Cell Metabolism 1

Question 1

What are the 6 types of metabolic reactions?

Answer 1

1. Oxidation/Reduction - involves electron transfer
2. Group Transfer - involves transfer of functional group from one molecule to another
3. Ligation requiring ATP cleavage - Formation of a covalent bond
4. Addition/Removal of Functional Groups - groups added to a double bond or a double bond formed from removal of groups.
5. Hydrolytic - Cleavage of bond by addition of water.
6. Isomerization - Rearrangement of atoms to form isomer.

Question 2

What enzymes are characteristic of specific metabolic reactions?

Answer 2

Dehydrogenases carry out redox reactions. Isomerases carry out isomerization reactions. Kinases carry out phosphate group transfer reactions.

Question 3

What are the three fates of pyruvate?

Answer 3

Can form ethanol through alcoholic fermentation. Can form lactate and acetyl CoA.

Question 4

How does alcoholic fermentation occur?

Answer 4

Pyruvate decarboxylase forms acetaldehyde which then forms ethanol through action of alcohol dehydrogenase. This regenerates NAD+ and allows glycolysis to continue so ATP can be generated.

Question 5

How does lactate production occur? Acetyl-CoA?

Answer 5

Through action of lactate dehydrogenase. Acetyl CoA is formed through action of pyruvate dehydrogenase complex along with HS-CoA substrate which also forms carbon dioxide. Poor PDC function results in Beri-Beri.

Question 6

What causes Beri-Beri and what are its symptoms?

Answer 6

Beri-Beri is caused by a thiamine deficiency - thiamine is a cofactor of the pyruvate dehydrogenase complex as its carbanion attacks pyruvate. Hence Acetyl CoA not formed from pyruvate which has consequences on metabolism and respiration. Symptoms are: weak musculature, PNS damage, decreased cardiac output and brain damage as it relies heavily on glucose metabolism.

Question 7

What is the output of each TCA cycle?

Answer 7

2 carbon dioxides, 3 NADH, 1 GTP and 1 FADH2

Question 8

What are the 8 key steps of the TCA cycle?

Answer 8

1. Acetyl CoA joins with oxaloacetate to form 6C citrate
2. Citrate is converted to isocitrate in a 2 step process (removal and then addition of water mol)
3. Isocitrate is oxidized and releases molecules of CO2 leaving behind 5C alpha-ketoglutarate.

Question 9

What are the 8 key steps of the TCA cycle?

Answer 9

1. Acetyl CoA joins with oxaloacetate to form 6C citrate
2. Citrate is converted to isocitrate in a 2 step process (removal and then addition of water mol)
3. Isocitrate is oxidized and releases molecules of CO2 leaving behind 5C alpha-ketoglutarate. NAD+ is reduced to NADH. Isocitrate dehydrogenase important to regulate speed of process.
4. Alpha-ketoglutarate is then oxidised in reaction catalysed by alpha-ketoglutarate dehydrogenase - NAD+ reduced to NADH and CO2 released. 4C molecule picks up a CoA forming unstable succinyl CoA.
5. CoA of succinyl CoA replaced by a phosphate group which is later used to form an ATP from an ADP (or a GTP) forming succinate.
6. Succinate oxidised to fumarate and 2H atoms with electrons transferred to FADH forming FADH2. Enzyme catalysing this buried in inner membrane of mitochondrion so FADH2 can directly transfer electrons to ETC.
7. H20 added to fumarate converting it to malate.
8. Oxaloacetate regenerated by oxidation of malate - NAD+ is reduced to NADH.
   Phosphoenolpyruvate can convert this oxaloacetate to glucose.

Question 10

What are transamination reactions?

Answer 10

The transfer of an amine group from one amino acid to a keto acid through action of enzymes known as aminotransferases, generating a new pair of amino and keto acids.

Question 11

What does the degradation of all 20 amino acids lead to?

Answer 11

The formation of 7 molecules: Pyruvate, Acetyl CoA, Acetoacetyl CoA, Alpha-ketoglutarate, Succinyl CoA, Fumarate, Oxaloacetate

Question 12

How can amino acids enter the TCA cycle?

Answer 12

Amino group is removed and excreted as urea while carbon skeleton is funneled into glucose production or Krebs cycle. Ketogenic amino acids enter at acetyl CoA or acetoacetyl CoA stage while glucogenic amino acids enter elsewhere.

Question 13

What does fatty acid metabolism produce and where are fats derived from?

Answer 13

Fatty acid metabolism produces acetyl CoA. Fats are derived from the diet, de novo synthesis in the liver and storage in adipose tissue.

Question 14

What is the purpose of bile salts?

Answer 14

Fats are insoluble so require bile salts to be absorbed by the gut. Bile salts are created by the liver and stored in the gallbladder. Also aid the absorption of fats and fat-soluble vitamins like 2,7,9 and 10. Lack of bile salts leads to steatorrhea (fatty, oily stools).

Question 15

What is orlistat?

Answer 15

Drug that inhibits gastric and pancreatic lipases, reducing fat absorption by 30%. Can be used as treatment for obesity for up to 2 years. However, can have adverse side effects such as abdominal pain.

