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Biochemistry KCUMB > AZDI biochem quiz 2 > Flashcards

AZDI biochem quiz 2 Flashcards

1
Q

What is the general view on glycolysis?

A
  • glucose metabolism that generates ATP
  • Glucose is metabolized into lactate w/o Oxygen
  • In an oxygen adequate system, glucose is metabolized more effeciently to CO2 and H2O
  • Sequence of reactions
    • 1 molecule of glucose in to 2 molecules of pyruvate and generates 2 ATP
    • ANAerobic process (THAT IS WITHOUT OXYGEN)
  • Pyruvate will late be completely be oxidized under aerobic conditions, generating much more ATP,
    *
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2
Q

What are characteristics to glucose as it relates to glycolsis ?

A
  • GLucose is a common and important fuel
  • in mamamels
    • glucose is only fuel that the brain uses under conditions of non starvation
    • glucose is the only fuel that red blood cells can use
  • pyruvate and lactate can be salvaged and resynthesized to glucose via gluconeognesis
  • SOURCES of glucose in diet
    • disaccharides especially
      • especially sucrose and alctose
    • starch
    • glycogen
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3
Q

Which is more effecent the anaerobic processing of glucose of the aerobic processing of pyruvate?/

A

PYRUVATE complete oxidation is more effecient that anaerobic glycolysis

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4
Q

How does glucose uptake occur

A
  • Hepatic portal vein takes nutrients rich blood to liver
  • liver process this extremely blood
  • glucose uptake occurs via protein transporters called glucose transporters (GLUTs)
    Many different types
  • GLUT 1
    • Ubiquitous but expressed highly in brain and RBCs
      • high affinty for glucose
  • GLUT 2
    • MAIN transporter in liver
      • Low affinty for glucose
  • GLUT 3
    • Main transporter in neurons
      • high affinty for glucose
  • GLUT 4
    • Present in skeletal muscle, heart, adipose tissue
      • insulin dependent
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5
Q

What are the characteristics of the glucose transporters (GLUTS)?

A
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6
Q

What is the overview glycolsis ?

A

Location: occurs in the cytoplasm of eukaryotic cells

Glycolysis divided into 2 stages

  1. trapping of glucose and its cleavage into 2 interconvertable 3 carbon molecules
    1. trapping is done by adding a phospahte onto glucose
  2. Generation of ATP
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7
Q

Howd oes glycolysis begins?

A
  • The first stage of glycolysis begins with the phosphorylation of glucose by hexokinase
  • then follows with the isomerization of dihydroxy acetone phosphate to glyceraldhyde 3 phosphate
  • G3p and HAP are the same molcule btw
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8
Q

How can the first stage of glycolysis be broken up?

A
  • into 5 steps
  • trapping of glucose and preparation phase
    • no atp generated
    • two ATP consumed
  • Consists of three reactions: phopshorylation, isomerization, a second phosphorylation
  • Strategy of this phase is to trap the glucose in cell and form a compound that can be readily cleaved unto 2 phosphorylated three carbon units
    • PYRUVATE
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9
Q

What is the first step in stage 1 of glycolysis ?

A
  • Glucose phosphorylated to glucose-6-phosphate (G6P)
  • ATP is used up
  • HEXOKINASE (in all tissues) and GLUCOKINASE (in liver) are the ENZYMES
    *
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10
Q

What is thesecond step in the first stage of glycolsis ?

A

G6P is isomerized to fructose-6-phosphate (F6P )

ENZYME = PHOSPHO-glucose-ISOMERASE

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11
Q

What is the third stepp of the first stage of glycolysis?

A
  • F6P phosphorylated to fructose-1,6-bisphate (F1,6 BP)
  • ATP IS CONSUMED
  • ENZYME = PHOSPHOFRUCTOKINASE
    • THIS IS THE RATE LIMITING ENZYME OF GLYCOLYSIS
  • RATE LIMITING STEP
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12
Q

What is the fourth step of the first stage of glycolysis ?

A

F1,6BP is broken down to glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phospahte (DHAP)

ENZYME = ALDOLASE

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13
Q

What is the fifth step of the first stage of glycolsis ?

A

DHAP (dihydroxy acetone phosphate) is isomerized to G3P.

ENZYME = triose phospahte isomerase

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14
Q

What is the second stage of glycosis ?

