Flashcards in Biochemistry L11/12/13 - Metabolism Deck (43):
What is anabolism and what is catabolism?
Anabolism – to build up. It’s the synthesis of complex molecules in living organisms from simpler ones together with the storage of energy; constructive metabolism.
Catabolism – to break down - the breakdown of complex molecules in living organisms to form simpler ones, together with the release of energy; destructive metabolism.
What can cause variations and adaptations in NORMAL metabolism?
What can cause abnormal metabolism?
- nutritional deficiency
- enzyme deficiency
- abnormal secretion of hormones (i.e. diabetes mellitus)
What are the main metabolic fuels?
Glucose and fats (fatty acids and glycerol), but proteins can also be used.
What are metabolic pathways comprised of?
Enzyme catalyzed reactions usually linked in a series or arrays.
Where does glycolysis occur?
What are the potential products of glycolysis in humans?
- Pyruvate (aerobic conditions)
- Lactate (anaerobic conditions)
What is the molecular formula for glucose?
Name the enzymes used in the 3 main points of regulation of glycolysis. Note: these reactions only proceed in the forward direction.
Reaction: glucose --> glucose 6-phosphate (the first ‘priming reaction’).
A phosphate group is added to glucose using ATP. This is the first step of glycolysis
Reaction: fructose 6-phosphate –> fructose 1,6-biphosphate (the second ‘priming reaction’).
A second phosphate group is added to glucose using ATP. This is the third step of glycolysis
Reaction: Phosphoenolpyruvate –> pyruvate (2ADP are converted to 2ATP. It is the second ATP-forming reaction). This is the last step of glycolysis
Why does the heart muscle survive poorly under conditions of ischemia?
Tissue can survive periods of anoxia because glycolysis can occur in the absence of oxygen. But heart muscle has relatively poor glycolytic ability, so it survives poorly without oxygen.
Why does fermentation occur in the absence of oxygen?
Glucose will still react to form 2 pyruvate molecules, but NADH accumulates in the absence of oxygen and inhibits pyruvate oxidation. Instead, the pyruvate molecules will be converted to lactate (enzyme=lactate dehydrogenase) and will cause NAD+ regeneration.
What are the muscle metabolic systems used during exercise?
- Stored ATP and Creatine-P. Lasts about 8-10 seconds during high intensity exercise.
- Anaerobic glycolysis, yielding about 1.3-1.6 minutes of maximal muscle activity.
Oxygen demand in the mitochondria of muscle cells will eventually exceed the capacity of the blood to deliver it.
- Aerobic system – metabolic reactions taking place in the mitochondria. Occurs during lower intensity exercise. This can keep going until nutrients are depleted.
What is the Cori cycle and why do we need it?
The lactic acid cycle that occurs in the liver. It refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate.
It’s important in preventing lactic acidosis – a low pH in body tissues and blood (acidosis) accompanied by the buildup of lactate. Lactic acidosis also occurs with a deficiency in the enzyme pyruvate dehydrogenase, as pyruvate cannot be turned into acetyl-CoA, and is predominantly transformed into lactic acid.
How is the oxidation of pyruvate to Acetyl-CoA regulated, and which enzyme catalyses this reaction?
Relative concentrations of Pyruvate, Acetyl CoA, NADH and ADP regulate the oxidation of pyruvate.
The reaction is an irreversible reaction catalyzed by Pyruvate Dehydrogenase (PDH). PDH is inhibited by NADH, Acetyl CoA and ATP (the first are products of the oxidation of pyruvate to Acetyl CoA and the second is a product of the ETC).
PHD is activated by ADP and pyruvate.
Which tissues depend predominantly on glycolysis for ATP and why?
Tissues with little or no mitochondria as pyruvate cannot enter the TCA cycle.
Examples: RBCs, cornea, lens, retina, kidney, medulla, testis, leukocytes and white muscle.
What does one cycle of the TCA cycle produce and what is the TCA cycle regulated by?
-3 NADH, 1 FADH2 and 1GTP. It also releases 2CO2.
- Upregulated by ADP, downregulated by ATP and NADH, as well as product down regulation.
What is anoxia and hypoxia and what does it do to the TCA cycle?
