Biochemistry 21 and 22 Flashcards

Fatty acid oxidation primarily takes place in the mitochondria of heart, skeletal muscle, and liver cells.

Fatty acid elongation occurs in three cellular compartments: the cytosol, mitochondria, and endoplasmic reticulum (ER).

Cytosol:

• In the cytosol, fatty acid elongation involves the addition of carbon atoms to existing fatty acids.
• The process uses malonyl-CoA as a chain extender.
• The resulting elongated fatty acids contribute to various cellular functions.

Mitochondria:

• Mitochondria can also participate in fatty acid elongation.
• However, the starting materials for mitochondrial elongation are generally shorter than 16 carbons.
• Mitochondrial elongation is less common compared to other compartments.

Endoplasmic reticulum:

• The ER is a major site for fatty acid elongation.
• Using the same set of enzymes as other fatty acid synthesis steps, the ER elongates fatty acids.
• Unlike cytoplasmic synthesis, the elongation process in the ER is separate and not part of a complex.
• Propionyl-CoA is used instead of acetyl-CoA for elongation beyond 16 carbon-chain fatty acids.

Fatty acid synthesis occurs in the cytoplasm of the cell.

Fatty acid desaturation occurs in the endoplasmic reticulum (ER) of the cell.

Cholesterol synthesis primarily occurs in the cytosol of liver cells.

Cytoplasmic face of membranes of the endoplasmic reticulum

mitochondria of the liver

Through the pentose phosphate pathway and by malic enzyme

(it says that I don't really need to know the enzymes and such but I think I should know the names it would make it easier to explain)

(note: I will need to know all the reactions, all enzyme names, all cofactors, all substates and products)

1) acetyl-CoA is converted into malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC)

2) ACP bind to both acetyl-CoA and malonyl-CoA

3) The phosphopantetheine group of ACP interacts with the substrates, forming acetyl-ACP and malonyl-ACP

4) These loaded ACP molecules serve as carriers for the acetyl and malonyl groups during the elongation process

5) Then these go to fatty acid synthesis

1) acetyl-CoA is converted into malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC)

2) ACP bind to both acetyl-CoA and malonyl-CoA

3) The phosphopantetheine group of ACP interacts with the substrates, forming acetyl-ACP and malonyl-ACP

4) These loaded ACP molecules serve as carriers for the acetyl and malonyl groups during the elongation process

5) Then these go to fatty acid synthesis

ACC controls pools of malonyls-CoA:

1) inhibition of beta oxidation

2) ACC activates lipid biosynthesis

3) ACC influences lipid storage and mobilization

glucagon, epinephrin, high AMP trigger phosphorylation/inactivation, Palmitoyl-CoA

citrate

• Palmitate is the precursor.
• Desaturation involves introduction of double bonds into existing fatty acids
• Human cells can only desaturate fatty acids before the 10th carbon.
• Fatty acid with double bonds near the ends is essential because we can't synthesize them.
• This occurs in the smooth endoplasmic reticulum.
• Human cells lack delta-12 and delta desaturates. We can thus only consume essential omega-3 and omega-6 fatty acids

eicosanoids = signaling molecules derived from PUFAs (including arachidonic)

COX = enzymes responsible for converting AA into eicosanoids

1) Cox-1 = regulates the production of prostaglandins, which play a role in platelet aggregation and mucosa acid production

2) Cox-2 = is present in kidneys, brain, and bones. It contributes to inflammation.

(Don't worry about structures)

• By activating lipogenic enzymes
• stimulates ACC leading to conversion of acetyl-CoA into malonyl-CoA (building block of fatty acid synthesis)
• Insulin enhances uptake of glucose in fat tissue which combines to male triglycerides.

2 precursors = fatty acyl-CoA and L-glycerol 3-phosohate phosphatic acid

Phospholipid Synthesis:

1. Starts with adding a fatty acid to glycerol 3-phosphate.
2. This creates lysophosphatidic acid.
3. All cells make phosphatidylcholine (PC) via the CDP-choline pathway.
4. Choline entering the cell is quickly changed to phosphocholine.

Triglyceride Synthesis:

1. Made by all cells, but mainly in the intestines and liver.
2. Uses NADPH for the reactions.
3. NADPH comes from the Pentose Phosphate Pathway and the malic enzyme.
4. Triglycerides are made from fatty acyl-CoAs and glycerol-3-phosphate.