A

where energy is harnessed in GAP (glyceraldhyde-3-phosphate) used to form ATP

has 3 major steps

  1. GAPDH step
  2. Phosphoglycerate kinase/mutase step
  3. Enolase/Pyruvate Kinase step
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15
Q

WHat is the first step of the second stage of glycolysis

A
  • GAPDH STEP
  • OXidative phosphorylation of GAP (glyceraldhyde 3 phospahte) to form 1 , 3 - BPG (1 , 3 - bisphosphoglycerate)
    • 1, 3 BPG has a high phosphoryl transfer potentia
      ​
  • REDUCES NAD+ to NADH
    • NADH contains a Pair of high energy eletrons
      • sent to eletron transport chain (ETC), play a role in oxidative Phosporylation (OXPHOS )
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16
Q

What is the second step of the second stage of glycolysis ?

A
  • Phosphoglycerate Kinase Mutatase STEP
  • The kinase converts 1, 3 BPG to 3 PG (3-phosphoglycerate)
  • ADP is phopshorylated to ATP to form 3-FG
    • via substrate transfer
  • the mutase moves phospahte from 3rd to 2nd postion (2 PG)
  • remember this happens 2x
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17
Q

What is the third step the second stage of glycolysis ?

A
  • ENOLAE/PYRUVATE KINASE STEP
  • dehydration of 2 PG by enolase forms PEP (phoshpoenolpyruvate) , an ENOL with HIGH phosphoryl transfer potential (Unstable)
  • Then, pyruvate kunase transfers phosphoryl group from PEP to ADP to form ATP
    • PEP is converted from unstable enol to pyruvate a stable ketone
    • THis step is irreversible
  • THIS STEP HAPPENS TWICE
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18
Q

What are the ten steps or reactions that occur in glycolysis?

A
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19
Q

WHat is the fate of pyruvate?

A
  • Pyruvate can be reduced to lactate, with the regeneration of NAD+
  • Pyruvate can be oxidaized aerobically via the citric acid cycl after first undergoing an oxidative decarboxylation to form acetyl CoA
  • Yeast and some other micro-organisms can convert pyruvate to ethanol
    • maintain redox balance
  • RBC convert pyruvate to lactate for energy
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20
Q

GAP eventual conversion to PEP converts NAD+ to NADPH, how is this step counteracted?

A

During anaerobic interactions, Pyruvate becomes latate which done via the converstion of NADH to NAD+

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21
Q

How does fructose and galactose enter the glycolsis ?

A
  • sucrose is dissacchride of glucose and fructose
  • Lactose is a disaccharide of glucose and galactose
  • Fructose and galactose are converted into glycolytic intermediates
  • this bipasses phosphorfructose kinases
  • Fructose quickly turned to fat times of high energy
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22
Q

How is fructose metabolized ?

A
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23
Q

How is galactose metabolized

A
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24
Q

How glycolysis regulated?

A

major regulatory enzymes

  • hexokinase
  • phosphofructokinase
  • pyruvate kinase
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25
Q

How id glycolysis regulated in muscles?

A
  • Remember that hte goal sis to generate ATP during activity
  • ATP levels regualte glycolysis
  • a high ratio of ATP/AMP while rest prevents Pyruvate kinase from converting PEP to pyruvate and F6P from becoming F1,6-BP
  • While during excercise, the demand for ATP is high and thus decreasing the the rate of ATP to AMP and releasing the inhibtory control of pyruvate kianse
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26
Q

How is glycolysis regulated in the liver?

A
  • Goal: to maintain blood glucose levels
  • to provide building blocks for other pathways (in resposne to biochemical diversity and need)
  • Phosphofructokinase
    • Activated by F-2,6- BP
    • Inhibtited by citrate
  • Glucokinase
    • no Hexokinase in liver
    • Glucokinase is not inhibited by glucose 6-phosphate- glucose permanently trapped
  • Pyruvate Kinase is regulated by allosteric effectors and covalent modification
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27
Q

how does the activity of glucokinase and hexokinase compare to one another?

A
  • Glucokinase
    • activty and blood glucose
      • low = inhibition and dont want to trap glucose
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28
Q

WHat can an excess of fructose lead to?

