Glycolysis and ETC Flashcards

1
Q

Glucose Transporters:
(Tissue, Km, Features)

GLUT1

A

Tissue: Brain, RBCs, placenta, fetal tissue

Km: low

Efficient binding allows constant uptake of glucose

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2
Q

Glucose Transporters:
(Tissue, Km, Features)

GLUT2

A

Tissue: Liver, kidney, intestines, pancreatic B-cells

Km: high

glucose export by the liver & glucose sensor for pancreatic B cells

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3
Q

Glucose Transporters:
(Tissue, Km, Features)

GLUT3

A

Tissue: Brain

Km: Low

Very efficient binding gives preferential uptake during hypoglycemia

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4
Q

Glucose Transporters:
(Tissue, Km, Features)

GLUT4

A

Tissue: Muscle, adipose

Km: Medium

INSULIN SIGNALING recruits GLUT4 to cell surface during fed state to increase uptake

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5
Q

Fed State: Absorptive Phase in Liver

I/G ratio, time since meal, energy producing, CHO storage and lipid storage pathways

A

High I/G

0-4 hours after mixed meal

Energy producing (First Priority):

  • Glycolysis
  • TCA cycle
  • ETC & ATP Synthase
CHO Storage (Second Priority):
-Liver glycogenesis
Lipid Storage (third priority):
-lipogenesis (FA synth + TAG synth)
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6
Q

Glycolysis Activity in Fed & Fasting States for:

Liver, Muscle, Adipose, Brain/RBC

A

FED: All tissues oxidize glucose

FASTING: only brain and RBCs since they can’t oxidize FFAs

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7
Q

A. Where does glycolysis occur?

B. Where does ATP, GTP and reduced e- carrier production occur?

C. Where does most NADH production occur?

A

A. Cytoplasm

B. Cytoplasm and mitochondrial matrix

C. Mitochondria

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8
Q

Net energy production of Glycolysis:

A

2 ATP, 2 NADH (shuttle e- to ETC)

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9
Q

Glycolysis:

  • Starting substrate & End Product
  • Location
  • Enzymes
  • Purpose
A

Glucose–>Pyruvate

Location: Cytoplasm

Enzymes:
-Glucokinase (liver)/Hexokinase (muscle, fat)

  • PFK-1 (Rate limiting)
  • Pyruvate Kinase

Purpose:

  • NADH + ATP production
  • Generation of intermediates for other pathways (i.e. pyruvate, ACoA, lactate)
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10
Q

Glucokinase:

  • Step active
  • Function
  • Km
  • Vmax
  • Regulation
A

Step active:
-Glucose–> G6P (liver)

Function:

  • Sugar trap for hepatocyte
  • Phosphorylates glucose to G6P (neg charge) so it cannot cross membrane
  • Removes large amount of glucose from portal blood

Km/Vmax:
-High Km and Vmax

Regulation:
-synthesis increased by insulin

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11
Q

Hexokinase:

  • Step active
  • Function
  • Km
  • Vmax
  • Regulation
A

Step active:
-Glucose–> G6P (other tissue)

Function:

  • Sugar trap
  • Phosphorylates glucose to G6P (neg charge) so it cannot cross membrane
  • works even during fasting state

Km/Vmax:
-Low Km and Vmax (high affinity)

Regulation:

  • Synthesis increased by insulin
  • Inhibited by G6P
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12
Q

PFK-1

  • Step active
  • Function
  • Regulation
A

Step Active:
F6P–>F1,6BP

Function:

  • activated by F6P metabolite F2,6BP
  • F2,6BP binds to PFK-1, increasing activity
  • Fasting state, F2,6BP levels decrease via dephosphorylation, PFK-1 activity decreased

Regulation:

  • Activators: F2,6BP, AMP
  • Inhibitors: ATP, citrate
  • Synthesis increased by high I/G

NOT REGULATED DIRECTLY BY PHOSPHORYLATION

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13
Q

Pyruvate Kinase (PK)

