Carbohydrate Metabolism

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Created by
Ana Escobedo

Cards (103)

  • Glucose level

    100 mg/dL = 5.6 mM
  • High blood sugar effects
    - long term damage to retina, kidney, blood vessels, nerves
    - urination
    - thirst
    - ketoacidosis
    - blindness
    - heart attack
    - stroke
    - nerve damage
  • Low blood sugar effects
    - autonomic disturbances
    - seizures
    - coma
  • Glucose entry in digestive tract
    - depends on flow of sodium
  • Glucose entry into cell
    - independent of sodium
    - use glucose transporters
  • Glucose transporters

    - GLUT 1
    - GLUT 2
    - GLUT 3
    - GLUT 4
    - GLUT 2, GLUT 4 = most significant = only in specific cells = highly regulated
  • GLUT 2

    - low affinity transporter
    - in hepatocytes = rich in glucose after a meal
    - in pancreatic cells
    - captures excess glucose mainly for storage
    - when glucose is less than Km, it passes through liver and into peripheral circulation
    - Km is high = 15mM
    - in β-islet cells of pancreas with glucokinase = glucose sensor for insulin
  • GLUT 4

    - in adipose
    - in muscle
    - responds to glucose concentration in peripheral blood
    - rate of transport increased with insulin = moves more GLUT 4 to outside membranes
    - Km is close to normal levels = 5mM
  • Muscles store excess glucose as _________
    glycogen
  • Adipose use glucose to form _______
    DHAP = dihydroxyacetone phosphate = converted to glycerol phosphate to store incoming fatty acids as triglycerides
  • Glycolysis

    - only energy-yeilding pathway available for red blood cells = no mitochondria
    - can be done on glucose = main, galactose, or fructose
    - cytoplasmic pathway
    - converts glucose to 2 pyruvate = releases energy
    - energy captured by two substrate level phosphorylation and one oxidation reaction (NADH)
    - also part of process in liver that converts glucose to fatty acid for storage
  • Erythrocytes lack _____________

    - mitochondria
    - glycolysis is done aerobically = lose some energy
  • Skeletal muscle lack ____________
    - access to oxygen
    - glycolysis is done aerobically = lose some energy
  • Important enzymes in glycolysis
    - Hexokinase
    - Glucokinase
    - Phosphofructokinase (PFK1, PFK2)
    - Glyceraldehyde-3-Phosphate Dehydrogenase
    - 3-Phosphoglycerate Kinase
    - Pyruvate Kinase
  • First step of glycolysis

    - intake of glucose via facilitated or active diffuse through GLUT transporter
    - kinase enzyme phosphorylation glucose to glucose 6-phosphate
    - traps glucose inside because GLUT does not recognize glucose 6-phosphate
  • Hexokinase

    - inhibted by glucose 6-phosphate
    - low Km
  • Glucokinase

    - found in liver and pancreatic β-islet cells
    - induced by insulin
    - high Km
  • Phosphofructokinase 1

    - PFK 1
    - rate limiting enzyme
    - fructose 6 phosphate --> fructose 1,6 biphosphate
    - uses ATP
    - inhibited by ATMP and citrate = products of glycolysis = enough energy so stop
    - activated by AMP
    - in hepatocytes, insulin stimulates and glucagon inhibits indirectly by PFK 2 and fructose 2,6 biphosphate
  • Phosphofructokinase 2

    - stimulated by insulin
    - converts very small amount of fructose 1,6 biphosphate to fructose 2,6 biphosphate
    - fructose 2,6 biphosphate stimulates PFK1 = overrides inhibition of PFK1 by ATP to convert glucose to other forms
    - Glucagon inhibits PFK2 and therefore stops fructose 2,6 biphosphate, indirectly inhibiting PFK1
    - found mainly in liver
  • Metabolites of glucose can be made into
    - ATP
    - glycogen
    - fatty acids
    - other storage molecules
  • Rate limiting enzyme for glycolysis
    PFK1
  • Glyceraldehyde-3-Phosphate Dehydrogenase

    - catalyzes oxidation and addition of inorganic phosphate to substrate = glyceraldehyde 3-phosphate
    - makes 1,3 biphosphateglycerate = high energy
    - reduces NAD+ to NADH
  • NADH in aerobic glycolysis

