Metabolism of Carbohydrates and Lipids Flashcards
Inhibitors of Complex I (NADH dehydrogenase)
Barbiturate
Piericidin A
Amytal
Rotenone
MNEMONIC: RotenONE acts on complex ONE
Inhibits of Complex II (succinate dehydrogenase)
Malonate
Carboxin
TTFA
Inhibitors of Complex III (ubiquinol:ferricytochrome oxidoreductase)
Antimycin A
Dimercaprol
Inhibitors of Complex IV (cytochrome oxidase)
Cyanide
Carbon monoxide
Sodium azide
Hydrogen sulfide
MNEMONIC: CO blocks CO
Carbon monoxide blocks Cytochrome Oxidase
Three examples of uncouplers
2,4-dinitrophenol
Aspirin
Thermogenin
Complex V (ATP synthase) inhibitor
Oligomycin
Rate limiting step
Glycosis
Phosphofructokinase
Fructose-6-phosphate –> Fructose-1,6-biphosphate
Hexokinase or glucokinase
- Acts at a constant rate to provide glucose-6-phosphate to meet the cell’s need
- High Km
- Activity induced by insulin
- Present in most tissues
- High Vmax
- Hexokinase
- Glucokinase
- Glucokinase
- Hexokinase
- Glucokinase
The transport of reducing equivalents (NADH) from the cytosol to the mitochondria requires this enzyme. It reduces ___ to ___ which then traverse the mitochondrial membrane.
Malate dehydrogenase reduces oxaloacetate to malate, which crosses the mitochondrial membrane from the cytosol to matrix.
In the mitochondrion, oxaloacetate is deaminated to aspartate. In the process glutamate is ‘aminated’ to form a-ketoglutarate. A-KG and Asp then traverses the membrane from the matrix to the cytosol to form oxaloacetate and glutamate. Cycle repeats.
(Malate-Aspartate shuttle)
Reducing equivalents are produced at which step of glycolysis
Glyceraldehyde-3-phosphate -> 1.3-biphosphoglycerate
Glyceraldehyde phosphate dehydrogenase
These organs are strictly glycolytic. The major fate of pyruvate in these organs is to be converted into lactate by lactate dehydrogenase.
- RBC
- Lens
- Cornea
- Kidney (medulla)
- Testes
- WBC
In the human body, pyruvate can participate in:
A. Anaerobic glycolysis, in which it is converted to ___ by ____ (enzyme).
B. Gluconeogenesis, in which it is converted to ___ by ____ (enzyme).
C. TCA, in which it is converted to ___ by ___ (enzyme).
A. Lactic acid, lactate dehydrogenase
B. Oxaloacetate, pyruvate carboxylase
C. Acetyl CoA, pyruvate dehydrogenase
Pyruvate dehydrogenase requires 5-coenzymes:
- Lipoic acid
- NAD+
- FAD
- Thiamine pyrophosphate
- Coenzyme A
In skeletal muscle, glycogen rather than glucose is used for anaerobic glycolysis. Why?
Glycogen can be ‘broken down’ by glycogen phosphorylase to glucose-1-phosphate, which is interconvertible with glucose-6-phosphate. This saves muscle 1 ATP that would otherwise be used by hexokinase (to convert glucose to glucose-6-phosphate). This increases the net yield of ATP from 2 to 3 ATPs per glucose molecule undergoing anaerobic glycolysis.
Why are alcoholics thiamin-deficient?
2 reasons.
- Poor intake
- Alcohol inhibits thiamine absorption
Oxidation of glucose yields up to ___ ATP under aerobic conditions, but only ___ ATP when oxygen is absent.
Aerobic conditions: 38 (or 36)
Anaerobic: 2
When blood samples are taken for measurement of glucose, it is collected in tubes containing FLUORIDE to inhibit glycolysis. Fluoride is an inhibitor of this enzyme.
Enolase
Arsenic poisoning occurs because it reacts with the ____ component of ___.
-SH groups of lipoic acid
Lipoic acid is a cofactor of:
1. Pyruvate dehydrogenase
2. Alpha-ketoglutarate dehydrogenase
Products of glycolysis per glucose molecule.
2 ATPs
2 NADH
3 irreversible and regulated steps in glycolysis
- Phosphorylation of glucose
- Phosphorylation of fructose-6-phosphate
- Formation of pyruvate
2 glycolytic reactions in which substrate level phosphorylation occurred
- Formation of pyruvate
2. Formation of 3-phosphoglycerate
Fluoroacetate is toxic because it inhibits which enzyme of the citric acid cycle.
Fluoroacetate condenses with oxaloacetate to form fluorocitrate which inhibits ACONITASE.
CO2 is released at which steps in the TCA cycle.
Isocitrate > a-KG (Isocitrate dehydrogenase)
a-KG > Succinyl-CoA (a-KG dehydrogenase)
Decarboxylation reactions in TCA require which two cations
Mn++
Mg++
GTP is produced at which step of the TCA cycle
Succinyl-CoA > Succinate (Succinate thiokinase)
Reducing equivalents are released at which steps of the TCA cycle.
NADH (3)
- Isocitrate > a-KG (Isocitrate dehydrogenase)
- a-KG > Succinyl-CoA (a-KG dehydrogenase)
- Malate > Oxaloacetate (malate dehydrogenase)
FADH2 (1)
Succinate > Fumarate (Succinate dehydrogenase)
In tissues capable of gluconeogenesis, the GTP produced in the TCA cycle is used in:
Decarboxylation of oxaloacetate to PEP in gluconeogenesis. This effectively withdraws oxaloacetate from TCA into gluconeogenesis.
Which enzyme in the TCA is also a part of the ETC?
Succinate dehydrogenase (Complex II)
How many ATPs are formed per turn of the TCA cycle?
3 NADH x 3 = 9 ATPs
1 FADH2 x 2 = 2 ATPs
1 GTP
= 12
Is the TCA catabolic or anabolic?
Both. It is amphibolic.
The key enzyme that catalyzes the net transfer out of the TCA into gluconeogenesis
Phosphoenolpyruvate carboxykinase.
Catalyzes oxaloacetate > PEP > Glucose.
GTP used in this reaction
The most important reaction that catalyzes net transfer into TCA cycle.
Carboxylation of pyruvate to form oxaloacetate.
Is acetyl-CoA inhibitory/stimulatory to:
A. Pyruvate dehydrogenase
B. Pyruvate carboxylase
A. Inhibitory
B. Stimulatory. Ensures steady supply of oxaloacetate for condensation with acetyl-CoA.
Which keto-acids are formed by the following amino acids after transamination reactions?
A. Alanine
B. Asparate
C. Glutamate
A. Pyruvate
B. Oxaloacetate
C. Alpha-ketoglutarate
Acetyl-CoA is the major substrate for long chain fatty acid synthesis, which occurs in the cytosol. But pyruvate dehydrogenase which produces Acetyl-CoA is a mitochondrial enzyme. How is Acetyl-CoA made available in the cytosol given that it is impermeable to the mitochondrial membrane?
Acetyl-Coa condenses with oxaloacetate to form citrate (TCA). It is citrate that is transported into the cytosol, and cleaved by ATP-CITRATE LYASE. Citrate is only available for transport out of the mitochondrion when aconitase is saturated with its substrate.