Bioenergetics, OxPhos, metabolism overview - NYIT Flashcards
Cellular respiration
Harnessing ATP out of oxygen and energy serviced from oxidized fuels
Reducing equivalents
FAD2H - 1.5 ATP - complex II
NADH - 2.5 ATP - complex 1
These feed into the ETC to build up a proton gradient for feeding through ATP synthase.
Produced inside mitochondria.
NADH produced outside mitochondria is delivered by glycerol phosphate shuttle and malate - aspartate shuttle (as oxaloacetate)
ETC
Complex I - 4 protons: NADH dehydrogenase. Prosthetic group: FMN (flavin mononucleotide)
Complex II - no protons pumps - coenzyme Q and succinate dehydrogenase. Prosthetic group: FAD
Electrons from both I and II transfer from their prosthetic groups to Q
Ubiquinone - electron carrier two e- onto III
Complex III - 4 protons, transfers e- to cyto b and c1
Cytochrome C - electron carrier, heme proteins. A3 binds e-. One electron (Fe3+ + e-) -> (Fe2+)
Complex IV - cytochrome oxidase - 2 protons, transfers e- to O2, spits out water
Complex V - ATP synthase (F type ATPase) base is Fo and a proton channel, F1 is the head (NC bound to Fo) hexemer - inhibited by binding of oligomycin to the proton channel
4 protons for 1 ATP
ETC Inhibitor
causes rate of respiration to decrease, reduction of proton gradient and ATP synthesis and ATP concentration
ETC uncoupler
these collapse the proton gradient across the membrane by making the IMM leaky to protons
Uncouplers function has proton carriers:
proton gradient decreases
rate of respiration increases
ATP synthesis and ATP concentration decreases
Thermogenesis
Done in brown adipose tissue
Uncoupled atp-synthase from producing ATP to producing heat by formation of channel called endogenous uncoupler (in response to thermogenenin)
Structure and function of mitochondria
outer mitochondrial membrane
Inner mitochondrial membrane - where ETC and ATP Synthase can be found. Proton gradient forms on this membrane
Matrix - where the protons are pumped out of
ATP-ADP exchange
Shuttle for removing newly made ATP in exchange for ADP from the cytosol
Final step of OxPhos
Atractyloside - competitive inhibitor of the exchange, bongkrekic acid is a uncompetitive inhibitor of it.
What is Valinomycin effect on the ETC?
ETC uncoupler
It is an ionosphere antibiotic
Disrupts the proton gradient by causes the transport of K+
Cyanide poisoning and detoxification
ETC inhibitor at cytochrome oxidase by binding to it
Treated with thiosulfate (converts cyanide to thiocyanide) and nitrite (converts hemoglobin to methemoglobin which releases cyanide by binding it)
DNP - 2,4, dinitrophenol
Uncoupler of ETC
Antiseptic, collapses ATP gradient? Or pH?
How does Roteenone and Amytal effect the ETC?
ETC inhibitors
ROtenone - common insecticide
Amytal - depresses the CNS, typically used as a sedative or anticonvulsant
Complex III inhibitor
Antimycin A - inhibits electron transfer at complex III
An antibiotic substance produced by streptomyces
Approximately how much energy is harnesses from fats, carbohydrates and protein?
Fats - 9Kcal/gram
Sugars/Proteins - 4Kcal/gram
Once burned it stays, so whatever isn’t utilized for metabolic energy is stored in adipose
What molecule can be considered a common point among most, if not all, metabolic pathways?
Acetyl CoA
from pyruvate out of glycolysis through pyruvate dehydrogenase
From fatty acids (citrate, triaclyglycerol) and alpha-kept-acids (amino acids)
General glycolysis
Glucose goes in and 2 pyruvate come out, utilizes NAD+ and (2) ATP
When anerobic - produces lactate (an effort for replenishment of NAD+)
When aerobic -> converted to Acetyl-CoA and feeds into TCA
What is lactic acidosis? Why does it happen? What are the physiological responses?
