Metabolism

Metabolic pathways

• Conversion of food for energy

• Production of precursors for synthesis
• Storage of food as energy rich fat or
glycogen
• Maintenance of blood glucose levels
• Detoxification of excess amino acids
 Currency of free energy
• ATP + H2O  ADP +pi + H+
• ATP + H20  AMP + ppi + H+

• 7.3 Kcal/mol

• Other nucleotides
• GTP, UTP, CTP
• Other important molecules
– NAD H
• Nicotinamide adenine di nucleotide
– FAD H 2
– Flavin adenine dinucleotide
• Electron donor for reductive biosynthesis
– NADPH
• NADH used manly for generation of ATP
 Carbohydrate metabolism

• Glycolysis
• Pentose phospate pathway
• Cori cycle
• Glycogen lysis
• Krebs, citric acid, TCA cycle
• Oxidative phosphorylation
• Gluconeogenesis
• Glycogen synthesis
Glycolysis is divided
into energy investment
and energy generation
 Coenzyme A

• Carries acyl groups

• Pyruvate makes acetyl CoA to enter Krebs
cycle
– Pyruvate +CoA + NAD+  Acetyl CoA + CO2 + NADH
 Oxidative Phosphorylation

• Need to convert NADH, FAD H2 to ATP

• Use electron carriers to trap energy and link

it to ATP synthase

• Trapped in three complexes

Oxidative phosphorylation

NADH

NADHQ
reductase
 FADH2
QH2
Cytochrome C 1
reductase
Cytochrome C

Cytochrome
oxidase

O2
• NADH  3ATP +NAD

• FADH2  2 ATP +FAD

 Pentose phosphate pathway
• Produces NADPH for synthetic pathways
• produces 5 carbon sugars
• ribose 5 phosphate needed for
– ATP, CoA, NAD, FAD, RNA, DNA
• Linked to glycolysis by transketolase and
transaldolase enzymes
• Controlled by levels of NADP+
C5+ C5 transketolase C3 + |C7

C7 + C3 transaldolase C4 + C6

C5 + C4 transketolase C3 + C6
Glucose –6-phosphate
 NADPH
6 phospogluconate

Ribulose 5 phosphate

Enodiolintermediate
 NADPH
Ribose 5 phosphate

Xylulose 5 phosphate + ribose 5 phosphate


Glyceraldehyde 3 phosphate + sedoheptulose 7 phosphate
 Xylulose 5 phosphate + ribose 5 phosphate


Glyceraldehyde 3 phosphate + sedoheptulose 7 phosphate

Ribulose 5 phosphate  xylulose 5 phosphate

Sedoheptulose 7 phosphate + glyceraldehyde 3 phosphate


Erythose 4 phosphate + fructose 6 phosphate

Xylulose 5 phosphate + erythose 4 phosphate


Glyceraldehyde 3 phosphate and fructose 6 phosphate
 CORI CYCLE

• Glucose in muscle under anaerobic

conditions – exercise
– Converted after glycolysis to lactate to
regenerate NAD+
– Lactate goes to liver
• Reformed to glucose by gluconegenesis
• Returns to muscle and other tissues
 Glycogen Lysis

• Glycogen (n residues) + pi
 Glucose –1-phosphate
+ Glycogen (n-1) residues

Catalysed by glycogen phosphorylase transferase

Glycogen has α 1-4 and α 1-6 bonds
Needs debranching enzyme α 1-6 glucosidase
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Phosphorylase releases glucose 1-p

Transferase moves chain from 1-6 bond to make linear chain
Then α 1-6 glucosidase breaks 1-6 bond
And phosphorylase can release rest of glucose units

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 Fatty acid oxidation
• β oxidation
– Lose 2 carbon length on each cycle

– Produces FADH2, NADH, Acetyl CoA

– Acetyl CoA enters Krebs cycle

– FADH2 NADH enter oxidative phosphorylation
Fatty acid oxidation
Acyl CoA
 FADH2
FAD
Enoyl CoA

H2O 
L hydroxyacyl CoA
 NADH
NAD
Ketoacyl CoA
 Acetyl CoA
CoA=SH
Acyl CoA – 2C
 Oxidation of ketone bodies

D-3-hydroxy butyrate
NAD  NADH
Acetoacetate
Succinyl CoA  Succinate
Acetoacetyl COA
CoA 
2 Acetyl CoA
 Formation of Ketone Bodies

Formed mainly in the liver production of acetone non enzymic

websitehttp://wiki.case.edu/SOM/WebResources
 Protein metabolism
Excess amino acids trans-aminated
then carbon skeletons fed into krebs cyle.
Asparate + α ketoglutyrate

Oxaloacetate + Glutamate

Glutamate  α ketoglutyrate + NH4+

NAD NADH  urea
 Synthetic pathways
• Gluconeogenesis
• Glycogen synthesis
• Fatty acid synthesis
 Glycogen synthesis

Glucose –1-p + Uridine

 UDPglucose + ppi
Then addition of glucose to glycogen chain with
release of UDP.

Storage of energy as glycogen is 97% efficient

• Glycogen synthesis and lysis 2 different
pathways
– Gives better control
– Glycogen stored in liver and muscle, stores are
very limited
 Gluconeogenesis
• Production of glucose from
• Glycerol
• Lactate
• Some amino acids
– Not fatty acids
Lactate  pyruvate  alanine and other amino acids

Oxaloacetate

Phosphoenol pyruvate
 glycerol
2- phosphoglycerate

3 – phosphoglycerate

1,3,diphosphoglycerate

Glyceraldehyde 3 phosphate   dihyroxyacetone phosphate

fructose 1,6 biphosphate

glucose
 Glycolysis and gluconeogenesis

• Have several enzymes in common

• The irreversible ones in glycolysis have
different enzymes in gluconeogenesis
• Pyruvate carboxylase is in mitochondria
• Rest of gluconeogenesis in cytoplasm
• Gives better control
Non essential amino acid synthesis
Protein synthesis

wikipedia
 Fatty acid synthesis
• Synthesis in cytosol
– Oxidation in mitochondria
• In synthesis intermediates linked to malonyl ACP
(CoA) not acetyl CoA
• Enzymes in synthesis complexed together
– Fatty acid synthase
• Synthesis adds 2 carbons at a time
• Reductant is NADPH
• Elongation stops at palmitate
ACP – acyl
carrier protein
 Desaturation of saturated fatty acids

• Desaturation carried out by complex of three

enzymes bound in membranes of mitochondria
• NADH b5 reductase
• Cytochrome b5
• Desaturase
• Mammals cannot insert double bonds before C9
• Therefore need essential n-3 and n-6 fatty acids in
diet
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