Glycolysis/TCA Flashcards
3 stages of respiration
- Polymers of nutrients broken down
- monomers broken down in pathways to Acetyl CoA tat is fed into TCA cycle. Energy transfered to NADH and FADH2
- Electrons funneled into ETC in mitochondria wall. ADP/O2 consumed and water/ATP created
What cells is glycolysis major source of energy
RBC (no mitochondria), sperm, retina
why do we add phosphates
need to activate glucose before energy can be released
2 phases of glucose
preparatory phase and energy generation (payoff) phase
Prep phase
- Glu –> G3P
- 2 ATP invested to activate glucose to increase free-energy content
Payoff phase
extract energy
Glucose transporters
Glut4 - present in insulin-sensitive tissues (sk muscl and adipose); increases transport after insulin exposure
Glut 2 – in liver; amount of transporter in membrane doesn’t change in response to insulin levels
3 types of reactions in glycolysis
- degrade carbon skeleton to pyruvate, whose fate depends on cell type (mitochondria) and metabolic circumstances (presence of oxygen)
- phosphorylatio of ADP–ATP (substrate level phosphorylation)
- generate NADH and go to ETC if oxygen present or convert back to NAD if no mitochondria/oxygen
importance of first step in glycolysis
- traps glucose in cell
- conserves energy in form of bond
- binding of phosphate on G6P to active site of next enzyme lowers activation energy and increases specificity
PFK1
catalyzes rate limiting enzyme of glycolysis
- allosteric enzyme, sensitive to energy status of cell (ATP/citrate)
PFK2
- bifunctional enzyme
- kinase or phosphatase
- converts between F6P and F2,6 BP
- in liver, kinase active if dephosphorylated and inactive if phosphorylated
- adding P increases free energy of reactants
F2,6BP is the most potent activator of PFK1 even when high ATP
what activates PFK1
AMP, Fructose 1,6 BP
what inhibits PFK1
ATP, citrate
enzyme deficiencies causing hemolytic anemia
1- G6PD deficiency (most common)
2. Pyruvate kinase deficiency (2nd most common)
which tissues convert lactate to pyruvate
heart/liver
why is pyruvate so important
it is a hub for number of pathways depending on metabolic state (fed vs fasted), tissue involved and available substrates
final product of aerobic glycolysis vs anaerobic
Aerobic: pyruvate – enters into TCA
Anaerobic: pyruvate converted to lactate to regeneration NAD+; lactate exported out of cell
pyruvate in fed state
- convert to alanine (aa)
- if lots of carbs – increased Acetyl COA for faty acid synthesis
Pyruvate in Fasting
- pyruvate from lactate converted tooxaloacetate to provide carbon skeleton for gluconeogenesis
Thiamine deficiency
- Wernicke’s encephalopathy
- can’t oxidize pyruvate, which is important for fueling the brain
- characterized by neurological deficiencies–> altered mental status, cranial nerve palsies
- clinically high pyruvate in blood
- mutations in genes for subunits of PDH has similar consequences
- can also present as heart failure
PDH
pyruvate dehydrogenase complex
- important in converting pyruvate to Acetyl CoA
- cluster of 3 enzymes in mitochondria plus 5 coenzymes
- kinase and phosphatase also part of complex
PDH coenzymes
coenzyme A, thiamine pyrophosphate (TPP), prostehtic groups, flavin adenine dinucleotide (FAD), nicotinamide adenine, dinucleotide (NAD), and lipoate
which vitamines are essential for PDH cofactors
thiamine (Vit B1) -TPP
riboflavin (Vit B2)- FAD
niacin -NAD
pantothenate - coenzyme A
PDH regulation
allosterically by feedback inhibition by ATP, acetyl CoA, NADH, fatty acids
What activates PDH
AMP, CoA, NAD+; activated when low energy (low ATP/ADP adn low NADH/NAD+)
liver inhibition of PDH
prevent pyruvate –> Acetyl CoA and ensure it can be redirected for gluconeogenesis
- in this state Acetyl CoA= positive effector for pyruvate carboxylase
PDH in fed state
active in de-phospho state, favored by high insulin and high ADP
- phosphatase in complex dephosphorylates to activate complex. Ca stimulates phosphatase
does insulin usually phosphorylate or dephosphorylate
dephosphorylate
does glucagon usually phosphorylate or dephosphorylate
phosphorylate
PDH in fasting
inactive in phosphorylated state
- PDH kinase in complex inactivates PDH
- this kinase is inhibited by pyruvate and stimulated by ATP
role of TCA cycle
creates GTP, FAD2, NADH, CO2 and converts intermediates from one form to another
