Day 2 Glucose Metabolism Flashcards

1
Q

GLUT 1 and GLUT 3

A

In all mammalian tissues especially the skeletal muscle and adipose tissue. They allow for glucose uptake into the cell

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2
Q

GLUT 2

A

-Regulate insulin in the pancreas and remove excess glucose from blood in the liver.

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3
Q

GLUT 4

A

Available in the SK muscle and fat cells plasma membrane and their amount increases with endurance training

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4
Q

GLUT 5

A

Located in the small intestines and is primarily a fructose transporter.

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5
Q

Fates of Pyruvate

A
  1. Can undergo oxidative decarboxylation to form acetyl CoA under aerobic conditions and enter the TCA cycle
  2. can be reduced to lactate or ethanol under anaerobic conditions
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6
Q

Formation of lactate

A
  • Under anaerobic conditons lactate dehydrogenase converts pyruvate into lactate which releases an NAD+ that can be used to convert GAP into 1-3 bisphophoglycerate
  • The heart will convert lactate back into pyruvate
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7
Q

Ethanol fermentation

A
  • Formed under anaerobic conditions in yeast.
  • Consist of 2 steps
    1. Decarboxylation of pyruvate to acetyladehyde
    2. Reduction of acetylaldehyde to ethanol
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8
Q

Classic Galactosemia

A

-Mutation in the Gal-1-P-uridyl transferase
results to high intracellular levels of Gal-1-P
-High levels of Gal-1-P can inhibit galactokinase and phosphoglucomutase.

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9
Q

Gal-1-P inhibition of phosphoglucokinase

A
  • Inhibition of this enzyme does not allow Gal-1-P to be converted into Glu-6-P which can enter the glycolytic pathway.
  • Will result in: hypoglycemia, neurological deficit, enlarged liver, jaundice.
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10
Q

Gal-1-P inhibition of Galactokinase

A
  • Inhibiton of this enzyme does not allow galactose to be converted into Gal-1-P
  • Results in high blood serum galactose, cataracts and reducing sugar in urine.
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11
Q

Cataract

A

results from galactose accumulation because of no galactokinase activity. The enzyme aldose reductase will convert galactose into galactitol which leads to water in the lens clouding it.

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12
Q

Non-Classical Galactosemia

A

-Mutation in Galactokinase that results in cataracts and reduced sugar in the urine.

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13
Q

Fructose

A
  • Enters the glycolytic pathway as F-6-P in adipose tissue
  • Enters the glycolysis through the F-1-P pathways as DHAP and GAP when in the liver which bypasses the main regulatory step in glycolysis.
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14
Q

Glyconeogenesis

A

Synthesis of glucose from non carbohydrate sources such as Lactate, Alanine and Glycerol. The 3 irreversible steps must be bypassed.

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15
Q

Pyruvate to Phosphoenol pyruvate

A

two step reaction;

  1. Carboxylation: hydrolyze ATP to carboxylate pyruvate forming OAA (in mitochondria)
  2. Decarboxylation and phosphorylation of OAA (in cytoplasm)
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16
Q

Why are we carboxylating anf decarboxylating?

A

the forward reaction from phosphoenolpyrucvate to pyruvate is an exergonic reation and highly favored so the reverse reaction is endergonic is thermodynamically unfavored. Adding a phosphate group to the pyruvate will form an unstable enol and that is an unfavored endergonic reaction. Having a decarboxylation reaction drives this endergonic reaction forward and lowers the free energy change drastically.

17
Q

Dephosphorylate F-1-6BP

A

hydrolysis of the phosphate by f-1-6-BP’ase which is an allosteric enzyme. this reaction dephosphorylate F-1-6-P to F-6-P.

18
Q

Dephosphorylate G-6-P

A

G-6-P’ase is a liver specific enzyme located in the lumen of the ER membrane that converts G-6-P into free glucose for release into the blood stream. this enzyme also work in glycogen degradation.

19
Q

Regulation of Glycolysis and Gluconeogenesis

A
  • All irreversible steps are regulated but PFK is the primary point of regulation.
  • Can be regulated via allosterism, phosphorylation and transcription
20
Q

Reciprocal regulation

A

allows for highly sensitive allosteric regulation by using ATP

21
Q

Cori cycle

A

the distribution of metabolic burden under anaerobic conditions.

  1. SK muscles go through anaerobic glycolysis +2ATP
  2. Liver induces gluconeogenic pathway with the lactate -6ATP
  3. Heart is also working to convert some lactate for aerobic metabolism
22
Q

Metabolic burden: Muscle

A
  • anaerobic glycolysis

- Glycogenolysis

23
Q

Metabolic burden: Heart

A
  • Aerobic glycolysis

- Glycogenelysis

24
Q

Metabolic burden: Liver

A
  • Gluconeogenesis

- Glycogenolysis

25
Q

Anaerobic glycolysis in Cancer

A

rapid tumor growth leads to poor O vascularization of the tumor. because the tumor is growing so fast it is in need of a lot of energy and has to go through anaerobic glycolysis. the cori cycle will kick in at the expense of the host. eventually the high demand for energy will lead to cancer cachexia (muscle wasting due to starvation)

26
Q

Hypoxia in tumor mass

A
  • Hypoxic environment leads to expression of hypoxia induced transcription factor (HF1)
  • HF1 up regulate proteins for anaerobic metabolism and induce the expression of VEG-F.
  • VEG-F facilitate vascularization of the tumor.
27
Q

Alanine cycle

A

Used under fasting conditions

  • Amino acids supply carbon skeleton for gluconeogenesis this is done by
    1. Transport alanine to liver
    2. De-aminate amino acid via urea cycle
    3. Convert alanine to pyruvate
28
Q

Glycerol

A

Glycerol released from triglyceride degradation is also a precursor for glyconeogenesis

  • enters the gluconeogenetic pathway as DHAP
  • reversible pathway and can produce glycerol for triglyceride synthesis.
29
Q

Pentose Phosphate Pathway

A
  • Produces ribose and NADPH for biosynthetic reactions

- 2 phases : oxidative and non-oxidative

30
Q

NADPH

A
  • Source of electron for reductive biosynthesis

- Acts as an antioxidant for removal of reactive oxygen species

31
Q

NADHP and Glutathione

A
  • Glutathione reduces reactive oxygen species (antioxidant) produced via aerobic metabolism and exogenous sources.
  • Glutathione regeneration dependson NADHP
32
Q

Oxidative Phase

A

oxidize G-6-P to R-5-P in two steps and produce 2 NADPH

33
Q

Nonoxidative Phase

A
  • Carry out a series of Carbon transfers to generate a variety of sugars depending on the cellular needs.
  • utilizes 2 enzymes: transketolase and transadolase for the production og glyvolytic intermediates.
34
Q

Transketolase

A

Transfer 2 carbons fragments from a ketone to an aldehyde

35
Q

Transaldolase

A

Transfer 3 carbon fragments from a ketose to an aldose.