Bioenergetics, OxPhos, metabolism overview - NYIT

Question 1

Cellular respiration

Answer 1

Harnessing ATP out of oxygen and energy serviced from oxidized fuels

Question 2

Reducing equivalents

Answer 2

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)

Question 3

ETC

Answer 3

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

Question 4

ETC Inhibitor

Answer 4

causes rate of respiration to decrease, reduction of proton gradient and ATP synthesis and ATP concentration

Question 5

ETC uncoupler

Answer 5

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

Question 6

Thermogenesis

Answer 6

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)

Question 7

Structure and function of mitochondria

Answer 7

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

Question 8

ATP-ADP exchange

Answer 8

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.

Question 9

What is Valinomycin effect on the ETC?

Answer 9

ETC uncoupler

It is an ionosphere antibiotic

Disrupts the proton gradient by causes the transport of K+

Question 10

Cyanide poisoning and detoxification

Answer 10

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)

Question 11

DNP - 2,4, dinitrophenol

Answer 11

Uncoupler of ETC

Antiseptic, collapses ATP gradient? Or pH?

Question 12

How does Roteenone and Amytal effect the ETC?

Answer 12

ETC inhibitors

ROtenone - common insecticide

Amytal - depresses the CNS, typically used as a sedative or anticonvulsant

Question 13

Complex III inhibitor

Answer 13

Antimycin A - inhibits electron transfer at complex III

An antibiotic substance produced by streptomyces

Question 14

Approximately how much energy is harnesses from fats, carbohydrates and protein?

Answer 14

Fats - 9Kcal/gram

Sugars/Proteins - 4Kcal/gram

Once burned it stays, so whatever isn’t utilized for metabolic energy is stored in adipose

Question 15

What molecule can be considered a common point among most, if not all, metabolic pathways?

Answer 15

Acetyl CoA

from pyruvate out of glycolysis through pyruvate dehydrogenase

From fatty acids (citrate, triaclyglycerol) and alpha-kept-acids (amino acids)

Question 16

General glycolysis

Answer 16

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

Question 17

What is lactic acidosis? Why does it happen? What are the physiological responses?

Answer 17

.

Question 18

Describe amino acid catabolism, what does it produce?

Answer 18

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

Question 19

Fatty acid breakdown

Answer 19

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)

Question 20

Ketosis and ketoacidosis: causes, source, site of utilization, associated clinical correlates?

Answer 20

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

Question 21

How is energy stored long term in the body?

Answer 21

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

Question 22

Pentode Phosphate Pathway

Answer 22

Generation of NADPH

Production of ribose 5-phosphate

Question 23

Insulin

Answer 23

Produces by beta cells of the pancreas

Most active after eating, stimulate cellular uptake of glucose

Stimulates glycogenesis and protein synthesis, lipid synthesis

Question 24

Glucagon and epinephrine

Answer 24

Produced by pancreatic alpha cells

Mobilizes - most active during fasting

Increases glycogenolysis and gluconeogenesis

Stimulates lipolysis

Acts to raise blood sugar levels

Question 25

Corticosteroids and Thyroid hormones

Answer 25

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)

Question 26

FED State

Answer 26

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

Question 27

FAST state

Answer 27

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

Question 28

Starvation State

Answer 28

low insulin
High glucagon

Glycogen is depleted

Fatty acids from fat are released into blood

Question 29

Major metabolism in the Brain

Answer 29

active and metabolically expensive (~20% of O2 at rest)

Free glucose

Uses ketone bodies during periods of starvation only

No glycogen

Question 30

Major metabolism in muscle

Answer 30

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

Question 31

Metabolism in adipose tissue

Answer 31

Lipolysis while fasting

Lipogenesis when fed

Question 32

Metabolism in the Liver

Answer 32

Nutrient absorption through hepatic portal vein

All metabolic pathways involve the liver

Fasting: glycogenolysis, gluconeogenesis, ketogenesis

Fed: glycogenesis and lipogenesis

Question 33

Where do you find beta-oxidation, ketogenesis, Oxidative phosphorylation, gluconeogenesis, urea cycle, glycolysis and fatty acid synthesis within a cell?

Answer 33

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