Download Metabolism Basics

Metabolism Basics
Two faces of metabolism
• Catabolism - degradation
• Anabolism - biosynthesis
Catabolism
• Catabolic sequences yield energy
– ATP, NADH
Oxidizable
• Oxidative substrate (glucose)
+
NAD
H2O
Oxidized
product (CO2)
NADH
ATP
O2
Catabolic Pathways
•
•
•
•
Glycolysis
TCA (Krebs) cycle
-oxidation of fatty acids
Oxidation of -keto acids
(from amino acids)
• Hexose monophosphate
path
• Oxidative
phosphorylation
• Photophosphorylation
ATP, NADH
GTP, NADH, FADH2
NADH, FADH2
NADH, FADH2
NADPH
ATP
ATP, NADPH
Catabolism
is
Convergent
Carbohydrates Fats Proteins
Acetyl-CoA
Krebs
cycle
NADH,
FADH 2
O2
ATP
Catabolic Regulation
• Allosteric
• Covalent
• Hormonal
• Altered gene
expression
ATP and PFK-1
Phosphorylation of glycogen
phosphorylase
Epinephrine

[cAMP]

Protein phosphorylation
AA oxidizing enzymes
Localization of Catabolism
• Mitochondria (matrix, membrane)
– -oxidation
– AA oxidation
– Pyruvate oxidation
– Oxidative phosphorylation
Localization of Catabolism
• Cytosol
–Glycolysis
–Hexose-P
• Chloroplast
–Photophosphorylation
Compartmentation of Catabolism
Cytosol
Mito
Fatty acids
ATP
ADP
CoASH
NADH
Separate pools
CoASH
NADH
Tissue Specialization in
Catabolism
• Glycolysis
• Krebs Cycle
Every Cell
Almost every cell
(not RBC)
• Fatty acid oxidation Most tissues (not
brain)
Liver
• Urea cycle
• -keto acid oxidation Liver (except
branched chains)
Irreversibility of Catabolism
Exergonic
Glucose
38 (ADP+Pi)
o
²G '
CO2 + H2O -2840 kJ/mol
38 ATP
+1160 kJ/mol
Overall: -1680 kJ/mol
o
Irreversible
-²G ' /RT 670
Keq = e
=e
=Very large!
Summary: Catabolism
•
•
•
•
Oxidative
Convergent
Tightly regulated
Localized intracellularly
– Separate pools
• Tissue-specific
• Universal
• “Irreversible”
– Exergonic
Anabolism (Biosynthesis)
• Reductive
CO2 + [H]
CHO
O
H3C C
CH2 CH2
O
• Cofactor: usually NADPH
– Pentose-P pathway
– Glutamate dehydrogenase
– Photosynthetic electron transfer
– NADH + NADP+
NAD+ + NADPH
Transhydrogenase
Anabolism:Estradiol
Divergent
Aldosterone
Bile
acids
Cortisol
Cholesterol
Vit A
Dolichols
Phospholipids
Eicosanoids
Vit D
Triglycerides
Fatty acids
CoQ
Isopentenyl-PP
Acetyl-CoA
Anabolism: Regulation
Glutamate
Glutamine
Tryptophan
Histidine
Complex
"Feedback"
Inhibition
Carbamyl-P
Glucosamine
CTP AMP
Anabolism: Localization in Cells
• Gluconeogenesis
• Fatty acid
synthesis
• Glycogen
synthesis
• Starch synthesis
• Amino acid
synthesis
Cytosol (mainly)
Cytosol
(Chloroplasts)
Cytosol
Chloroplast
Cytosol
Distinct pools:
In mitos: [NAD+]/[NADH] high
In cytosol: [NADPH]/[NADP+] high
Anabolism: Tissue-Specific
• Gluconeogenesis
Liver (kidney)
• Fatty acid synthesis Liver, mammary gland
• Steroid hormones Adrenal cortex, ovaries,
testes
• Glycogen synthesis Muscle, liver
• Vitamins
No tissue; thus
required in diet
Anabolism: “Irreversible”
O
C
CoAS
CH3 + HCO3
ATP
–
–30.5 kJ/mol
ADP + Pi
O
O
C CH2 C
O
SCoA
Malonyl-CoA
ATP hydrolysis shifts the
equilibrium towards the product
Two Separate Pathways
Catabolic path  Anabolic path
Reciprocal Regulation
• Anabolic and catabolic pathways are
reciprocally regulated
• Regulation occurs at reactions unique to
the path
• Same regulator has opposite effect on
path
– Epinephrine
• Stimulates -oxidation
• Inhibits fatty acid synthesis
Summary: Anabolism
• Reductive (NADPH)
• Divergent
• Regulated
– At branch points
– Reciprocally with catabolism
• Localized
– Generally in the cytosol
Summary: Anabolism
• Tissue-specific
–Liver
• “Irreversible”
–Use of ATP
• Separate path from catabolism