A
  • fructose (like high cructose corn syrup)
    • linked to fatty liver insulin insensitivity, obesity, and ttype 2 diabetes
  • THese disorders not result of simple excess energy consumption but rather how fructose is processde by the iver
  • actions of fructokinase and triose kinase bypass the most important regulatory step in glycolysis, the phosphofrutokinase-cataylzed reactions
  • fructose dervied G3P and DHAP are processed by glycolysis to pyruvate and acetyl CoA in an unregulated Fashion
  • Excess acetyl CoA converted to Fatty acids, which can be transported to adipose tissue to form triacylglycerols resulting in obesity
  • Liver also begins to accumulate fatty acid, resulting in fatty liver
  • activity of the fructokinase and triose kinse can deplete the liver of ATP and inorganic phosphate, comprising liver functions
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29
Q

What are the characteristics of Lactose intolerance

A

INability to metabolize lactose

Drinking milk causes disturbances in GI functions

caused by deficiency in enzyme lactase (which breaks down lactose to glucose and glactose)

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30
Q

What are characteristics of galactose metabolism defects

A
  • Disruption of galactose metabolism is called galactosemis
  • classic galactosemia (most common form) is an inheirted deficiency in galctose 1-phosphate uridyl transferase activity
  • symptoms
    • Vomiting/ diarrrhea after consuming milk
    • enlargemnt of liver and jaundice, sometimes progressing o cirrhosis
    • cataracts in eyes
    • lethargy and retarded mental development
    • significant elevation of blood falactose levels, and presence of galactose in urine
  • Diagnostic criteron : absence of the transferase in RBC
  • Treatment: remove galactose (and lactose ) from diet
  • Although elimination of glactose from diet prevents liver disease and cataracts development, majority of patients still suffer from central nervous system malfunction most commonly a delayed acqusition of language skills
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31
Q

What is cataracts?

A
  • Cataracts is the clouding of the normally clear lens of the eye. If the transferase is not active in the lens of the eye, the presence of aldose reductase causes the accumulation galactose to be reduced galactitol
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32
Q

how do tumors relate to glycolysis ?

A
  • Tumors display enhance rates of glucose uptake and glycolysis
  • rapidly growing tumor cells metabolize glucose to alctate even in the presence of oxygen, a process called aerobic glycolysis or the warburg effect
  • tumors with a high glucose uptake are particularly aggressive, and the cancer is likely to have poor prognosis
  • visualization of tumor and effectiveness of treatment:
    • A nonmetabolizable glucose analog, 2-18F-2-D-deoxyglucose, detected by a combination of positron emission tomographu (PET_ and computer aidsed tomogrpahy (CAT)
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33
Q

Which of the following glucose transporters is the main transporter in the liver ?

A. GLUT 1

B. GLUT 2

C. GLUT 3

D. GLUT 4

E GLUT 5

A

GLUT 2

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34
Q

WHich of the following enzymes is the most important regualtor of glycolysis ?

A. hexokinase

B. Phosphoglucose Isomerase

C. PhosphofructoKinase

D. Glyceraldehyde-3-phosphate dehydrogenase

E. Pyruvate Kinase

A

PHOSPHOFRUCTOKINASE

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35
Q

WHich of the following is not an intermediate in the glycolyti pathway?

A. 3 Phosphoglycerate
B. Fructose 1,6- Bisphosphate
C. Glucose 1-Phosphate
D Glyceraldehyde 3-Phosphate
E PhosphoenolPyruvate

A

GLUCOSE 1-PHOSPHATE

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36
Q

What are characterisitcs of gluconeogenesis?

A
  • occurs in liver and kidney
  • synthesis of glucose from non-carbohdrate precursors
  • pathway not a reversal of glycolysis
  • Pathway converts pyruvate into glucose
  • No ATP made. It is only comsumed
  • Major precursors are lactate, amino acids, and glycerol
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37
Q

What steps the irreversible steps of glyolysis replaced by in gluconeogensis ?

A
  • pyruvate carvoxylase
  • Phosphoenolpyruvate carboxykinase
  • fructose 1,6-bisphosphatase
  • Glucose 6-phosphatase
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38
Q

How do gluconeogenesis compares to glycolysis ?

A
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39
Q

How does the shuttling of OAA occur?

A
  • PC is a mitochondrial enzyme
  • other enzymes of gluconeogenesis found in cytoplasm
  • OAA (product of PC) transported to cytoplasm via malate suttle
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40
Q

how is glyceraldhyde 3 phosphate converted to glucose?

A
41
Q

How is pyruvate converted to Glyceraldhyde 3- phosphate

A
42
Q

what proteins are involved in shuttling G6P -> glucose across the plasma membrane

A
  • Enzyme located in the lumen of the endoplasmic reticulum
  • T1 = transports glucose 6-phosphate to ER
  • T2 = transports inorganic phosphate back into cytosol
  • T3 = transports glucose back into cytoplasm
43
Q

Be able to match enzyme and reactions

A
44
Q

Where does ATP processing occuring in glycolsysis and compare that to guconeogensis.

