Metabolism Flashcards
What are the central pathways of energy metabolism?
• Glycolysis
• Citric acid cycle (aka Krebs cycle, TCA cycle)
• Electron transport/oxidative phosphorylation
• Fatty acid oxidation (aka β-oxidation)
• Gluconeogenesis
• Fatty acid synthesis
• Photosynthesis
• (Amino acids and nucleotides synthesized by non-central pathways; degradation funnels intermediates into central pathways)
• In aerobic organisms, all pathways funnel into citric acid cycle
What are the cellular location of major metabolic pathways?
What are the main steps of respiration?
- Glycolysis – the simple sugar glucose is broken down in the
cytosol - Pyruvate, the product from glycolysis, is transformed into
acetyl CoA in the mitochondria in preparation for the next step - The citric acid cycle - where electron carriers, NADH and
FADH2, are made in the mitochondria - Oxidative phosphorylation – this process occurs in the
mitochondria, and uses the electron transport chain to produce ATP, the bulk of usable energy for the cell
Glycolysis vs gluconeogenesis
- This reversal of glycolysis is gluconeogenesis
- Instead of using carbohydrates to produce glucose, our body converts non-carbohydrate sources (like amino acids) in our liver into glucose
- Our body then takes that glucose and uses it to maintain our blood sugar at a constant, healthy level
What happens in glycolysis?
What are the 4 fates of pyruvate?
What happens in the citric cycle?
What happens in oxidative phosphorylation?
What happens in gluconeogenesis?
What does the rate of a biochemical reaction depend on?
- Concentration of reactants versus products
- Activity of the catalyst
– concentration of the enzyme
– rate of translation versus rate of degradation
– intrinsic activity of the enzyme
– could depend on substrate, effectors, or phosphorylation state - Concentrations of effectors
– allosteric regulators
– competing substrates
– pH, ionic environment - Temperature
How does temperature affect rate of reaction?
- For human metabolism the optimal temperature is 36.8°C
- Increasing temperature increases the Kinetic Energy that molecules possess. In a fluid, this means that there are more random collisions between molecules per unit time. Since enzymes catalyse reactions by randomly colliding with substrate molecules, increasing temperature increases the rate of reaction, forming more product.
- However, increasing temperature also increases the vibrational Energy that molecules have, specifically in this case enzyme molecules, which
puts strain on the bonds that hold them together. - As temperature increases, more bonds, especially the weaker Hydrogen and Ionic bonds, will break as a result of this strain. Breaking bonds within the enzyme will cause the Active Site to change shape.
- This change in shape means that the Active Site is less Complementary to the shape of the Substrate, so that it is less likely to catalyse the reaction. Eventually, the enzyme will become Denatured and will no longer function. As temperature increases, more enzymes’ molecules’ Active Sites’ shapes will be less Complementary to the shape of their Substrate, and more enzymes will be Denatured. This will decrease the rate of reaction
How does concentration affect rate of reaction?
- The rate is more sensitive to concentration at low concentrations
- Chemical kinetics: the frequency of substrate meeting the enzyme matters
- The rate becomes insensitive at high substrate concentrations
- The enzyme is nearly saturated with substrate
What is the role of AMP-activated protein kinase (AMPK) in carbohydrate and fat metabolism?
• AMPK is activated by elevated [AMP] or decreased [ATP], by exercise, by the sympathetic nervous system (SNS), or by peptide hormones produced in adipose tissue (leptin and adiponectin)
• When activated, AMPK phosphorylates target proteins:
Ø shifts metabolism in a variety of tissues away from energy-consuming processes such as the synthesis of glycogen, fatty acids, and cholesterol
Ø shifts metabolism in extrahepatic tissues to the use of fatty acids as a fuel
Ø triggers gluconeogenesis in the liver to provide glucose for the brain
• In the hypothalamus, AMPK stimulates feeding behaviour to provide more dietary fuel
What are appropriate targets for glycolytic flux?
- Hexokinase and phosphofructokinase are appropriate targets for
regulation of glycolytic flux
• Increased hexokinase activity enables activation of glucose
• Increased phosphofructokinase-1 activity enables catabolism of activated glucose via glycolysis - Hexokinase affects flux through glycolysis more than
phosphofructokinase
What are the isozymes of hexokinase?
- HK I is expressed in all tissues, to different levels
- HK IV (e.g., glucokinase) is only expressed in the liver:
• has higher Km, so responsive to higher [glucose]
• not inhibited by glucose-6-phosphate, so can function at higher [glucose]
• functions to clear blood glucose at higher [glucose] for storage as glycogen - Isozymes are different enzymes that catalyze the same reaction:
• typically share similar sequences
• may have different kinetic properties
• can be regulated differently
The protein inhibitor of hexokinase IV is a nuclear binding protein that draws hexokinase IV into the nucleus when the fructose 6-phosphate concentration in liver is high and releases it to the cytosol when the glucose concentration is high
What is the regulation of phosphofructokinase-1?
What are the conditions for gluconeogenesis vs glycolysis?