Anoxia – complete lack of oxygen supply to tissue
Hypoxia – decreased supply of oxygen in tissue
They lead to total or partial inhibition of the TCA cycle, as it is aerobic.
Why are NADH and FAHD2 important in the Electron Transport Chain (ETC)?
Electrons are transferred from NADH and FADH2 into the ETC and finally to O2 (the terminal electron receptor) to drive the formation of ATP.
How much ATP does a molecule of NADH and a molecule of FADH2 produce?
NADH – 3ATP
FADH2 – 2ATP
What happens to the carbon atoms in glucose after it has been completed metabolized?
They are exhaled as CO2.
What drives phosphate and pyruvate import into the mitochondrial matrix?
What process drives the oxidative phosphorylation of ATP?
Proton Gradient (also known as the electrochemical or voltage gradient).
What is the overall equation of glucose oxidation?
(C6H12O6) + 6O2 + 38 ADP3- +38Pi2- +38H+
= 6CO2 + 6H2O + 38 ATP 4-
What is gluconeogenesis?
Net synthesis or formation of glucose from various substates such as glucogenic amino acids, lactate, pyruvate, glycerol, galactose/fructose
What THREE enzymes are used to bypass the irreversible reactions in glycolysis during gluconeogenesis?
1. Pyruvate carboxylase (pyruvate->oxaloacetate)
2. Fructose-1,6-bisphosphatase (fructose-1,6-biphosphate -> fructose 6 phosphate)
3. Glucose-6-phosphatase (glucose-6-phosphate -> glucose)
Where does the ATP required for gluconeogenesis come from?
beta-oxidation of fatty acids
What are the two PURELY ketogenic amino acids?
Leucine, Lysine - this is because they are converted into acetyl CoA, which cannot be converted back to pyruvate
Can fatty acids be converted to glucose?
What is the process converting stored glycogen into glucose?
What are the two essential fatty acids?
linoleic (omega 6), linolenic (omega 3)
In fatty acid synthesis, what is acetyl CoA initially converted into (commitment step)?
What are 4 factors influencing control of metabolic pathways?
1. Availability of substrates
2. Allosteric activation & inhibition of enzymes
3. Covalent modification of enzymes
4. Induction & repression of enzyme synthesis
During starvation, what substrates does brain use for energy after glucose runs out?
What are some signs of diabetic ketoacidosis?
Hyperglycaemia, Kenonemia, Ketonuria
What are glucogenic amino acids?
Amino acids that can be converted into glucose using carbon skeleton via gluconeogenesis
Which molecule carries FA into the mitochondria?
What products are produced by one round of beta oxidation in the mitochondria?
1 Acetyl CoA, 1FADH2 and 1NADH
Why are triglycerides a more effective energy store than glycogen?
On a weight basis, TAG's yield 2.5x more ATP than glycogen, and they can be stored without water association - glycogen binds about 2x it's weight in water, so you need 3x the tissue weight of glycogen for energy, for the same fat weight.
Fat sources can also last the human body several weeks, while glycogen only lasts about one day
What is the purpose of Urea?
Allows the body to carry ammonia/ammonium in a non-toxic state
From which three pathway intermediates are amino acids synthesized?
Citric acid cycle
Pentose phosphate pathwat
What are the basic metabolic changes in starvation?
-After fasting for a day, most glycogen has been used. The brain can only use glucose or ketones, but needs time to build up the enzymes to allow it to use ketones.
-As you fast, lipolysis is turned on to supply glucose and ketone bodies to the brain. TAGs are broken down into glycerol and FFA. FFA go to the liver to be converted into ketone bodies, glycerol is used in gluconeogenesis
- The ketone bodies generated in the liver go to both the brain, and the muscles, to be used for energy. This has a glucose sparing effect at the muscles, allowing any remaining glucose to be conserved for the brain.
-Skeletal muscle is also broken down (proteolysis) into amino acids, which are used for gluconeogenesis in the liver.
-Any glycogen stores in the body, and any glucose produced by breakdown of glycerol/amino acids, is spent to the brain.
Which metabolic processes occur in the brain?
Glycolysis, Pentose Phosphate Pathway and the TCA cycle.
NO BETA-OXIDATION - the brain cannot use free fatty acids
NO GLUCONEOGENESIS - the brain is reliant on other organs to produce glucose/ketone bodies