A
  • Glycolysis generates ATP
  • Gluconeogenesis consumes ATP
  • Energy charge (ATP/ADP ratio) which pathway will be most active
  • Gluconeogenesis and glycolysis are reciprocally regulated
45
Q

how does regulation of hgycolysis and gluconeogenesis in the liver?

A
  • in the liver, rates of glycolysis and glucogenesis are adjusted to maintain blood glucose
  • fructose 2, 6- nisphosphate strongly stimulates phosphofructokinase and inhibits fructose 1, 6-bisphosphatase
  • Two enyzmes regulate the oncetration of fructose 2,6 bisphosphate: phosphofructolinase 2 (PFK2) and fructose bisphosphatase 2 (FBPase2)

insulin inhibts FBPase2 and stimulates PFK2 while glucagon does the opposite

46
Q

What is the cori cycle?

A

Lactate produced in skeletal muscle and RBC can be converted back to pyruvate in the liver

THe pyruvate can enter the gluconeogenic pathway and regenerate glucose (which was the source of lactate)

47
Q
A
48
Q
A

Oxaloacetate

49
Q
A

FRuctose 1,6 Bisphosphatase

50
Q
A

Lactate

51
Q
A
52
Q

WHat is the structure of glycogen?

A
  • Glycogen is a long chain homopolymer of glucose molecule with branches
  • Glucose molecules within chain linked via alpha-1,4, glycosidic bonds
  • Branch points formed via alpha 1,6 glycosidic bonds between glucose monomers of seperate chains
  • non-reducing ends each contain a terminal glucose with a free hydroxyl group at carbon 4
  • reducing end consists of glucose monomer connected to a protein called glycogenin
  • Glycogenin creates a short glycogen polymer on it self and serves as a primer for glycogen synthesis
  • gylcogen is degraded and extended for non reducing end
53
Q

where does glycogen storage occur

A
  • glycogen storage in liver, muscle, and other tissues
  • Stored as granules
  • Granules contain not only glycogen but also the enzymes needed for glycogen metabolism
  • defects in these enzymes can lead to disorders
54
Q

What is the function of glycogen ?

A

Liver glycogen = regualtes bood glucose levels

muscle glycogen = provides reservoir of fuel (glucose) for physical activity

55
Q

What are the general characteristics of glycogen metabolism?

A
  • Regulated storage and release of glucose
  • synthesis and degradation of glyogen involve different pathways
    • glycogenesis = glucogen synthesis
    • Glycogenolysis = glycogen degradation
  • both pathways regulated independently
  • regulation
    • Allosteric control
    • covalent modification through reversible phosphorylation of key enzymes
    • Hormonal control
56
Q

What is glycogenesis?

A

Glycogen synthesis

57
Q

Wha tis the first key step in glycogenesis ?

A

trapping and activation of glucose

  • glucoskinase / hexakinase
    • in cytosol of hepatocytes and muscle cells catalyze phosphorylation of glucose to glucose 6 phosphate
    • TRAPS the GLUCOSE IN CELL
  • Phosphoglucomutase then reversible isomerizes glucose-6-phosphate to glucose -1-phosphate
  • URdine diphosphate (UDP)- glucose pyrophosporylase then transfers the glcose 1 phosphate to uridine tri-phospjate (UTP) which generates UDP-glucose (active form of glucose )
  • Breakdown of pyrophosphosphate to Pi generates energy
58
Q

What is the formation of UDP-glucose

A

Catalyzed by UDP-glucose pyrophosphorylase

59
Q

What is the second step of glycogenesis

A
  • pre-exhisting glycogen polymer serves as primer to which glucose units are added
  • Glycogen synthase (rate limiting enzyme) catalyzes transfers of glucose from UDP-glucose to non reduing end of lcogen chain. forms alpha - 1-4 bond s between glucose molecules
60
Q

how does chain elongation work`

A

via UDP glucose and glycogen using glycogen synthase

61
Q

What is the 3rd step in glycogenesis ?`

A
  • when glycogen chain reaches 11 residues, a fragment of the cain (about 7 residues long) is broken off at an alpha -1,4 link and reattached elsewhere through an alpha -1,6 link by glucosyl (4:6) transferase
  • The new branch point must be at least 4 residues away from a pre-exhisting branch
  • branching increases solublity of glyogen and increases number of terminal non-reducing ends
  • increases rate at which glycogen can be sythesized and degraded

( glycogen (4:6) transferase leads to creation of more non reduced ends )

62
Q

know these images ?

