Exam 3 Human Nutrition

Glycolysis is the first step in carbohydrate metabolism and happens in the cytoplasm. Glucose (6C) is transformed into 2 pyruvates (3C x 2).

During the investment stage, 2 ATP are used, a net output of 2 ATP and 2 NADHs are produced. If oxygen is present, then aerobic respiration occurs in the mitochondria and if there is no oxygen present then lactate is produced in the cytoplasm. Aerobic respiration begins with the transition reaction. Pyruvate (3C x 2) is transformed into Acetyl CoA (2C x 2), producing from a single Transition Reaction 1 CO2 and 1 NADH. From 1 molecule of glucose, 2 CO2 and 2 NADH are produced.

The Citric Acid Cycle begins with Acetyl CoA (2C) and Oxaloacetate (4C) to produce Citrate, aka citric acid (6C). 2 CO2, 3 NADH, 1 GTP (which turns into ATP), and 1 FADH are produced in that order from 1 Citric Acid Cycle. There is a total of 2 turns of the Citric Acid cycle producing 4 CO2, 6 NADH, 2 GTP (which turns into ATP), and 2 FADH from 1 molecule of glucose. All of the NADH and FADH generate energy (ATP) through a process called oxidative phosphorylation.

The electrons enter the Electron Transport Chain (ETC) through a series of carriers into the inner mitochondrial membrane. The electrons are passed and ATP is generated. The ETC produces 28 ATP from the electrons. From 1 molecule of glucose, 32 ATP are produced.

Anaerobic respiration occurs in the absence of oxygen. Glucose (6 C) turns into pyruvate (3C x 2) and generates 2 NADH and 2 ATP. Pyruvate (3C) turns into lactate (lactic acid) and converts NADH into NAD so glycolysis can continue. The Cori Cycle technically begins with glucose, which goes to pyruvate and then to lactic acid, like above. Lactate moves from the muscle to the liver. In the liver, lactate goes through gluconeogenesis, which produces a molecule of glucose that then goes back to the muscle to or use as fuel. Only 2 ATP are produced from anaerobic respiration.

Lipid metabolism can be broken down into 5 metabolic pathways: lipolysis, Beta-Oxidation (FA Oxidation), De novo lipogenesis (FA and TG synthesis), Ketogenesis and cholesterol synthesis.

Lipolysis involves cleaving fatty acids from the glycerol by 2 enzymes, LPL and HSL (hormone-sensitive lipase). LPL cleaves FAs from the chylomicron to be taken up in the muscle and adipose tissue. LPL is located in the blood vessels.

HSL is activated by glucagon and epinephrine and deactivated by insulin. HSL mobilizes and cleaves the FAs so they can serve as an energy source if glucose is low. The fatty acids are cleaved and released into circulation and then bind to albumin (transport protein) to be taken to the muscle.

In order for those cleaved fatty acids to produce energy, they have to reach the mitochondria. Carnitine and enzymes (CPT I and CPT II) have to help the FA across the mitochondrial membrane, into the mitochondria. CPT I is located on the outside of the mitochondria and CPT II is located on the inside of the mitochondria.

The fatty acid is activated by CoA, forming Acetyl CoA. Acetyl CoA gets carnitine added by CPT I. Acetyl-carnitine is then transported into the mitochondrial matrix with the help of translocase. The carnitine is removed in the mitochondrial matrix by CPT II. Carnitine is recycled back to the cytosol so it can be used again.

To completely oxidize the FA, 8 cycles of Beta-oxidation have to occur, forming 9 acetyl-CoAs. 8 FADH and 8 NADH are produced and enter the electron transport chain. The 9 acetyl CoAs enter the Citric Acid Cycle and produce 9 GTP, 9 FADH and 27 NADH. The total net ATP produced is 120.

De novo lipogenesis (FA synthesis) needs Acetyl CoA to move out of of the mitochondria. Out of the mitochondria, it is converted to malonyl CoA (3 C) which then attaches to Acetyl CoA to form a 4 carbon fatty acid molecule. This is repeated 7 times to produce a 16 Carbon FA. In Ketone Body Synthesis FAs are used and Acetyl CoA is used by the liver to synthesize ketone bodies.

After they are synthesized in the liver they move into circulation to go to the brain when not enough glucose is present. In the brain Ketone bodies are converted to acetyl CoA which can then enter the citric acid cycle for ATP production.

In cholesterol synthesis acetyl CoA is converted to acetoacetyl-CoA (4 carbons) and then to HMG-CoA. HMG-CoA is converted to mevalonate by the enzyme HMG-CoA reductase.

This enzyme is important because it is the rate-limiting enzyme in cholesterol synthesis. Rate-limiting enzymes limit the rate at which the metabolic process proceeds.

Lipoprotein Lipase is located in the endothelial cells lining the blood vessels in adipose or muscle. LPL cleaves the fatty acids from triglycerides in lipoproteins so fatty acids can be taken up in the tissues. Hormone-Sensitive Lipase is located in adipose tissue. HSL cleaves fatty acids from triglycerides in the adipose so the fatty acids can be released into circulation. The fatty acids bind to albumin, a transport protein to be taken up in the muscles for energy production.

