Metabolism Flashcards
Definition of metabolism and common diseases involving it:
All chemical reactions that maintain the living state of cells and organisms
Common diseases involving metabolism:
- Diabetes
- Obesity
- Cancer
Features of metabolism
Redox reactions:
- Oxidised: loses electrons
- Reduced: gains electrons
Electron carriers:
- NADPH + H+
- NADH + H+
Glucose oxidises to CO2 and H2O
Stages of catabolism of fuel molecules
Glucose:
1. Glucose enters cells
2. Acetyl-CoA production
3. Acetyl-CoA oxidation
4. Electron transfer and oxidative phosphorylation
Structure and functions of major carbohydrates
Glucose:
- 6 carbons
- OH on carbon 1
ATP:
- Three phosphate groups
- One ribose sugar
- One base
How is glucose transported into the cell?
Via:
- Na+/glucose symporters
- Passive facilitated diffusion glucose transporters
Describe glycolysis and name its central intermediate compounds:
Steps:
1. Glucose trapped and destabilised
2. Aldolase generates 2 inter convertible three-carbon molecules
3. Generation of ATP
Compounds:
1. Glucose > fructose-1,6-bisphosphate via 2 ATP
2. Fructose-1, 6-bisphosphate > 2x triose phosphates
3. 2x triose phosphate > 2x pyruvate via via 4 ADP and 2 NAD+
Summary:
Glucose + 2ADP + 2Pi + 2NAD+ —> 2pyruvate + 4ATP + 2H2O + 2NADH + 2H+
Key regulatory mechanisms of phosphofructokinase:
Activated by AMP
- Increases glycolysis when energy is needed
Inhibited by:
- ATP: Slows glycolysis when energy is abundant
- Citrate: Slows pyruvate energy to TCA cycle
- H+: Slows glycolysis if too much lactic acid produced
Anabolism and catabolism
Anabolism: Assembling of molecules - required energy
Catabolism: Breaking down of molecules to yield energy
Lactic acid system:
NADH used to ferment pyruvate to lactic acid
NADH regenerated at beginning of stage 3 of glycolysis
Cancer and glycolysis
The Warburg Effect:
Cancer cells produce energy by high rate of glucose metabolism to lactate
Treating cancer:
- 2-deoxygenated-glucose blocks breakdown of G6P
- 3-bromopyruvate blocks production of 1,3 bisphosphoglycerate
- Dichloroacetate promotes conversion of lactic acid to pyruvate
Importance of regenerating NAD+
Limited amounts present in cell
NADH must be re-oxidised to NAD+ or glycolysis cannot continue
Regenerated in final stage of glucose catabolism - electron transport chain
TCA cycle reactions
Six-carbon unit decarboxylated twice yielding CO2
Four oxidation reactions yields NADH + H+ and FADH2
One GTP formed
4 carbon unit recreated
TCA cycle location
Mitochondrial matrix
Exception: Succinate dehydrogenase is in mitochondrial membrane
Control in TCA cycle:
High ATP, NADH and acetyl-CoA means plenty of energy
High ADP and NAD+ means lack of energy
High succinyl-CoA and acetyl-CoA means plenty of precursor molecules for biosynthetic reactions
Pyruvate in aerobic conditions:
Glycolysis
TCA cycle/PDC:
- Enters mitochondrial matrix via pyruvate transporter (facilitated diffusion)
PDC:
1. Pyruvate loses CO2 and HETPP is formed
2. Hydroxyethyl group transferred to lipoic acid and oxidised to form acetyl dihydrolipoamide
3. Acetyl group transferred to CoA
4. Dihydrolipoamide reoxidised
Pyruvate in anaerobic conditions:
Ketone body formation:
- Acetyl CoA diverted to ketones
Oxaloacetate consumed for gluconeogenesis
Fatty acids oxidised to provide energy in absence of glucose
Disorders
PDC Deficiency:
- Neurological diastase in children
HLRCC:
- Multiple systematic benign and malignant tumours
Electron transport chain
- Electrons from NADH and FADH2 reduce O2 to H2O
- Energy of electron transport pumps protons (H+) from mitochondrial matrix to inter membrane space
- Protons flow back across membrane through transporter linked to ATP synthase down conc. gradient
- Energy of proton flow phosphorylates ADP to ATP
Activation of ATP synthase:
Flow of protons turn rotor causing conformational change
ATP synthase structure in the mitochondrion:
F1 subunit in mitochondrial matrix
F0 subunit - hydrophobic, in inner membrane
Stator: a, b, alpha, beta _ subunits
Rotor: c, gamma, _ subunits
Sources of ATP generation:
NADH is energy source:
- NADH/FADH2 from TCA made in matrix
- Cannot cross inner mitochondrial membrane
- Shuttles allow energy to be coupled to ATP generators
Links between glycolysis, the TCA cycle, and oxidative phosphorylation
2NADH from glycolysis = 1.5 ATP
2NADH from oxidative phosphorylation = 2.5 ATP
2FADH2 = 1.5 ATP
6NADH from citric acid cycle = 2.5 ATP