    - can be used by e transport chain
    - provides energy for ATP synthesis by oxidative phosphorylation
  • 3-Phosphoglycerate Kinase

    - transfer phosphate from 1,3 biphosphateglycerate to ADP = make ATP and 3-phsphoglycerate
    - called substrate level phosphorylation
  • Substrate level phosphorylation

    - done by 3-Phosphoglycerate Kinase
    - does not need oxygen
    - only way to make ATP in anaerobic tissue
  • Pyruvate Kinase

    - last enzyme in glycolysis
    - catalyzes substrate level phosphorylation of ADP using phosphoenolpyruvate (PEP)
    - activated by 1,6-biphosphate from PFK1 = feed forward activation
  • Feed forward activation

    - product of an earlier reaction stimulates, or prepares, a later reaction
    - e.g. PFK1 stimulates Pyruvate Kinase
  • Citric acid cycle

    - aka Krebs cycle of TCA (tricaboxylic acid) cycle
    - in mitochondrial matrix
    - main function = oxidize acetyl-CoA to CO2 and H2O
    - produces high energy e carrying molecules = NADH and FADH2
  • Acetyl CoA

    - comes from carbs, fatty acids, and amino acids
  • Pruvate Dehydrogenase complex

    - multi enzyme complex
    - catalyzes uptake of pyruvate via active transport
    - then oxidizes it
    - then decarboxylates it
    - in mitochondrial matrix
    - inhibited by accumulation of acetyl CoA and NADH
  • Carbons as they go from pyruvate to acetyl-CoA
    - 3 carbon pyruvate cleaved = 2 carbon acetyl group and Co2
    - irreversible
    - exergonic ( Delta G = -33.4 kJ/mol)
    - NAD + --> NADH
  • Pruvate Dehydrogenase complex enzymes
    - pyruvate dehydrogenase (PDH)
    - dihydrolpoyl transacetylase
    - Dihydrolipoamide dehydrogenase
    - pyruvate dehydrogenase kinase
    - pyruvate dehydrogenase phophatase
    - first 3 = convert pyruvate to acetyl CoA
    - second 2 = regulate PDH
  • CoenzymeA

    - written as CoA-SH
    - when attaches to pyruvate it attaches at the S = thioester
  • Thioester

    - in acetyl Co-A
    - high energy released when broken = used to drive citric acid
  • PDH

    - pyruvate dehydrogenase
    - pyruvate is oxidized = makes CO2
    - remaining two carbons = bind covalently to thiamine pyrophosphate (vitamin B1, TPP)
    - Mg2+ is needed to function
  • TPP

    - thiamine pyrophosphate
    - aka vitamin B1
    - coenzyme
    - held non covalently to PDH
  • Dihyrolipoyl Transacetylase

    - two carbon bonded to TPP is oxidized and transferred to lipoic acid = coenzyme bonded covalently
    - lipoic acid has disulfide bridge acts as an oxidizing agent which creates the acetyl group
    - acetyl group bound to lipoic acid via thioester linkage
    - Dihyrolipoyl transacetylase catalyzes CoA-SH to replace lipoic acid and transfer acetyl group to form acetyl-CoA
    - lipoic acid left in its reduced form
  • Dihydrolipoyl dehydrogenase

    - FAD is used as coenzyme to reoxidize lipoic acid
    - FAD is reduced to FADH2
    - later, FADH2 is made to FAD while transferring its Hs to NAD+ to make NADH
  • Other ways to produce acetyl-CoA
    - Fatty acid oxidation (β oxidation)
    - Amino acid catabolism
    - Ketones
    - Alcohol
  • Fatty acid oxidation to form acetyl-CoA

    - in intermembrane space
    - activation = tioester bond between carboxyl of fatty acid and CoA-SH
    - goes to intermembrane of mitochondrion BUT fatty acyl cannot pass
    - fatty acyl is transferred to carnitine via a transesterification which moves the acyl group into inner membrane and then transfers to miochondrial CoA-SH
    - so β-oxidation removes two carbon from carboxyl end of acyl-CoA = acetyl-CoA