1. When glucose is scarce: This process is used when the concentrations of glucose in the cell’s cytoplasm are low1.
2. Precursors: The main precursors of glyceroneogenesis are pyruvate, lactate, glutamine, and alanine1.
3. Key enzyme: The main regulator enzyme for this pathway is an enzyme called phosphoenolpyruvate carboxykinase (PEPC-K), which catalyzes the conversion of oxaloacetate to phosphoenolpyruvate1.
4. Where it happens: Glyceroneogenesis is observed mainly in adipose tissue, and in the liver1.
5. Why it’s important: Intense suppression of glyceroneogenesis may lead to metabolic disorders such as type 2 diabetes1.

1. Pyruvate to Oxaloacetate: Pyruvate is converted into oxaloacetate by the enzyme pyruvate carboxylase.
2. Oxaloacetate to Phosphoenolpyruvic Acid (PEP): Oxaloacetate is then converted into PEP by the enzyme PEP carboxykinase.
3. PEP to Dihydroxyacetone Phosphate: PEP is converted into dihydroxyacetone phosphate through a series of reactions in the glycolysis pathway.
4. Dihydroxyacetone Phosphate to Glycerol 3-Phosphate: Dihydroxyacetone phosphate is converted into glycerol 3-phosphate by the enzyme triose phosphate isomerase.
5. Glycerol 3-Phosphate to Triglyceride Synthesis: Glycerol 3-phosphate is used as a backbone in the synthesis of triglycerides.

1. Regulates Fatty Acid Release: During periods of fasting, glyceroneogenesis modulates the release of fatty acids. When fuel is not available from the diet, lipolysis releases glycerol and fatty acids from triglyceride stores in fat cells1.
2. Triglyceride/Fatty Acid Cycle: Glyceroneogenesis is part of the triglyceride/fatty acid cycle, which includes local intracellular cycling within the adipose tissue and extracellular or systemic recycling. This cycle accounts for a considerable quantity of fatty acid recycling2.
3. Prevents Metabolic Disorders: Intense suppression of glyceroneogenesis may lead to metabolic disorders such as type 2 diabetes23.
4. Maintains Energy Balance: As well as synthesizing lipids for use in other metabolic processes, glyceroneogenesis regulates lipid levels in the cytosol

1. Induction of PEPC-K in the Liver: Corticosteroids induce the transcription of phosphoenolpyruvate carboxykinase (PEPC-K), the main regulator enzyme for glyceroneogenesis, in the liver1.

(meaning it would downregulate gluconeogenesis)

1. Decrease of PEPC-K in Adipose Tissues: At the same time, corticosteroids decrease the transcription of PEPC-K in adipose tissues1.

This dual action of corticosteroids helps to regulate the balance of lipid metabolism between the liver and adipose tissues.

Stage 1: formation of mevalonate from acetyl-CoA

General overview:

1. Acetyl-CoA to Acetoacetyl-CoA: Two molecules of acetyl-CoA combine to form acetoacetyl-CoA1.
2. Acetoacetyl-CoA to HMG-CoA: Acetoacetyl-CoA is converted into 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by the enzyme HMG-CoA synthase1.
3. HMG-CoA to Mevalonate: HMG-CoA is reduced to mevalonate by the enzyme HMG-CoA reductase. This is the rate-limiting step in cholesterol synthesis23.
4. Mevalonate to Isopentenylpyrophosphate (IPP): Mevalonate is converted into IPP2.
5. IPP to Squalene: IPP units are joined together to form squalene2.
6. Squalene to Cholesterol: Squalene undergoes a series of reactions to form cholesterol2.

1. Lipoproteins: Lipids are transported in the bloodstream as lipoproteins. These exist as several variants with different functions, protein and lipid compositions, and densities.
2. Exogenous Pathway:
   • Dietary lipids are packaged into chylomicrons.
   • Fatty acids from TAG are released by lipoprotein lipase to adipose and muscle tissues during transport through capillaries.
   • Chylomicron remnants (which contain largely protein and cholesterol) are taken up by the liver.
   • Bile salts produced in the liver aid in dispersing dietary fats and are then reabsorbed in the enterohepatic pathway.
3. Endogenous Pathway:
   • Lipids synthesized or packaged in the liver are delivered to peripheral tissues by VLDL.
   • Extraction of lipid from VLDL gradually converts some of it to LDL.
   • LDL delivers cholesterol to extrahepatic tissues or returns to the liver.
4. Reverse Cholesterol Transport: Excess cholesterol in extrahepatic tissues is transported back to the liver as HDL.

