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Carb Metabolism Flashcards

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1
Q

what Zs are secreted in the mouth?

A

salivary amylase and lingual lipase

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2
Q

What are the 4 players of chem digestions in the stomach?

A
  1. Gastrin (hormone)
  2. Gastric Lipase
  3. HCL
  4. Pepsinogen–> activated to PEPSIN (Zs)
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3
Q

In what organ (s) does peristalsis take place?

A

Stomach

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4
Q

in what organ(s) does segmentation take place?

A

SI and LI

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5
Q

In what organ(s) does propulsion take place?

A

Stomach, SI and LI

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6
Q

what are the three types of mec digestion?

A

Peristalsis
segmentation
propulsion

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7
Q

what Zs are secreted by the pancreas, needed for digestion of all macromolecules?

A
  1. Trypsinogen
  2. Chymotrypsinogen
  3. carboxypetidase A and B
  4. Pancreatic lipases 5. pancreatic amylases
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8
Q

where does protein digestion begin?

A

stomach with pepsin and HCL

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9
Q

in what organs in there absorbtion?

A
  • Stomach (alc and aspirin–> lipophilic)
  • SI : AAs, S-C/M-C lipids, glc, fruct, water minerals, vit
  • LI: Water, ions, minerals, vit, oranic molecules
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10
Q

where are water, minerals and vit absorbed?

A

in SI and LI

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11
Q

What digestion happens in the LI?

A

NO chem, just mec
bacterial fermentation
absorption

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12
Q

What are the 4 fates of glucose in metabolism?

A

SSOgOp

  1. Synthesis of structural polym. ( cell wall polys. and ECM)
  2. Storage ( glycogen, starch, sucrose)
  3. Oxidation through glycolysis to yield pyruvate
  4. Ox through PPP to yield R5-P
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13
Q

What are the 2 uses of glucose? describe them

A 
FUEL (E mol):
1. Source of E
2. Efficiently stored (glyc.)
3. only source of e for many tissues (brain and muscle)
PRECURSOR for other mol:
1. AA
2. FA synth (for storage)
3. NA : DNA and RNA nucleotide synt
4. cofacttors
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14
Q

What are the 4 glucose metabolic pathways?

A
  • Gluconeogenesis: synt of glc form non-carb sources
  • glycolysis: oxid. of glc to 2 pyr
  • glycogenesis: synth of glyc from glc
  • glycogenolysis: degradation of glyc into glc monomers
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15
Q

In what steps of glycolysis is ATP consumed (priming rxns) ?

A

Steps 1 and 3

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16
Q

What are the steps in the prep phase of glycolysis (including Zs) ?

A 
Steps 1-5
1. HEXOKINASE 
G1P -->G6P
ATP hydrolysis
2. PHOSPHOHEXO ISOMERASE 
 F6P
3. PFK-1
-->1,6 FbP
ATP hydrolysis
4. ALDOLASE
 GAP + DHAP
5. TRIOSEPHOSPHATE ISOMERASE
DHAP  GAP
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17
Q

what are the steps in the payoff phase of glycolysis (including Zs)?

A 
steps 6-10
6. GAPDH
GAP  1,3 bPG
2 NADH
7. PG KINASE
3-PG
2 ATP
8. PG MUTASE
 2-PG
9. ENOLASE
 PEP
10. PYRUVATE KINASE
-->PYR 
2 ATP
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18
Q

In what steps of glyc is ATP produced?

A

steps 7 (2 ATP) and 10 (2 ATP)

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19
Q

What step in glycolysis produces NADH?

A

step 6:

GAP 1,3 bPG

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20
Q

what is tautomerization?

A

intercoversion between 2 isomers (pyruvate)

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21
Q

Why is it important to have a symmetric molecule? In what steps of glyc. does this occur?

A

steps 2 and 3–>

  1. isomerization to a ketose sugar creates a symmetrical ring
  2. addition of phosphate to symmetrical ring (one one either side)
    * important because aldolase will cleave the molecule into 2 3C high E phosphate sugars.
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22
Q

what steps in glyc. are irreversible?

A

steps 1-3-10
1. 1st ATP consumption step (priming rxn)
3. step of no return (commitment to glyc.)
2nd ATP consummed
10. last step (final synth of ATP)

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23
Q

What are the advantages of the 1st step of glycolysis?