  • Step active
  • Regulation
A

Step Active: FED STATE
-PEP to Pyruvate

Regulation:
1. Activated by F1,6BP via “feed forward”

  1. Rule of Thumb phosphorylation
    - High I/G: Dephosphorylated and ACTIVE
    - Low I/G: phosphorylated by PKA and INACTIVE
  2. [PK]
    - Insulin increases PK synthesis
    - Glucagon decreases PK synthesis
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14
Q

Oxidation of Pyruvate:

  • Location
  • Starting substrate & End Product
  • Enzymes
  • Purpose
A

Pyruvate–> Acetyl CoA

Location: cytoplasm, can be imported to mitochondria via transporter

Enzyme: PDHC

Purpose: generate ACoA for TCA cycle or FA synthesis

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15
Q

PDHC:

  • Features
  • Function
  • Coenzymes and precursors
  • Regulation
A

Pyruvate –> ACoA

Features:
-mitochondrial protein complex, 3 enzymes 5 coenzymes

Coenzymes & Precursors:

  • TPP & Thiamine (B1)
  • FAD & Riboflavin (B2)
  • CoA and Pantothenate (B5)
  • NAD+ & Niacin (B3)
  • Lipoic Acid

Function:
-Turns Pyruvate to ACoA, creates NADH

Regulation:

  • Inhibited by high [ACoA and NADH]
  • Fasting state, accumulation of NADH and ACoA from beta oxidation
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16
Q

TCA Cycle:

  • Pathway
  • Enzymes
  • Purposes
A

Pathway: Mitochondria
-ACoA–> CO2, GTP, NADH, FADH2

Enzymes:

  • Citrate Synthase
  • Isocitrate Dehydrogenase
  • alpha ketoglutarate dehydrogenase

Purpose: Highly active in fed state, slows greatly in fasting

  1. Generate 3NADH and 1 FADH2
  2. Generate 1 GTP (bond energy)
  3. Generate citrate for FA synth
17
Q

Citrate Synthase:

A

-ACoA–>Citrate

Regulation:

  • Inhibited by citrate
  • Can use OAA and ACoA as substrate
18
Q

Isocitrate dehydrogenase

A

Rate limiting enzyme of TCA cycle

Function: Isocitrate–>alpha ketoglutarate, CO2

Regulation

  • Inhibited by NADH + ATP
  • Activated by ADP
19
Q

alpha ketoglutarate dehydrogenase

A

multienzyme complex

Requires same coenzymes as PDHC:

Coenzymes & Precursors:

  • TPP & Thiamine (B1)
  • FAD & Riboflavin (B2)
  • CoA and Pantothenate (B5)
  • NAD+ & Niacin (B3)
  • Lipoic Acid
20
Q

TPP and Thiamine importance

A

deficiency affects TCA cycle.

-Aerobic tissue like brain and cardiac muscle will fail first with deficiency

21
Q

Arsenic poisoning

A

Arsenic binds to thiol group of lipoic acid, preventing its function as a coenzyme.

22
Q

Functions of metabolism of Pyruvate to OAA

A
  1. It supplies additional substrates to
    increases the speed of the TCA cycle (a
    phenomenon called TCA Cycle priming)
  2. It allows more synthesis of citrate for
    oxidation and for fatty acid synthesis.
23
Q

ETC:

NADH donates e- to where?

A

complex I–>III,IV

24
Q

ETC:

FADH2 donates e- to where?

A

complex II–>III,IV

25
Q

Uncouplers

A
-class of integral membrane proteins in mitochondria that create “proton leak” at the inner
membrane, allowing H+ to flow down its concentration gradient 
  • electron transport chain increases in speed. The increased rate of the ETC, with no ATP
    synthesis, causes the energy to be released as heat
26
Q

PDHC: TPP Coenzyme

A

B1

27
Q

PDHC: FAD Coenzyme

A

B2

28
Q

PDHC: CoA Coenzyme

A

B5

29
Q

PDHC: NAD+ Coenzyme

A

B3