Hormone-Sensitive Lipase is activated by glucagon and epinephrine which maintains the activity level. Insulin decreases the activity level of HSL.

Fatty acid metabolism: Fed State – Food sources exceed the immediate needs of the body. Excess energy is metabolized and stored as dietary triacylglycerols in fat cells. (Anabolic state)

Fatty acid metabolism: mobilization – Occurs during extended exercise because muscles will quickly use up the small amount of stored glycogen, energy stored as fat droplets in adipocytes get mobilized to bring energy reserves to the myocytes. (Catabolic state)

In a fed state which lipolysis enzyme is active, LPL
under mobilization which lipolysis enzyme is active? HSL That’s what I wanted to make sure that you understand in this topic.

Carnitine and CPT enzymes transport fatty acids across the mitochondrial membrane.

When there is not enough glucose, fatty acids are broken down in the liver to form Acetyl-CoA which then is used to produce ketone bodies. Ketone bodies enter circulation and can be exhaled in breath (fruity smell) or be used as a fuel by the brain.

In the brain, ketone bodies are broken back down to Acetyl-CoA to enter the Citric Acid Cycle to produce ATP. If high levels of ketone bodies are produced, ketoacidosis develops, which makes the blood more acidic because the ketones in the blood decrease the pH. It is debatable whether this is harmful, but a fruity-smelling breath is a symptom caused by acetone exhalation.

HMG CoA reductase is important because it controls the amount of cholesterol that is produced. It is the “bottleneck” that limits cholesterol synthesis as the rate-limiting enzyme. Statins are a class of drugs that inhibit HMG CoA reductase and therefore decrease cholesterol synthesis. A decrease in cholesterol synthesis leads to a lower production of LDL and thus could lower the risk of developing cardiovascular disease.

The first step in breaking down amino acids is to remove the amine group. This can either be done by transamination or deamination.

Transamination involves transferring the amine group from an amino acid to a keto acid (AA w/o amine group) to form a new amino acid and keto acid.

Deamination is the removal of the amine group, for example ammonia. The problem with deamination is that too much removed ammonia from the amino acid is toxic. Urea is then produced in the liver by adding CO2 to the 2 ammonias to enter the bloodstream, then to the kidney and then to be safely removed in the urine.

Glyconeogenesis is the production of glucose from a non glucose source. This is almost glycolysis in reverse but with an oxalocetate (intermediate of the Citric Acid Cycle) workaround. FAs cannot synthesize glucose because cannot make pyruvate from acetyl CoA.

Protein degradation and turnover has 3 main systems: ubiquitin-proteasome degradation (1st), lysosome degradation (2nd) and calpain degradation(3rd). U-P degradation involves proteins that are tagged with ubiquitins and inserted into proteasome (trash can) which then get broken down into components.

Lysosome degradation are organelles in the cell that contain proteases, enzymes to digest proteins. Some components can be recycled again. Calpain degradation is not well understood, but it does require calcium.

Transaminase transfers an amino acid to a keto acid. By this process, we can form an amino acid we need from one we have an excess of. Each amino acid has a different "R" side group, so when the amino group is moved from one acid to another, you get a different acid than you started with.

Process where an amino acid is stripped of its nitrogen-containing amino group (NH2). This process occurs in the liver, where the stripped amine group can then be converted to urea and excreted in urine.

Carbon skeletons are what remain after an amino acid has had its amino group (NH3 - Ammonia) removed via deamination or transamination. The ammonia produced is toxic, so urea is formed.
The carbon skeleton is also necessary for glucose. If a keto acid doesn't have any other nitrogens once the amino group is removed, it is a carbon skeleton and can be used to make glucose.

Urea is produced from CO2 and 2 NH3 (Amine groups) in the liver. Urea then enters the blood stream and enters the kidneys. Urea is excreted in the urine. Urea is made as a safe way to keep ammonia levels from getting too high.

Glucogenic amino acids can be used for gluconeogenesis because they form either pyruvate or citric acid intermediates.

Ketogenic amino acids are converted to either acetyl-CoA or acetoacetyl CoA, which can be used to form the ketone bodies acetone or acetoacetate.

Ketogenic amino acids cannot be used in gluconeogenesis because acetyl CoA cannot be used to generate pyruvate.

Alcohol dehydrogenase (ADH) is the major enzyme in alcohol metabolism. ADH converts ethanol and NAD to Acetaldehyde and NADH. ALDH uses NAD, CoA and Acetaldehyde to produce another NADH and Acetyl CoA. When person consumes a large amount of alcohol, the MEOS system is activated to convert some ethanol to Acetaldehyde and to reduce NADPH + H to NADP.

***Which alcohol enzyme is inducible or can increase with increased alcohol consumption?
ALDH because ADH does not change with increased exposure to alcohol.

Liver - gluconeogenesis, alcohol oxidation, ketone body synthesis, Urea synthesis, VLDL synthesis, Glucose-6-Phosphate
Muscle - Glycogen synthesis & breakdown, glycolysis, protein synthesis & breakdown, TG synthesis & breakdown, FA breakdown and lactate synthesis
Adipose - glycolysis, FA synthesis and TG synthesis & breakdown
Brain - glycolysis and ketone body breakdown
RBC - glycolysis and lactate synthesis (needs glucose).