Metabolic Pathways

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Metabolic Pathways

• Glycogenesis
• Making of glycogen
• Glycogenolysis
• Breakdown of glycogen
• Glycolysis
• Oxidation of glucose
• Hexosemonophosphate shut
• Production of 5-C monosacch NADPH
• Krebs Cycle
• Oxidation of pyruvate acetyl CoA
• Gluconeogenesis
• Making of glucose from noncarbohydrate precursors

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Fig. 4-10, p. 84
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Glycogenesis

• Glucose converted glycogen
• Liver is major site of glycogen synthesis and
  storage
• Other major sites of storage
• Skeletal muscle (more)
• Adipose tissue (less)

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Fig. 4-11a, p. 85
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Fig. 4-11b, p. 85
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Glycogenolysis

• Breakdown of glycogen into individual glucose
  units
• Glucose 1-phosphate
• Regulated
• Glucagon (pancreatic hormone)
• Epinephrine (adrenal medulla)
• Fxn antagonistically to insulin

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Fig. 4-12, p. 86
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Fig. 4-13, p. 87
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Glycolysis

• Metabolic pathway where glucose is degraded into
  2 pyruvate molecules and a triose.
• Next step is cell dependent (aerobic or
  anaerobic).
• Anaerobic lactate conversion.
• Aerobic Krebs cycle (prepared by glycolysis)

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Krebs Cycle

• Also known as the TCA cycle or the
  Embden-Meyerhaff cycle.
• Catabolic
• gt90 of food energy is metabolized via Krebs
• Located in the mitochondria, ETC important.
• 1mol of glu produces 262.8 kcal (38 ATP).

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Lets Review

• Pages 281 - 311.
• Lets discuss the Krebs cycle steps (10).
• Acetyl CoA - produced from beta oxidation, amino
  acid catabolism and GLYCOLYSIS.
• Integral to developing the full potential of
  energy production via the TCA cycle.

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Aerobic Anaerobic Glycolysis

• Anaerobic conditions - NADH to NAD in redxn
  pyruvate to lactate via LDH.
• With new NAD lactate can continue to be produced
  in the absence of O2
• NADH cannot enter the mitochondrion., must be
  reduced. Gets shuttled into the mitochondria.
  Assists in energy production via the ETC (3ATPs
  per mole of NADH).
• Malate and glycerol-3-phosphate are the shuttle
  systems.

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Pentose Phosphate Pathway

• Purpose is to metabolic shunt - generate
  important intermediates not produced in other
  pathways.
• Pentose phosphates necessary for nucleic acids
  (DNA, RNA).
• Reduced NADPH used for biosynthesis of fatty
  acids, assists in cell integrity, drug metabolism
  and reducing substrates in RBC.

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Hexosemonophosphate Shunt

• Involves at least three reactions.
• Mammary glands, adipose, adrenal cortex and the
  liver have great need for NADPH.
• Also active in the thyroid gland an testis but
  not skeletal muscle.
• Pathway involves oxidative and non-oxidative
  reactions.
• Pentoses, fructose-6-phosphate
  glucose-6-phosphate dehydrogenase are the major
  CHO involved in the PPP/HMP.

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Gluconeogenesis

• D-glucose is an essential nutrient for the fxn of
  many cells.
• Glucose can be produced from amino acids,
  lactate, pyruvate and glycerol.
• The process of producing glucose from non-glucose
  sources is gluconeogenesis.
• Question - are carbohydrates essential?

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Gluconeogensis
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Gluconeogenesis

• Essentially this is the reverse of glycolysis.
  Occurs in the liver kidneys.
• This process involves circumventing irreversable
  rxns within glycolysis.
• Turn to the middle of page 96.
• Lets discuss, PEP, malate/aspartate conversion
  to oxaloacetate, use of glucogenic AA.

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Lactate Metabolism

• Effective gluconeogenesis enables the liver and
  body to regulate lactate production during
  physical exertion.
• In muscle and adipose - since no
  glucose-6-phosphate, lactate cannot be
  metabolized into glucose. Thus it accumulates.
• Lactate into glycogen is a taxing and slow
  process.

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Lactate Utilization

• During oxygen debt, lactate accumulates.
• Slowly lactate is shuttled out of the muscle into
  the blood to be delivered to the liver.
• In the liver lactate is converted into glucose.
• What is the name of this cycle? (page 98)
• Question - is lactate accumulation responsible
  for the burn felt during anaerobic exercise?

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CHO Utilization in Exercise
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Glycogenesis Summary

• Glucose use is enhanced when fructose, glycerol,
  lactate are also available.
• Ingested glucose does not automatically become
  glycogen.
• Ingested glucose - RBC uptake - lactate produced
  via glycolysis - hepatic uptake - converted via
  Glu-6-PO4 by gluconeogenesis and than it is
  stored as glycogen.

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Metabolic Regulation

• The body has an ultimate goal of homeostasis - it
  wants catabolism not to out gun anabolism (vice
  versa).
• Example is the classic Rockefeller University
  set-point study.
• Suggest reading the Hirsch paper, early 1990s
  (do a PubMed search).

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Metabolic Regulation

• Modulated by allosteric enzymes or effector
  compounds.
• Hormonal activation via covalent modification or
  enzyme induction.
• Directional shifts in reversible reactions
• Enzyme translocation within a cell.
• Read pages 17 - 19, start at Enzymes.

