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2010-11-11 10:48:34
Biomolecular Science

Metabolism (general)
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  1. What is oxidative phosphorylation?
    • Generation of energy as ATP, from ADP, through a sequence of oxidative and reductive chemical reactions which constitute the respiratory chain
    • (aka the electron transport chain, named b/c it is linked to the uptake and use of O2)
    • occurs in the mitochondria
  2. Pyruvate Dehydrogenase complex
    • commiting enzyme
    • commiting step in the oxidative decarboxylation of CHO to either energy (via the TCA cycle) or synthesis of fat from acetly CoA
    • (you CANNOT make glucose from fat)
    • all acetyl CoA is used for energy production or biosnthesis of lipids
    • PDH is a highly regulated enzyme as it controls energy flow into oxidative phosphorylation
  3. Where do tissues get ATP?
    • glucose: the most common fuel (brain is obligate user, other tissues adapt w/ time)
    • Gluamine: lining of the small intestine, lung tissue, others (WBC)
    • short chain fatty acids: lining of the large bowel, ruminants and herbivores in general
  4. Glutamine
    • primary fuel for enterocytes
    • maintains cell integrity
    • maintaining tight junctions
  5. central role of liver in metabolism
    • flow of energy productin nutrients (metabolites)
    • knowing how this scheme works is necessary for diagnosis and treating diabetes, cancer, endocrine disorders and severe infections
  6. protein metabolism: obligate carnivores
    • derive glucose from protein and aa
    • can't down regulate protein metabolism (always ON)
    • unique amino acids needs (arginine)
  7. Diabetes mellitus
    • insulin resistant
    • relative state of hypoglucemis (circluating hyperglycemia)
    • elevated 'stress' hormones (glucagon, adrenaline)
    • bodies attempt to raise intracellular glucose levels
    • negative energy balance incites production of ketone bodies and use of muscle as energy
    • hyperglycemia b/c insulin is ineffective
    • tissues respond to elevated counter regulatory hormones
    • consequences: high BP, mobilization of fatty acids from adipose, high circulating fatty acids (cannot be utilized effectively to TCA cycle, eventually leads to ketosis and ketoacidosis, systemic acidosis, circulatory collapse and death)
  8. lipid metabolism-complex
    • with complex, often confusing terminology
    • clinical issues:
    • how does fat get digested, absorbed and transported in an aqueous environment
    • what happens when it is eaten?
    • what happens when you need to mobilize it for energy?
    • common pathophysiological states?
  9. lipoprotein lipase
    • primary regulator is insulin (activation)
    • found mainly in peripheral tissues, muscle and adipose
    • s
  10. How does fat get out of tissue?
    • hormone sensitive lipase (HSL)
    • activated by lack of insulin and elevated glucagon as well as adrenaline and corisol
    • HSL catalyzes the lipolysis of TG's to free fatty acids and glycerol
    • fatty acids bound to albumin and transported to liver
    • glycerol is a gluconeogenic precursor
  11. Glucose energy in herbivores
    • primary source of glucose is by production in the liver from volatile fatty acids
    • acetate, proprionate, butyrate
    • derived from microbial fermentation
    • foregut (rumen) vs. hindgut (equine)
    • neurohormonal regulation is the same
    • insulin is major regulator in fed state
    • low insulin, high glucagon and others regulate the fasted state
  12. biochemistry of liver function
    • enzymes: ALT (alanine amino transferase), AST (aspertate amino transferase), ALKP (alkaline phosphatase), others (SDH, GGT)
    • bilirubin
  13. ALT
    • transaminase involved in glucose/pyruvate metabolism
    • cytoplasm of liver cells
    • gets into blood when liver cells are dying (indicating liver cell death)
  14. bilirubin
    • metabolite of heme pigments
    • hemoglobin accounts for majority
    • conjugated and excreted in bile
    • yellow color (high levels= jaundice or icterus in tissue or serum and therefore indicates: production in excess of livers capacity to cope, impaired liver FUNCTION, mechanical outflow obstruction)
    • horses and cows normally have yellow serum!