A
63
Q

What is glycogenolysis

A
  • glycogen broken down to release glucose-1-phosphate
  • glycogen remnant remodeled to permit futhur degradation
  • glucose -1-phosphate converted to glucose -6-phosphate
    • Gylcolysis
    • free glucose for release into blood strream
    • pentose phosphate pathway
      • NAPH and ribose derivative
64
Q

WHat are the four key enzymes involved in glycogenolosys

A
  • One to degrade glycogen (Chain shorten)
    • glycogen phosphorylase
  • Two to remodel glycogen remnants
    • phosphoglucomutase
      • converts gluc-1-phosphate to Gluc-6-phosphate
    • transferase
  • One to convert glycogen break down
    • Product suitable for further metabolism
      • alpha1,6-glucosidase

fill out later

65
Q

How dose hcain shortening occur in glycogenolysis?

A
  • Glycogen phosphorylase(GP) = rate limiting enzyme catalyzes the cleavage of glycogen
  • Chain shortening occur at the non reducing end of the polymer (similiar to glycogen synthase) GP adds an orthophosphate and releases a glucose residue as glucose-1-phosphate
  • Uses pyridoxal phosphate (vitamin B6) as a cofactor
  • Phosphorolysis of glucose residues continues till the GP gets within 4 residues of the alpha-1,6 linkage of a branch point
66
Q

What does phosphoglucomutase do in glycogenolysis ?

A

Converts gluc-1-phosphate to gluc-6-phosphate

A phosphoryl group is transferred from the enzyme to the substrate, and a different phosphoryl group is transferred back to restore the enzyme to its initial state

67
Q

How does branch transfer and release of glucose occur?

A
  • Transferase transfers a block of 3 of the remaining 4 glucose to the non-reducing end of the main chain forming an alpha-1,4 bond
  • debranching enzyme or alpha-1,6 glucosidase cleaves the alpha 1,6 bond of the single remaining glucose residue to trelease the free glucose. Glucose phosphorylated by hexokinase
  • Transferase and alpha 1,6 glucosidase conerted branch glycogen into a linear structure for futhrur action by GP
68
Q

What does alpha 1,6 glucosidase do?

A
69
Q

What is the glucose 6 phosphatease step?

A
  • Converts G6P to glucose which can be released in blood stream ebcause G6P cannot get out of the cell
  • Only the liver has glucose 6- phosphatase
  • muscle cells do not have glucose 6-phosphatase so gluc-6-phosphate stays
70
Q

What is lysosomal Glycogenolysis?

A
71
Q

What is the overview for glycogen

A
72
Q

WHat is an overview of glycogen metabolism?

A
73
Q

How is glycogen synthesis regulated

A

gluc-6 -phosphate favors glycogen synthesis

74
Q

How is glycogen breakdown regulated?

A

active “a” form (R relaxed state “phosporylated ) in liver = glycogen phosphorylase A

INactive “b” form ( tense state) in muscle = glycogen phosphorylase B

75
Q

How is glycogen phosphorylase regulated

A
  • low blood sugar
    • ephineprine
    • glucoagone
    • glycogen break down promoted
    • glycogen synthesis inhibited
  • High blood suga
    • insulin
      • glycogen synthesis promoted
      • breakdown inhibited
76
Q

WHat are the different interconversion between the various forms of GP?

A
77
Q

How does liver glycogen phosphorylase compare to muscle GP?

A
78
Q

how does allosteric regulation occur in liver GP?

A
79
Q

How does allosteric regulation occur in muscle GP?

A
80
Q

How does the regulation of the glycogen metabolism occur?

A
81
Q
A
82
Q

What is the mechanism for insulin regulation?

A
83
Q

What are the characteristics for type 2 diabetes?

A
84
Q

What is the hormonal control of GP?

A
85
Q

What is the role of phosphorylation ?

A
86
Q

How does the activation of phosphorylase kinase occur and what does it result in

A
87
Q
A
88
Q

how does glucagon regulation occur?

A
89
Q

How does epinephrine regulation occur

A
90
Q

What is the off switch glycogen metabolism

A
91
Q

How does the fate of glu 1/ gluc 6 - p compare from lver to muscle

A
92
Q
A

know both of these diagrams (no comparsons just understand them )

93
Q
A
94
Q

What is GSD 0?

A
95
Q

What is GSD IV (Andersen Diease) ?

A
96
Q

What is GSD III or Cori diease ?

A
97
Q

What is GSD V or MCardle Diease

A
98
Q

What is GSD VI or Hers disease?

A
99
Q

How is Enzyme replacement therapy used to treat pompe disease (GSD III)?

A

Biochemistry KCUMB (6 decks)

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