A

PHOSPHORYLATION
- prevents the glucose for diffusing back out thoguhthe cyt mem.
- decreases the amount of intracellular unphosphorylated glc which increases glucose uptake by creating a [ ] grandient.
IRREVIRSIBLE:
traps glc in glyc

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24
Q

what is the net yield of glycolysis?

A

2 ATP

2 NADH

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25
what are the catabolic fates of pyruvate?
anerobic: 1. yeast alcohol fermentation 2 pyr--> 2 ethanol + 2 CO2 2. fermentation to lactate (producing NAD) aerobic: 3. oxidation to acetyl-coa--> complete oxidation 2 CO2 and H2O
26
what allows for the regeneration of NAD+ in glycolysis?
the anaerobic conversion of pyr---> lactate (using the NADH produced in glycolysis)
27
Why does NAD+ need to be regenerated in glyc?
so glycolysis can continue, without NADH accumulation
28
what tends happens to lactate in muscle cells
CORI CYCLE
29
what tends happens to lactate in muscle cells
CORI CYCLE: | lactate can be converted back to glucose
30
what can be converted to glucose 1-P to enter glyc?
- dietary or endogenous glycogen - D-glc - Galactose--> UDP-gal--> UDP-glc
31
What can be converted to gluc 6-P (2nd int) to enter glyc?
-trehalose--> D-glc
32
what can be converte d to fruc 6P to enter glyc?
- D-fruct | - Mannose--> mannose-6P
33
what can be converted to GAP to enter glycolysis?
-D-frct-->fructose-1P--> DHAP+ GAP | DHAP-->GAP
34
What are the 3 Zs unique to gluconeogenesis and what steps of glycolysis do they correspond to ?
``` steps 1, 3, 10 --> irreversible steps 10. pyruvate carboxylase PEP carboxykinase 3. 1,6Fbphosphatase 1. G6P-phosphatase ```
35
what can undergoe gluconeo. in animals?
- lactate--> pyr--> oxalo. - glucogenic AAs--> TCA int.--> oxaloacetate - glycerol--> G6P
36
What can undergoe gluconeo. in plants?
- fixed CO2--> 3 P-G - glucogenic AAs -
37
What can undergoe gluconeo. in plants?
- fixed CO2--> 3 P-G - glucogenic AAs - glycerol--> G6P
38
what is the E requirement for gluconeogenesis?
8 ATP | 2 NADH
39
What tissues require solely glucose as E source?
neurons, muscles, RBCS, testes, renal, medulla
40
what is the most common fate of G6P? what is its alternate fate and in what cells/conditions does this most commonly happen?
glycolysis= most common PPP= alternative fate - ox stress ( in RBCs) - reductive biosynthesis : FA (liver, kidney, mammary gland) , sterol (gonads, adrenals, liver) - proliferating cells: need for high gene espression= synth of NA and CoZs
41
What is the most common pathway used by cells to generate NADPH?
PPP
42
what are the 2 phases of PPP and their roles? And how are they connected?
Ox: - prevention of ox damage (generation of NADPH) - R5P synth - redutive biosynthesis Non-Ox: R5P recycling--> G6P may reenter the cycle
43
What intermediates of glycolysis are shared with the PPP? what is their role in PPP?
G6P (Ox Phase): - prevention of ox damage - R5P synth - generation of NADPH GAP (N-O phase): - R5P recycling--> G6P may reenter the cycle
44
what enzyme and fn is reg in PPP?
G6P DH oxidzes G6P and produces NADPH. activated or inhibited depending on context. (NADPH availability)
45
What is a - regulator of PPP?
NADPH
46
What are the Zs and their fns of PPP Ox phase?
1. G6P DH--> NADPH synth 2. Glutathione reductase--> reduction of glutathione (--> 2 GSH) 3. Glutathione peroxidase (reduction of peroxide to water)
47
What are the 2 main Zs involved in PPP's N-Ox phase? and what is their implication in cancer?
Transketolase and transaldolase. They are overexpressed in cancer cells= highly proliferating cells/ hypoxic conditions--> need a lot of glucose
48
what proteins are involved in regulation of glycolysis under hypoxic conditions and what is the ultimate result?
HIF-1 (alpha and beta) CBP (cAMP RE binding prot.)--> bind to HRE dowstream target gene= induce expression--> promotes uptake of glucose and functioning of glycolisis
49
What happens under normoxic conditions (regulation of glycolysis)?
