Aerobic Metabolism 1 The Citric Acid Cycle (TCA) Flashcards
What is the main cite in our cells where aerobic respiration takes place?
Mitochondria
What are the processes of aerobic metabolism?
1) citric acid cycle (Acetyl-CoA “pyruvate under aerobic condition”, “fatty acid breakdown”, “some amino acids”)
2) electron transport chain
3) oxidative phosphorylation
With their important intermediate being NADH & FADH2
What are the coenzymes in the aerobics metabolism?
1) NAD, NADP (from the vitamin niacin, nicotinic acid), their oxidized form is NAD+ (Involved in biosynthetic reactions) & NADP+ (involved in catabolic reactions), and their reduced form is NADH & NADPH
2) Riboflavin (vitamin B2) two examples functioning as dehydrogenases, oxidases, and hydroxylases
- Flavin mononucleotide (FMN)
- Flavin adenine dinucleotide (FAD “usually permanently attached”)
3) CoenzymeA acyl carrier molecule
What is the structure of NAD?
Benzene with fused Nitrogen, and an amide and adenosine
What is the structure of FAD & FMN?
1) FAD is riboflavin + adenosine
2) FMN is riboflavin + phosphate
Riboflavin has a isoaloxazine which is a component of riboflavin that accept and donate electrons
What is the structure of coenzyme-A?
Adenosine + 4-phosphopantetheine (pathonic acid (vitamin derived) + B-mercaptoethylamine (which is important as it contains sulfur))
What are the steps in the citric acid cycle?
In the mitochondrial matrix
conversion of pyruvate (3-carbon) into Acetyl-CoA (2-carbon) releasing CO2, NADH & H+ using pyruvate dehydrogenase “biggest enzyme, contains 3 enzymes, requires 5 coenzymes, requires two regulatory enzyme” (utilizing NAD+ & CoASH)
1) interaction of oxaloacetate with acetyl-CoA to form citrate using H2O producing CoASH via citrate synthase (regulatory step “condensation reaction”) its accumulation indicates high energy
2) conversion of citrate into isocitrate via aconitase (isomerization)
3) oxidation of isocitrate to a-ketoglutarate via isocitrate dehydrogenase producing NADH, H+, & CO2 (regulatory “oxidative decarboxylation”)
4) oxidation of a-Ketoglutarate into succinyl-CoA producing NADH, H+, & CO2 via a-ketoglutarate dehydrogenase (regulatory “oxidative decarboxylation”)
Now the aim is to produce oxoaloacetate for the cycle to keep going
5) cleavage of succinyl-CoA into succinate via succinyl-CoA synthetase (substrate level phosphorylation reaction “associated with ATP production”) producing GTP which will convert ADP into ATP
6) succinate is oxidized to fumarate via succinate dehydrogenase producing FADH2 (occurs in the inner mitochondrial membrane)
7) fumarate is hydrated into malate H2O via fumarase
8) malate is oxidized into oxaloacetate producing NADH + H+ via malate dehydrogenase
What is pyruvate dehydrogenase complex?
It is the largest enzyme in the body, composed of three enzymes
1) pyruvate dehydrogenase/decarboxylase (E1) which requires the coenzyme (TPP, Thiaminepyrophosphate “acetyl carrier”) “decarboxylate pyruvate converting it to acetyl, releasing CO2”
2) dihydrolipoyl transacetylase (E2) which requires the coenzymes (Lipoic acid, & CoASH) “transfer the acetyl group from HETPP to CoenzymeA releasing acetyl CoA with the help of lipoic acid”
3) dihydrolipoyl dehydrogenases (E3) which requires (NAD+ & FAD) “reoxidize dihydolipoamide to lipoamide to be used again for the reaction, releasing NADH”
This enzyme catalyzes the conversion of pyruvate to acetyl CoA
The net reaction is (oxidative decarboxylation):
Pyruvate + NAD+ + CoASH = acetyl-CoA + CO2 + NADH + H+
What connects the TCA cycle to gluconeogenesis?
Oxaloacetate
What are the products of the TCA cycle?
1) production of 3 NADH (reaction 3, 4, 8)
2) production of FADH2 (reaction 6)
3) production of ATP (reaction 5)
4) 2 CO2 released (reaction 3, 4)
What is meant by amphibolic?
That the TCA cycle can be used as both catabolic and anabolic pathway
1) citrate can be inverted into oxaloacetate + acetyl-CoA which can be used to synthesize cholesterol and fatty acids
2) a-ketoglutarate can be converted into glutamate used for protein biosynthesis
3) succinyl-CoA can be used for the synthesis of heme and chlorophyll when we add certain fatty & amino acids to it
4) oxaloacetate can be converted to aspartate (protein biosynthesis), can be used for pyrimidines (nucleotide synthesis), used to synthesize glucose
How is the TCA cycle regulated?
1) enzymes 1) citrate synthase (inhibited: succinyl-CoA, Citrate, NADH & ATP), 2) isocitrate dehydrogenase (Inhibited: NADH & ATP Stimulated: NAD+ & ADP), 3) a-ketoglutarate dehydrogenase (Inhibited: succinyl-CoA & NADH)
2) two reactions: 1) the reaction forming acetyl-CoA from pyruvate “pyruvate dehydrogenase complex” 2) conversion of pyruvate to oxaloacetate by pyruvate carboxylase
3) Ca2+ increase can increase ATP Via activating the enzyme which regulates the speed of the TCA cycle (isocitrate dehydrogenase & a-ketoglutarate dehydrogenase as it binds to a regulatory site on each enzyme)
4) citrate accumulation in the cytoplasm inhibits glycolysis (via inhibiting PFK-1)
What are the diseases associated with the citric acid cycle?
Rarely but theses diseases are caused by a deficit in citric acid cycle enzyme:
A) Most common forms are forms of encephalopathy, which are linked to mutations in:
1) a-ketoglutarate dehydrogenase
2) succinate dehydrogenase
3) fumarase
4) succinyl-CoA synthetase
B) Several rare cancers
What are the products of the TCA cycle?
1) reduced coenzymes 1) Nicotinic acid (NAD (catabolic reaction) & NADP (biosynthetic reaction)), 2) Riboflavin ((component of FMN & FAD), FUNCTIONS IN dehydrogenases, oxidases & hydroxylases)
2) NADH (donated to the ETC)
3) FADH2 (donated to the ETC)
4) CO2
What is the TCA cycle used for?
Harvest energy from acetyl group (derived from the catabolism of carbohydrates, lipids & some amino acids) of acetyl-CoA carried by CoenzymeA