  15. Examples of diseases
    • diabetes mellitus
    • obesity
    • liver disease
    • kidney diseases
    • inherited disorders of metabolism
    • cancer
    • sepsis and severe infections
  16. Metabolism (general)
    • sum of the thousands of enzyme-mediated chemical reactions whereby:
    • energy is extracted from fuels to power motion, biosynthesis and active transport
    • involves many interdependednt metabolic pathways (linear and cyclic)
    • compounds that take part in or are formed are called metabolites
    • catabolic or anabolic reactions
  17. Catabolism
    breakdown of carbon fuels to CO2, H2O and E in form of ATP
  18. Anabolism
    combining small molecules to form complex molecules (proteins and fats) requires E in form of ATP
  19. Stages of catabolism (general)
    • 1) stomach (fats, polysacc, proteins--> fatty acids/glycerol, glucose/sugars, amino acids) no energy produced
    • 2) Acetyl CoA (some energy is produced)- it's an important coenzyme in metabolism b/c it is a carrier of acyl groups
    • 3) TCA cycle, oxidative phosphorylation (most E produced)
  20. Autotrophic
    of or relating to organisms (green plants) that can make complex organic nutritive compounds from simple inorganic sources by photosynthesis
  21. Heterotrophic
    of or relating to organisms which require carbon in organic form, as do all animals (except phytoflagellates), fungi, some algae, parasitic plants, and most bacteria
  22. Free Energy
    • A measure of a system's ability to do work
    • Gibb's free energy, G, is defined by G=H-TS
    • A favorable or spontaneous reaction occurs if the change in free energy is NEGATIVE
    • (exorgenic: giving off energy)
    • (endorgenic: taking in energy)
  23. Metabolic pathways and free energy
    • A thermodynamically or energetically unfavorable rxn can be driven if a favourable rxn is coupled to it
    • metabolic pathways are formed by coupling of enzyme-mediated rxns such that overall free energy change is NEGATIVE
  24. cofactor
    • a nonprotein component essential for notmal catalytic activity of an enzyme
    • may be organic molecules or inorganic ions
    • may activate the enzyme by altering it's shape or participate in the chemical reaction
    • (Ca2+, Mg+, NAD+)
  25. Coenzyme
    • An organic nonprotein molecule that associates with an enzyme in catalysing biochemical reactions
    • usually participate in the substrate-enzymeinteraction by donating or accepting chemical groups
    • many vitamins are precursors of coenzymes (vit B)
  26. Coenzyme A (CoA)
    • A complex organic compound
    • acts in conjunction w/ enzymes involved in biochemical rxns, notably
    • in the oxidation of pyruvate via the krebs cycle and fatty acid oxidation and synthesis
    • comprises pantothenic acid (a B vitamin), adenine (nucleotide) and a ribose-phosphate group
  27. Nicotinamide adenine dinucleotide (NAD+)
    • Coenzyme derived from nicotinic acid (a B vitamin)
    • participates in dehydrogenation rxns
    • loosely bound to enzyme involved
    • normally carries + charge and can accept 1 H atom and 2 e- to become NADH (reduced form)
    • NADH (generated by oxidation of food) gives up 2 electrons (& single proton) to electron transport chain-->NAD+ (oxidised form) + 3 molecules ATP
  28. Biotin
    • the coenzyme for enzymes (propionyl CoA carboxylase) that catalyse the incorporation of CO2 into various compounds
    • the vitamin in the vitamin B complex
    • adequate mounts normally produced by intestinal bacteria
    • other sources include cereals, veggys, milk, and liver
  29. Adenosine triphophate (ATP)
    • Universal currency of free E in biological systems
    • (3P-adenosine-ribose-adenine)
    • large amounts of free E released when ATP is hydrolysed
    • the 2 phosphoanhydride bonds are E rich
    • ATP<-> ADP cycle is fundamental rxn in cells which provides free E to drive rxns
    • ATP turnover very high: ATP molecule consumed w/in 1 min of formation; fairly stable in the absence of a catalyst (only forms as much as needs)
  30. UTP, GTP, CTP
    • some biosynthetic rxns are driven by the hydrolysis of analogues to ATP
    • they are energetically equivalent
    • phosphoryl transfer is a common means of energy coupling
  31. Mechanisms for ATP synthesis (2)
    • 1) high phosphoryl transfer potential compounds can couple carbon oxidation (removal of electrons) to ATP synthesis (substrate-level phosphorylation) can occur in absence of oxygen (anaerobic metabolism) (not very efficient)
    • 2) proton gradient generated by oxidation of carbon fuels accounts for >90% of ATO generation (oxidative phosphorylation)
  32. activated carriers
    • ATP considered an activated carrier of phosphoryl group
    • nicotinamide adenine dinucleotide (NAD+, oxidised form): key electron carrier for the generation of ATP, in substrate oxidation NAD+ accepts 2 electrons and one hydrogen ion/proton (reduced)
    • nicotinamide adenine dinucleotide phosphate (NADP+): key electron carrier in reduction biosynthesis (keytone to fatty acid)
    • Flavin adenine dinucleotide (FAD, oxidised form): an electron carrier in the generation of ATP, in substrate oxidation it accepts 2 electrons and 2 hydrogen ions/protons and becomes reduced
    • coenzyme A (CoA): carrier of activated acyl group. Acyl group linked to CoA by thioester bond to form acyl CoA, key in the sunthesis and oxidation of fatty acids, and oxidation of pyruvate in the citric acid cycle