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Alcohol

• Is ethyl alcohol (ETOH) a carbohydrate?
• Structure CH3-CH2-OH
• Who can tell us how many calories are in a gm of
  ETOH?
• ETOH is metabolized into acetate?acetyl CoA and
  oxidized in the Krebs cycle.
• Most ETOH is metabolized in the liver (cirrhosis)
  and by the enzymes ADH, microsomal ethanol
  oxidizing system (P450) and catalase.

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Alcohol Metabolism

• Discuss energy cost of alcohol metabolism.
• ETOH increases lipid biosynthesis while reducing
  fat oxidation locally (fatty liver, beer gut).

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Carbohydrates in the Diet

• Controversies - high vs. low CHO, glycemic
  index/load, percent actually needed in the diet,
  etc.
• CHOs used in health promotion pre and
  probiotics (ex, types of oligosaccharides - FOS,
  inulin), nutrient timing, resistant starch, and
  fiber (next topic!).

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Fiber

• Origin of human use 1850 (Germany, from animal
  feed).
• The last 25 years have produced much research in
  the areas of dietary and functional fiber.
• Fiber comes from fruit, vegetables, grains, can
  be man made.

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Fiber

• Dietary fiber is non-digestible (CHO, lignans
  intrinsic to plants.
• Functional fiber - isolated non-digestible fiber
  that has been shown to have beneficial
  physiological effects in humans.

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Fiber Plants

• Plant cell wall gt95 of dietary fibers -
  cellulose, hemicellulose, lignan, pectins
  nonstarch polysaccharides.
• Starch also found within plant cells.
• Fruits vegetables provide equal amounts of
  cellulose pectin in the diet.

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Fiber Foods

• Cellulose - bran, legumes, nuts, peas, root
  vegetables, cabbage and the cabbage family.
• Hemicellulose, dietary fiber that is also part of
  plant cell walls.
• Can be water soluble or insoluble.
• Fermented by intestinal microflora.

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Fibers

• Pectin - is also functional. Complex
  polysaccharide. From the primary cell wall of a
  plant. Not a bulking agent. From apples,
  strawberries and citrus fruits, legumes, nuts
  some vegetables.
• Lignin - polymer, insoluble in H20. Also a fxnal
  fiber. From vegetables, wheat and fruits that
  have seeds.

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Fibers cont.

• Gums - hydrocolloid, secretory product from
  injured plants. Exudate. H20 soluble. Many
  sources, also fxnal.
• B-glucan - homopolymer of glucopyranose. From
  cereals (bran/barley can be synthesized from
  yeast. FDA approved for heart health claim.

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Fibers cont.

• Fructans - inulin, oligosaccharides, FOS.
  Prebiotic. ? bifidobacteria.
• Resistant starch - non-digestible. ? butyrate
  formation (SCFA).
• Chitin/chitosan - amino-polysaccharide.
  Insoluble, extract from crustaceans, may also
  lower Tchol.

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Fibers cont.

• Polydextrose/polols - glucose-sorbitolunits that
  are polymerized. Used as a bulking agent. Can
  cause gastric distress.
• Psyllium - husk extract from plantago. High H20
  binding property - bulking agent, think
  Metamucil.
• Resistant dextrins - resistant maltodextrin from
  heating cornstarch tx with amylase.Functional,
  similar to B-glucan.

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GI response to soluble/insoluble fiber.
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Solubility

• Fibers that dissolves in hot water is soluble.
• Fiber that does not dissolveis not soluble.
• Insoluble fiber enhance GI transit time fecal
  bulk.
• Soluble fibers delay gastric emptying.
• Vegetables, wheats some grains insoluble gt
  soluble fiber.

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Soluble Effects

• GI delayed emptying, interference with nutrient
  absorption, reduced enzyme fxn, attenuation of
  blood glucose response, altered transit time.
• Diminished absorption of lipids - ? Tchol, ? bile
  excretion, may enhance mineral absorption (ex
  calcium).

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Fermented Fibers

• Enhance the microflora of the GI tract.
• Produces lactate, butyrate and other SCFAs. Also
  produces CO2 methane gases.
• Effects - ? H2O and NA absorption, stimulates
  mucosal cells, provides some energy, acidifies
  the lumen (may protect against colon Ca).

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Nonfermentable Fibers

• Cellulose, lignan, hemicellulose. Acts as a
  detoxifying bulking agent.
• May ? conversion of procarcinogins to carcinogens
  via colonic bacteria enhancement.
• Rice bran gt wheat bran. Cellulose, psyllium,
  inulin and oligosaccharides also increase fecal
  bulk.

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Fiber Recommendations

• 2002 National Academy of Sciences recommended for
  men 19 to 50 38gm/total/day for females 19 to
  50 25 gm/total/day.
• In general from age 1 onward, we should be
  getting 19 gm/day and this ?s as we age to 25 to
  38 gm/d.

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Fiber Guidance

• To meet the needs, eat fiber-rich legumes (also a
  source of protein), at least 5 svgs of fruit
  vegetables and at least 2-3 servings/d of whole
  grains as part of the 6 to 11 servings
  recommended by the Food Guide Pyramid
  (www.mypyramid.gov)

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Fiber Take Home

• We do not eat enough.
• Why?
• How can we as healthcare professionals affect
  change?
• Will this ? disease incidence?
• Food first, functional foods second, supplements
  third. Teach lifestyle.