PHD (Prolyl Hydroxyalse is active)--> pre-hydroxylation of HIF-alpha--> targetted for degradation= ubiquitinated--> does NOT INDUCE gene expression.
50
What genes do HIF and CBP induce?
GlUT 1/3 Glycolysis Zs lactate DH
51
What Zs are regulated in glycolysis?
Zs of the irreversible steps (1/3/10): 1. Hexokinase 3. PFK-1 10. Pyr Kinase
52
What Zs are regulated in gluconeo.?
irr. steps glyc. 10. pyr. carboxylase PEP carboxykinase 3. F1,6bphosphatase-1 1. G6-Phosphatase
53
Explain how PFK-1 is regulated? what activates and what inhibits?
This Z of glycolysis is regulated allosterically: - indicators of high E (ATP and citrate) inhibit - indicators of low E (AMP/ADP) acitivate
54
Where do you find PFK-2/FBPase-2 Z and how is it regulated to promote glycolysis?
this bifunctional Z is found in the liver. When [F2,6bP] is high, its PFK-2 part is activated by DEPHOSPHORYLATION by the Z PHOSPHOPROTEIN PHOSPHATASE (activated through insulin singalling pathway by deP. )--> glycolysis is promoted
55
Where do you find PFK-2/FBPase-2 Z and how is it regulated to promote glycolysis?
this bifunctional Z is found in the liver. When [F2,6bP] is high, its PFK-2 part is activated by DEPHOSPHORYLATION by the Z PHOSPHOPROTEIN PHOSPHATASE (activated through insulin signalling pathway by deP. )--> glycolysis is promoted
56
What hexokinase isozymes are found in liver vs. muscle?
Liver: hex IV muscle: Hex. I and II
57
How is hex. IV regulated? what activates what inhibits?
Already, this hexokinase, being in the liver, has a low affinity for glucose. nevertheless, - it is activated by glucose ( the substarte) - it is inhibited by F6P (dowstream product) --> -ve feedback - it is inhibited by glucosekinase regulatory protein, which binds to the Z and brings it into the nucleus, where it cannot perform its function.
58
How is hex. IV regulated? what activates what inhibits?
Already, this hexokinase, being in the liver, has a low affinity for glucose. nevertheless, - it is activated by glucose ( the substarte) - it is inhibited by F6P (dowstream product) --> -ve feedback - it is inhibited by glucosekinase regulatory protein, which binds to the Z and brings it into the nucleus, where it cannot perform its function. (NOT REGULATED BY G6P)
59
How is hexokinase II and I regulated? what activates? what inhibits?
These, isoforms, being in the muscle, have a high affinity for glucose. REGULATED BY G6P (direct product): allosteric inhibition
60
Where do you find PFK-2/FBPase-2 Z and how is it regulated to promote gluconeogenesis?
in liver. low [F26bP] promotes gluconeogenesis by PHOSPHORYLATION ( by the cAMP-dep. binding protein activated by glucagon signalling (GPCR)) of the Z, activating the FBPase part.
61
what is the role of insulin in the liver? does it promote gluconeogenesis or glycolysis?
Insulin release is triggered by higher blood glucose concentration and thus promotes utilization of glc through glycolysis to yield E. In the liver, insulin signals the phosphoprotein phosphatase to dephosphorylate the PFK-2/FBpase-2 Z.
62
what is the role of glucagon in the liver? does it promote gluconeogenesis or glycolysis?
Glucagon is released in conditions of low blood glucose and therefore promotes to synth of glucose through gluconeogenetic pathway. In the liver, it signals c-AMP dependent prot kinase to phosphorylate PFK-2/FBpase-2 Z.
63
Where is F2,6bP found and what is its role?
it is found in the liver and its role is to regulate PFK-2/FBpase-2 Z: - low conc: stimulates gluconeogenesis - high concentration: stimulates glycolysis
64
What cell condition promotes hexokinase IV?
activated by indicators of low E.
65
What cell condition promotes G6--phosphatase?
activated by indicators of high E.
66
What genes are expressed by insulin? What are their roles?
``` genes coding for glycolytic Zs and Zs promoting NADPH production : Hexokinase isomers II and IV Pyr Kinase PFK-1 PFK-2/FBpase-2 Z ``` G6P-DH Malic Z 6- phosphogluconate DH
67
What genes are suppressed (decreased expression) by insulin? what are their roles?
genes coding for gluconeogenetic Zs: PEP carboxykinase G6Phosphatase