Question 16

What are the different type of lipoproteins?

Answer 16

1. Chylomicrons, made in intestines, role is lipid transport
2. VLDL, formed in the liver, role is endogenous fat transport.
3. IDL, formed from VLDL, role is LDL precursor
4. LDL, formed from IDL, role is cholesterol trasnport
5. HDL, formed in the liver, role is reverse cholesterol transport.

Question 17

Describe process of lipid transport from lumen of ileum to cell

Answer 17

Digested dietary fat is absorbed by enterocytes lining the brush border of the ileum. Triglycerides are resynthesized and incorporated into chylomicrons which are released. It is then transported in the lymphatic system from the lacteal to the thoracic duct, left subclavian vein and finally into bloodstream. In the bloodstream, chylomicrons pick up apoprotiens from HDL. Lipoprotein lipase found on capillary endothelial cells in adipose tissue+heart+skeletal muscle tissue attach to the apoproteins. Beta oxidation of fatty acids occurs and glycerol is returned to the liver along with rest of chylomicron. On way back, rest of apoprotein returned to HDL.

Question 18

What are the effects of HDL and LDL?

Answer 18

HDL is good lipid and takes cholesterol back from peripheral tissue to liver for use or disposal. Lowers total serum cholesterol.
LDL is bad lipid as it doesn’t lower serum cholesterol and chronically elevated levels of LDL lead to atherosclerosis.

Question 19

What are lipoproteins?

Answer 19

Phospholipid monolayers containing cholesterol apoproteins, surrounding core of cholesterol ester and triacylglycerols.

Question 20

What are the 5 types of lipids?

Answer 20

Free fatty acids, Triacylglycerols, Phospholipids, Glycolipids, Steroids.

Question 21

What is beta oxidation and when is it used?

Answer 21

Process of fat metabolism which produces over 50% of body’s energy. Fatty acids are ultimately converted to acetyl CoA in the mitochondria and used to produce ATP. This predominates during times of fasting biut when fat metabolism occurs during fasting, acetyl CoA needs equal amount of carbohydrate metabolism to form the oxaloacetate. If there is none, acetyl CoA converted to ketone bodies and it doesn’t enter TCA cycle.

Question 22

Describe process of beta oxidation

Answer 22

Firstly fatty acids are converted to an acyl CoA species by acyl-CoA synthetase, requiring hydrolysis of an ATP to an AMP. The generation of this acyl CoA species occurs in the outer mitochondrial membrane and so to transport species into the matrix, carnitine shuttle used. Inside matrix, acyl CoA undergoes cycle of hydration, oxidation and thiolysis. Produces one acetyl CoA and 1 acyl CoA which is 2 carbons shorter. Process repeats 7 times in total. Acetyl CoA can then enter TCA cycle if oxaloacetate present.

Question 23

Describe action of carnitine shuttle

Answer 23

Acyl CoA species donates acyl group to carnitine, catalysed by carnitine acyl transferase-1, forming acyl carnitine outside mitochondrial matrix. Acyl carnitine can then move into matrix via a translocase in the matrix membrane. Inside the mitochondria, acyl group transferred back to a CoA species forming acyl CoA once again. Carnitine formed in a reaction catalysed by carnitine acyl-transferase 2.

Question 24

What is the beta oxidation reaction equation?

Answer 24

Palmitoyl CoA + 7 FAD + 7 NAD+ + 7H20 + 7 CoA forms
8 Acetyl CoA + 7 FADH2 + 7 NADH

Each FADH2 produces 2 ATP, Each NADH produces 3 ATP and each Acetyl CoA produces 12 ATP so net is 131 ATP (adjusted for ATP used up in initial processes to form compounds)

Question 25

What is formed when fat metabolism predominates?

Answer 25

Acetyl CoA forms ketone bodies such as acetoacetate, D-3-hydroxybutyrate, and Acetone.

Question 26

Describe lipogenesis

Answer 26

Fatty acids are formed sequentially by decarboxylative condensation reactions involving acetyl CoA and malonyl CoA. Following each round of elongation, fatty acid undergoes reduction and dehydration by sequential action of ketoreductase (KR), dehydratase (DH) and enol reductase (ER) activity. Growing fatty acyl group is linked to an acyl carrier protein (ACP).

Question 27

Describe fatty acid degradation process

Answer 27

Activated acyl group undergoes oxidation, hydration, oxidation and cleavage to form an activated acyl group shortened by 2 carbons and an activated acetyl group

Question 28

Contrast fatty acid synthesis and degradation

Answer 28

Degradation requires a CoA carrier, uses oxidation with FAD/NAD+ being reduced and takes place in the mitochondrial matrix. Synthesis requires an ACP carrier, uses reduction with NADPH and takes place in cytoplasm.

Question 29

How are fatty acids longer than 16 carbons formed?

Answer 29

Elongation of fatty acids to lengths longer than 16C occurs separately from palmitate synthesis in mitochondria and endoplasmic reticulum. Desaturation of fatty acids requires action of fatty acyl-CoA desaturases. Enzyme that creates palmoleic acid from palmitate known as delta-9 desaturase as it generates a double bond 9 carbons from terminal carboxyl group.