P

CH2OH

CO2-

HC-OH

HC-OH

HC-OH

HC-OH

HC-OH

HC-OH

HC-OH

HC-OH

CH2O-P

CH2O-P

CH2OH

CH2O-P

CH2O-P

HC-OH

HC=O

glucose

glucose 6-phosphate

fructose 6-phosphate

fructose 1,6-bisphosphate

CO2-

CO2-

CH2O-P

2

2

2

2

HC-OH

2

CO2-

pyruvate

2-phosphoglycerate

bisphosphoglycerate

phosphoenolpyruvate

3-phosphoglycerate

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


Conversion of pyruvate to acetyl coa
CONVERSION OF PYRUVATE TO ACETYL CoA

CH3

HSCoA + NAD+

CO2 + NADH

C=O

CO2-

CH3

acetyl CoA

C=O

SCoA


Acetyl coa from oxidation of fatty acids
ACETYL CoA FROM OXIDATION OF FATTY ACIDS

n n - 2

CH3

CH3

CH3

CH3

(CH2)n

(CH2)n

(CH2)n

(CH2)n

CH3

CH

HC-OH

C=O

CH2

(CH2)n

CH

CH2

CH2

CH2

C=O

C=O

C=O

C=O

C=O

SCoA

SCoA

SCoA

SCoA

SCoA

CH3

acetyl CoA

C=O

SCoA


Acetyl coa from glucose for fatty acid synthesis
ACETYL CoA FROM GLUCOSE FOR FATTY ACID SYNTHESIS

glycolysis

pyruvate

(cytosol)

pyruvate

(mitochondria)

acetyl CoA

(mitochondria)

glucose

in cytosol

oxaloacetate

CO2

citrate

(mitochondria)

acetyl CoA

in cytosol

malate

(cytosol)

oxaloacetate

(cytosoL)

citrate

(cytosol)

CO2

Fatty acid synthesis from acetyl CoA takes place in the cytosol


Acetyl coa from glucose for fatty acid synthesis1
ACETYL CoA FROM GLUCOSE FOR FATTY ACID SYNTHESIS

CH3

CH3

C=O

C=O

SCoA

CO2-

acetyl CoA

C=O

CH2

glycolysis

pyruvate

(mitochondria)

glucose

CO2-

(cytosol)

CO2-

pyruvate

(cytosol)

(mitochondria)

oxaloacetate

oxaloacetate

(cytosol)

CO2-

CO2

CH2

CO2-

HO-C-CO2-

HO-CH2

CH3

CH2

acetyl CoA

in cytosol

CH2

C=O

CO2-

CO2

CO2-

SCoA

citrate

(cytosol)

citrate

(mitochondria)

malate

(cytosol)


Amino acid metabolism
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
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, egglycolysis 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
FATTY ACID SYNTHESIS FROM ACETYL CoA

growing fatty acid chain

C=O

SACP

C=O

CO2-

CO2-

R

R

R

R

R

SCoA

HC

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

malonylCoA

CH3

acetyl CoA

C=O

SCoA

HC

HC-OH

CH2

C=O

C=O

C=O

C=O

C=O

C=O

SACP

SACP

SACP

SACP

SACP

malonyl ACP


Chemical controls
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:

    • Ghrelin- the hunger-stimulating hormone

    • Leptin-the satiety (full-feeling) hormone

    • Glucagon - the stored glucose releasing hormone

    • 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.


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