Lecture 40 Flashcards
Energy Metabolism I: Glycolysis
1
Q
role of energy production
A
in muscle cells, ATP required for muscle contraction
pg 1060
2
Q
adenosine triphosphate (ATP)
A
- has 2 high-energy phosphate bonds (β and γ) which can be cleaved by H2O
- this reaction of hydrolysis of ATP to form ADP and a free phosphate can be coupled with unfavorable reactions to drive them forwards
pg 1061
3
Q
energy production: substrates
A
- amino acids, glucose, and fatty acids transported into the cells via proteins
- amino acids used in the cell for synthesis of proteins, but they can also produce energy in extreme conditions; form contractile machinery of muscle cells
- fatty acids use a fatty acid transport protein
pg 1062
4
Q
glucose transporters: GLUT 4
A
- found in adipose tissue, skeletal muscle, heart muscle
- insulin-sensitive transporter -> when insulin is present, the number of GLUT 4 transporters increases
- high affinity system
- GLUT 4 stored in intracellular vesicles until insulin is present
pg 1063
5
Q
glucose transport in muscle cells
A
- when insulin binds insulin receptor, it triggers a downstream signaling pathway which tells the intracellular vesicle storing GLUT 4 to translocate to the plasma membrane
- GLUT 4 embeds in the plasma membrane and allows glucose uptake
- clinical correlation: insulin resistance and T2D
pg 1064
6
Q
energy production: GLUT 4
A
- glucose transported into the cell by GLUT4 when insulin in present (high in absorptive/well-fed state)
- once in cell, glucose activated to glucose-6-phosphate
- G-6-P undergoes glycolysis to form pyruvate, ATP, and NADH
- ATP formed from substrate level phosphorylation (transfer of phosphate from one substance to another)
- NADH is electron carrier
- 2 ATP are formed from 1 glucose
pg 1065
7
Q
glycolysis overview
A
- central metabolic pathway
- consist of 10 steps: 3 irreversible, 7 reversible (regulated by availability of substrate/product
- steps are divided in 2 phases: energy investing (2 ATP lost) and energy harvesting (4 ATP gained)
- net energy yield for 1 glucose is: 2 ATP, 2 NADH
- ATP is needed initially to destabilize glucose-6-phosphate energetically
- 3 irreversible steps: 1 (hexokinase/glucokinase), 3 (phosphofructokinase-2), 10 (pyruvate kinase)
pg 1066
8
Q
nicotinamide adenine dinucleotide (NAD)
A
- NAD+ has an oxidized nicotinamide and NADH has a reduced nicotinamide
- pellagra: a deficiency of niacin -> niacin involved in NAD+ synthesis
pg 1067-1068
9
Q
activation of glucose
A
Hexokinase - 1st Reversible Step
- 3 isoforms in muscle -> hexokinase I, II, III
- found in most tissue including muscle
- inhibited by the end product
- high affinity for glucose (low Km) (how glucose stays in the cell)
- low maximal velocity (Vmax)
- tissue specific regulation - in muscle -> inhibitors: glucose 6-P (product)
- converts D-glucose to glucose-6-phosphate and requires ATP
- analog is glucokinase in liver cells -> glucokinase has a low affinity (high Km) and high Vmax
pg 1070
10
Q
glycolysis: PFK-1 step
A
Phosphofructokinase-1 (PFK-1) - 3rd step
- irreversible step
- rate-limiting and committed step
- most important control point
- in muscle, regulated allosterically by: inhibitors: ATP (high energy), citrate, H+; activators: F-6-P (substrate level), fructose 2,6-bisphosphate (in liver in response to high insulin)
- converts fructose-6-phosphate to fructose 1,6-bisphosphate and needs ATP to do so
pg 1072
11
Q
glycolysis: pyruvate kinase
A
- last step of glycolysis
- irreversible step
- tissue specific isoforms: M1 (in skeltal muscle), M2 (in kidney, adipose tissue, lungs), L (in liver, regulated by glucagon), R (in RBCs) -> allows for more specific and precise regulation
- regulated step (tissue-dependent)
- M-type PK regulation is allosteric (NOT regulated by glucagon): inhibitors: ATP (high energy), acetyl-CoA, Ala; activators: AMP (low energy), F-1,6-bisP (feedforward -> upstream intermediate)
- converts 2 molecules of phosphoenol-pyruvate to 2 molecules of pyruvate and releases 2 ATP in the process
pg 1074
12
Q
summary of glycolysis regulation
A
- short-term regulation: allosteric, covalent modifications (phosphorylation/dephosphorylation)
- long-term regulation (in the liver): protein expression
pg 1075
13
Q
energy production: pyruvate
A
- pyruvate enters the mitochondria where it is converted to acetyl CoA
- acetyl CoA goes into the TCA cycle to release NADH and FADH2 (electron carriers)
- NADH and FADH2 go to the electron transport chain (ETC)
- after the ETC, ADP + Pi and O2 are used for oxidative phosphorylation and the release of ATP
- O2 is the final electron acceptor (captures the electron to allow production of ATP)
pg 1076
14
Q
fate of pyruvate: aerobic glycolysis
A
- glycolysis itself does not need oxygen, but its subsequent steps do
- in cells with mitochondria and sufficient oxgen available:
- pyruvate convered into acetyl CoA in the mitochondrial matrix
- acetyl CoA will undergo further breakdown in the TCA cycle
- NAD+ is regenerated through the electron transport chain
- in order for glycolysis to proceed, NAD+ has to be regenerated
- net energy yield: 36-38 ATP
pg 1077
15
Q
NADH transport into mitochondria
A
- NADH is a large molecule so it donates electrons to smaller molecules that can pass through the membrane
- these molecules donate the electrons back to NAD+ or FAD in the mitochondria
- uses 2 shuttles: the glycerol-3-phosphate shuttle (yields 1.5 ATP) OR the malate-aspartate shuttle (yields 2.5 ATP)
pg 1078-1079