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Describe amino acid catabolism, what does it produce?
Amino acid from proteins get broken into pyruvate, TCA cycle intermediates or Acetyl-CoA
Pyruvate -> Glucose
Glucogenic AA are an important source of glucose during gluconeogenesis (times of low sugar)
Ketogenic amino acids can only produce Acetyl-CoA, then further converted to ketone bodies - > alternate energy source (acid ketosis)
Ammmonia is produces during breakdown of ALL amino acids. Needs to be converted to Urea by urea cycle
Fatty acid breakdown
Beta oxidation gives acetyl coa
When starvation or diabetes energy from gluconeogenesis from amino acids of TCA amino acids
(Depletion of TCA intermediates can stall the cycle, which is the major pathway in fat breakdown)
Ketosis and ketoacidosis: causes, source, site of utilization, associated clinical correlates?
Ketosis - normal amts of ketone bodies from fat metabolism
Ketoacidosis - seen in decrease availability (starvation) or utilization (diabetes) of glucose, also from heavy alcohol consumption
Produced from liver, picked up by muscle and converted to Acetyl-CoA
How is energy stored long term in the body?
Glycogen -> Glucose-6-phosphate
Liver breaks down glycogen and releases it to the blood, also site of gluconeogensis.
Muscle breaks down glycogen but it cannot leave.
Triacylglyceride
Pentode Phosphate Pathway
Generation of NADPH
Production of ribose 5-phosphate
Insulin
Produces by beta cells of the pancreas
Most active after eating, stimulate cellular uptake of glucose
Stimulates glycogenesis and protein synthesis, lipid synthesis
Glucagon and epinephrine
Produced by pancreatic alpha cells
Mobilizes - most active during fasting
Increases glycogenolysis and gluconeogenesis
Stimulates lipolysis
Acts to raise blood sugar levels
Corticosteroids and Thyroid hormones
Long acting hormones
Acts of nuclear receptors
Cortisol acts like epinephrine but chronically
Thyroid hormone is essential for growth and stimulates the basal metabolic rate and thermogenesis (thermogenin)
FED State
High insulin
Low glycogen
Insulin/glycogen ration oils HIGH
Glucose being stored as glycogen in lever and muscle, taken up by brain and kidney as fuel
Amino acids are taken into the liver for protein synthesis
Fatty acids - stored as fat
FAST state
Low insulin
High glucagon
Insulin:glucagon ratio is LOW
Liver breaks down glycogen and releases into blood, muscle breaks down glycogen and uses it
Gluconeogenesis in liver from amino acids
Triacylglycerides released into blood converted to acetyl coa or utilized in liver, or ketone bodies released into blood
Starvation State
low insulin
High glucagon
Glycogen is depleted
Fatty acids from fat are released into blood
Major metabolism in the Brain
active and metabolically expensive (~20% of O2 at rest)
Free glucose
Uses ketone bodies during periods of starvation only
No glycogen
Major metabolism in muscle
Can use glucose, fatty acids, ketone bodies and BCAAs (Leu, Ile, Val)
Some glycogen storage
Working out can lead to lactic acidosis -> excess lactate is transferred by blood to the liver where it is converted to glucose
Metabolism in adipose tissue
Lipolysis while fasting
Lipogenesis when fed
Metabolism in the Liver
Nutrient absorption through hepatic portal vein
All metabolic pathways involve the liver
Fasting: glycogenolysis, gluconeogenesis, ketogenesis
Fed: glycogenesis and lipogenesis
Where do you find beta-oxidation, ketogenesis, Oxidative phosphorylation, gluconeogenesis, urea cycle, glycolysis and fatty acid synthesis within a cell?
Beta-oxidation - mitochondria
Ketogenesis - mitochondria
Or Phos - mitochondria
GLuconeogenesis - part mitochondria and part cytosol
Urea cycle - part mitochondria and part cytosol
Glycolysis and fatty acid synthesis - cytosol
