Energy metabolism of major nutrients flashcards
Allosteric enzyme regulation
Intermediate or product binds to site other than the active site and inhibits reactions. Fast and versatile regulation.
What are triglycerides are made of?
3 fatty acids + glycerol
Sources of pyruvate
Glucose, glycerol, and some amino acids
Pathways pyruvate can enter
If anaerobic conditions can be made into 1. Reduced to Lactate (end product of glycolysis) or 2. Converted to ethanol (in yeast and bacteria). If aerobic conditions can be made into 1. Irreversible Oxaloacetate by pyruvate carboxylase (start of gluconeogenesis) or 2. Irreversibly made into Acetyl CoA by pyruvate dehydrogenase complex (PDH) which enters TCA cycle
Steps of PDH
Irreversible, takes place in mitosol 1. Pyruvate enters E1–decarboxylation to yield CO2 and reduces pyruvate to enolic form of acetyl group 2. E2 oxidizes enol into an acetyl group (by reduction of lipoic acid) which attaches to CoA 3. E3 re-oxidizes lipoic acid and reconstructs FAD to allow for the next reaction, produces NADH which goes to terminal oxidation
How many enzymes and coenzymes in PDH?
3 enzymes, 5 coenzymes, and 2 regulatory enzymes
3 products of PDH
Acetyl CoA, CO2, NADH Products also inhibit complex with feedback inhibition
3 reactants in PDH
- Pyruvate 2. NAD+ 3. Coenzyme A (CoASH)
4 forms of regulation in PDH
- Feedback inhibition 2. Phosphorylation and dephosphorylation of enzymes 3. Regulating protein kinase and phosphoprotein phosphatase 4. Calcium
PDH deficiency
Incompatible with life if gone but possible to have reduced activity
What stimulates/inhibits protein kinase?
Stimulates: ATP, Acetyl CoA, NADH Inhibits: Pyruvate (when glycolysis active PDH active)
Congenital lactic acidosis
X linked “dominant” (more common in Ashkenazi jews). PDH mostly inhibited which causes buildup of lactate. May respond to ketogenic (low glucose) diet.
How does glycerol get metabolized?
Converted to pyruvate which becomes Acetyl CoA
How do amino acids get metabolized?
Some converted to pyruvate which becomes Acetyl CoA and some deaminated and oxidized to produce Acetyl CoA directly
3 pathways Acetyl CoA can enter
- Complete oxidation in TCA cycle 2. Conversion into ketone bodies in the liver 3. Biosynthesis of sterols and long fatty acid chains in the cytosol
3 sources of Acetyl CoA (AcCoA)
- PDH 2. Some amino acids 3. beta-oxidation of fatty acids
Why step-wise catabolism of AcCoA?
Highly reduced high energy bond molecule. If we broke it down all at once we would blow up.
Citrate synthase
Reacts with AcCoA to produce isocitrate
How many atoms of C enter Kreb’s cycle? How many lost?
2 C atoms enter, 2 C lost in form of CO2
How many NADH, FADH, and GTP are produced from one turn of TCA cycle?
3 NADH, 1 FADH, 1 GTP
What 3 Kreb’s cycle steps produce 1 NADH each?
- Isocitrate dehydrogenase (also produces CO2) 2. alpha-ketoglutarate dehydrogenase (also produces lipoic acid and CO2) 3. Malate dehydrogenase
What Kreb’s cycle step produces 1 FADH?
Succinate dehydrogenase
What Kreb’s cycle step produces 1 GTP?
Succinyl-CoA-synthase (to Succinate). This uses substrate-level phosphorylation and this step can go back and forth
Energetics produced during TCA cycle?
3 NADH–>NAD+ = 9 ATP FADH2–>FAD = 2 ATP GDP + Pi–> GTP = 1 ATP TOTAL: 12 ATP per acetyl CoA oxidized
5 regulators of TCA cycle
- Supply of AcCoA transport and beta-oxidation of fatty acids 2. Regulation of PDH 3. Supply of NAD+ and FAD 4. Availability of ADP+Pi and oxygen (to make ATP) 5. Regulation of enzymes Rule of thumb: Inhibition downstream means inhibition of everything upstream of it
Arsenic poisoning
Affects enzymes that use lipoic acid as a cofactor (PDH, alpha-ketoglutarate DH)
Fumarase deficiency
Autosomal recessive with reduced enzyme activity and inhibits all steps upstream. Neurological impairment, encephalomyopathy, dystonia.
When there is a need for other nutrients how can TCA cycle be used?
Certain intermediates can go through anabolic reactions to be turned into fatty acids, sterols, amino acids (which can make neurotransmitters), heme (through succinyl CoA to ALA synthase and glycine)
Pyruvate carboxylase
Converts pyruvate to oxaloacetate which is what joins with Acetyl CoA in the first step of TCA cycle. Also main enzyme in gluconeogenesis.
Oxaloacetate
Intermediate of TCA cycle which reacts with Acetyl CoA to produce citrate in the first step of TCA cycle
beta-oxidation
Oxidative degeneration of fatty acids. Fatty acids are cleaved into 2 carbon units to yield Acetyl CoA to enter into TCA cycle. With each cleavage 1 NADH and 1 FADH are formed.
Which enzymes are regulated by Succinyl CoA?
- Citrate synthase 2. alpha-ketoglutarate dehydrogenase (the intermediate comes back to inhibit earlier steps when TCA cycle is full)