1. Cholesterol Transport: Cholesterol is transported from liver into the bloodstream by lipoproteins such as LDL and VLDL1.
2. LDL Receptor-Mediated Endocytosis:
   • The LDL receptors on the cell surface bind to LDL particles in the blood¹.
   • This forms a complex that is internalized into the cell in a process called endocytosis¹.
   • The complex forms a vesicle inside the cell, which then fuses with a lysosome¹.
   • The lysosome contains enzymes that break down the LDL, releasing the cholesterol inside the cell¹.

1. Regulation of Cholesterol Synthesis:
   • The synthesis of cholesterol is regulated by an enzyme called HMG-CoA reductase2.
   • When there’s enough cholesterol in the cell, this enzyme is inhibited, which reduces cholesterol synthesis1.
   • At the same time, the cell reduces the number of LDL receptors, which decreases cholesterol uptake1.
   • If cholesterol levels are low, the cell increases the number of LDL receptors to take up more cholesterol from the bloodstream1.

1. Familial Hypercholesterolemia (FH): It’s an autosomal dominant disorder, meaning you only need one copy of the faulty gene from either parent to develop the condition.
2. Gene Mutations: The condition is most commonly caused by mutations in the LDLR gene. Less common are mutations in the APOB and PCSK9 genes.
3. LDL Receptor Function: The LDLR gene makes a protein that binds to LDL in the blood and carries it into cells where it’s broken down.
4. Effect of Mutations: Mutations in the LDLR gene lead to an abnormal LDL receptor. LDL particles aren’t effectively removed from the bloodstream, leading to high levels of LDL cholesterol.
5. Other Genes: Mutations in the APOB gene affect the structure of apolipoprotein B, a protein that binds to the LDL receptor. PCSK9 gene mutations lead to an increase in the number of LDL receptors that are broken down in the cell, reducing the number available to clear LDL cholesterol from the bloodstream.
6. Resulting Condition: The end result is high levels of circulating LDL cholesterol, which can lead to the formation of fatty deposits in the arteries, a condition known as atherosclerosis.

1. Cholesterol Removal: HDLs remove cholesterol from tissues and transport it back to the liver.
2. Inhibition of LDL Oxidation: HDLs prevent the oxidation of LDLs, reducing the formation of harmful foam cells.
3. Anti-Inflammatory Properties: HDLs limit the inflammatory processes that underlie atherosclerosis.
4. Antithrombotic Properties: HDLs prevent the formation of blood clots, which can lead to heart attacks and strokes.

Steroid hormones:

• Testosterone and estrogens = help development of sex characteristic
• Aldosterone = increases blood sodium levels
• cortisol = regulates metabolism, helps with immune response

Thyroid hormones:

• stimulates basal methanolic rate

Vitamin D:

• regulates calcium and phosphate metabolism

(will need to know the image included)

why its needed:

• nitrogen is a major elemental constituent of living organisms.
• atmosphere is 80% N2, but in Nonuseful form.
• can allow use of renewable energy sources.
• all about converting N2 to NH3, NO2-, or NO-

Don't need to draw but I think that is the best option

Porphyrin rings = makes up the heme of hemoglobin, cytochromes, myoglobin (important in Jaundice)

phosphocreatine = important energy buffer om skeletal muscle

glutathione = thought to be a redox buffer

impaired liver (liver cancer or hepatitis)

blocked bile secretion (due to gallstones, pancreatic cancer)

insufficient glyceryl bilirubin transferase to process bilirubin (occurs in infants, UGTs)

not breaking down heme

mood and depression involvement

#1 reward center

#2 ability to move the muscles (Parkison's don't make dopamine so they can't move muscles)

invovles in thermoregulation signals to the brain

used for adrenalin

signals to liver and muscles

fight or flight hormone

treats seizers

inhibitory transmitter

allergic response, acid secretion in stomach (H2 blocker)

Glucose comes from amino groups.

Glycine is a precursor for purines

asparagine is a precursor for pyrimidines

pyrimidines

purines

amino groups

(don't need to know how to draw but I think it is the best way to memorize it)

adenylate kinase - AMP + ATP <---> 2 ADP

guanylate kinase - GMP + ATP <----> GDP + ADP

nuclease diphosphate kinase = uses various donors of the phosphate group

GDP + ATP <---> GTP + ADP

delta G = 0

roundabout pathway ...

1) dUTP is made

2) dUTP --> to dUMP by dUTTPase

3) dUMP --> dTMP by thymidylate synthase (target for anti-cancer drugs, no DNA replication = can't divide cells then can't grow)

-adds a methyl group from tetrahydrofolate