68
What is insulin's role in activating FOXO1?
insulin pathway leads to the Ph. of FOXO-1 targetting it for degradation and thus, avoids, its activity of suppressing genes promoting glyc.
69
How does Acetyl-CoA regulate glucose metabolism in the liver?
high [ ] --> indicator of potential to yeild high E through TCA or B-ox, therefore, inhibits pyruvate kinase and activates pyruvate carboxylase.
70
How is pyr kinase regulated in the liver?
reg by dephosphorylation by phosphoprot. phosphatase. | high [cAMP] stimulates GLUCAGON signalling--> PKA--> phosphorylates--> deactivates
71
how is pyr kinase regulated in the muscles?
like with hexokinase 1 and 2, it is regulated allosterically: - indicators of high E inhibit - Alanine ( indicator of sufficient pyruvate) inhibits - previous substrate (F16bP) activates
72
How does Xylulose 5p (from where is it generated?) help regulate glycolysis?
Xylulose5P, generated from G6P in PPP, stimulates deph. of TF. Once deph, the active TF can enter the nucleus, to bind and promote gene expression activating glycolysis and fa synth,
73
how is ChREB involved in activation of glycolysis?
carb Response element binding proting is a TF, that, once activated by deph., promotes gene expression of glycolytic Zs. genes
74
What active form of FOXO1 promotes glc synthesis?
FOXO must be deph. in order to enter nucleus and act as a TF to stimulate gene expression of gluconeogenesis genes,
75
What is chREB and how is it activated?
cab response element binding protein, activated by deph.
76
What are the different methods of transcriptional regulation of Zs involved in glucose metabolism?
1. insulin pathway: - promoting glycolysis and NADPH production - unfavoring gluconeo. 2. through deph,: - ChREB - FOXO (insulin pathway deactivates it) **complex regulation--> combination of TFs
77
what pathways of glucose metabolism happen predominantly in the liver?
glycogenesis, gluconeogenesis
78
what is UDP-glucose?
sugar nucleotide
79
Where does glycogen synthesis predominantly take place? by which Zs?
in liver by: 1. UDP-glucose pyrosynthase 2. glycogenin 3. glycogen synthase 4. branching Z
80
Where does glycogen breakdown predominantly take place? by which Zs?
``` in liver. Zs: 1. GLYCOGEN PHOSPHORYLASE 2. DEBRANCHING Z - TRANDFERASE ACTIVITY -GLUCOSIDASE ACTIVITY 3. PHOSPHOCLUGOMUTASE 4. G6PHOSPHATASE ```
81
What are the 5 steps of glycogenesis?
1. UDP-glucose formation Glucose phosphate ( 1 P) + UTP--> 2 Pi + UDP-glucose ( 2 P) 2. UDP-glucose attachment to hydroxylated tyrosine residue of Glycogenin Z (active site). Intitiation of a short chain (minimum 4 units) by sequences of removal of UDP and addition of new UDP-glucose at C4 (glycosyltrasnferase activity), and, removal of second UDP (chain extending activity). 3. elongation: addition of UDP-glucose a the non-reducing end of the initial chain( glycogen synthase) 4. branching z: cleaving the C4-C5 glyc, bond after 4 sequential unit from the glycogen core and attaching it to the 5th unit of the chain. (alpha 1-6 bond) C1 chain- C6 branch. 5. elongation of the branch: by glycogen synthase
82
explain the 2 activities of glycogenin?
1. glycosyl transferase: removal of first UDP and addition of a new UDP-glc at C4 of existing glucose. 2. chain extending: formation of C1-C4 bond and removal of second UDP--> forming a nonreducing end
83
What are the benefits of glycogen being highly branched?
Because of creation of more non-reducing ends/ more potential to H-bond: - water soluble - more points for cleaving--> quick source of energy
84
What are the 5 steps of glycogenolysis?
1. Cleaving off glucose units by phosphorylation, freeing G1P's, until the minimum of 4 unit chain is reached 2. Debranching: transferase - Cleave off 3 units off the branch and attach them to the glycogen chain (C1-C4) 3. Debranching: glucosidase - cleave the alpha-1-6 glycosidic bond between the 1 unit of the branch left and the first unit of the glycogen chain--> free glucose 4. phosphoglucomutase: G1P--> G6P 5. G6phosphatase: G6P--> Glucose
85
What are the 2 activities of the glycogen debranching Z? explain
1. transferase: cutting 3 units from branch and transfering them to the nonreducing end of the glycogen chain 2. glucosidase: cleaving the alpha 1-6 glycosidic bond
86
what Zs of glycogen synthesis and breakdown are activated by DEPHOSPH.?
glycogen synthase
87
what Zs of glycogen synthesis and breakdown are activated by PHOSPH.?
glycogen phosphorylase
88
what are the points of regulation (Zs) in glycogenesis?
- glycogen synthase -UDP-glucose pyrophosphorylase - phosphoglucomutase G6P-->G1P
89
what are the points of regulation (Zs) in glycogenolysis?
- glycogen phosphorylase - phosphoglucomutase G1P-->G6P--> glycolysis
90
describe regulation of glycogen breakdown in resting vs. contracting muscles
RESTING: dephosphorylation of PHOSPHORYLASE KINASE B= remains inactive and cannot cleave off glc units (glycogen source in mucle is not depleted). CONTRACTING: phosphorylation= activation of PHOSPHORYLASE KINASE B--> Ph. GLYCOGEN PHOSPHORYLASE B--> (active) GLYCOGEN PHOSPHORYLASE A
91
what hormone acts on muscles in glycogenolysis? what is the final outcome?
epinephrine released in conditions of fight or flight, when muscle needs to contract quickly and intensely. final outcome: muscle contraction caused by quick release of energy from glycolysis. Therefore, G1P (from glycogenolysis)--> G6P--> glycolysis
92
what hormone acts on liver cells in glycogenolysis? what is the final outcome?
glucagon released in conditions of low blood glucose: final outcome: increase in blood glucose as G1P--> glucose (enters gluconeogenesis) **glucose is typically sent to other tissues
93
What is glycogen phosphorylase B's fn and how/in what condition is it activated?
it is an Z of glycogenolysis which, when activated, fns by cleaving glc units off glycogen by phosphorylation. It is also activated by phosphorylation--> phosphorylase a.
94
By what signalling pathway is glycogenesis hormonally regualted?
PI3 RTK pathway (insulin mediated= ACTIVATOR)
95
what are the activators of glycogenesis?
- indicators of high E: ATP, (high levels), G6P, INSULIN
96
what are the inhibitors of glycogenesis?
-indicators of low E: GLUCAGON/EPINEPHRINE
97
What is the main Z of glycogenesis and how is it activated?
glycogen synthase is activated when dephosphorylated ( inactivation of GSK3 by PKB)
98
what are the 3 outcomes of glucose metabolism in liver when blood glucose is high?
- increase in glycolysis ( because of high substrate) - increase of glycogen synthesis ( glucose storage) - decrease of glycogen breakdown
99
what are the 3 outcomes of glucose metabolism in liver when blood glucose is low?
- decrease in glycolysis (not much substrate available) - decrease of glycogen synthesis - increase of glycogen breakdown ( to release a source if E)
100
what hormone is released in conditions of high blood gluc? and what is its action on Zs of glycolysis, glycogen break down and synthesis?
INSULIN: - --> activation Zs of glycolysis (Hex II, PFK-1, pyr kinase) - -> deactivation of Z's of glycogenolysis: deP of phosphorylase kinase and glycogen phosphorylase - -> activation of Z's of glycogen synthesis: deP. glycogen synthase
101
what hormone is released in conditions of low blood gluc? and what is its action on Zs of glycolysis, glycogen break down and synthesis?
GLUCAGON: - -> deactivates Zs of glycolysis by phosphorylation: PFK-2 part of bifunctional Z, pyruvate kinase - ->deactivates Zs of glycogen synthesis: Ph. of glycogen synthase - -> activates Zs of glycogen breakdown: Ph. phosphorylase kinase which Ph. phosphorylase Z.
102
What 2 scenarios does high blood glucose stimulate?
1. insulin pathway= affects glucose met. in 3 ways 2. stimulation of transport of glucose in through GLUT 2--> increase intracellular [glc]= increase glycolysis
103
how does active GLUT 2 regulate glucose metabolism?
by transporting more glc from ciruculation= increases amount of intracellular glc--> stimulates glycolysis

Biochem 2 (12 decks)

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