AAP2 Exam 4: Metabolism

fats

enter the lymph as chylomicrons; lipoprotein lipase removes them from chylomicrons for uptake by tissues

primary energy substrates for hepatocytes, adipocytes, and muscle cells; most synthesized by the liver is released into the circulation

amino acids (AAs)

most pass through the liver and go on to other cells for protein synthesis

in liver cells, they may be used for protein synthesis, fuel for ATP synthesis, or fatty acid synthesis

absorptive state regulation

regulated by insulin and several intestinal hormones

insulin

regulates glucose uptake by nearly all cells; when cellular uptake increases, plasma concentration falls

stimulates glucose oxidation, glycogenesis, lipogenesis, active transport of amino acids into cells, and protein synthesis; inhibits gluconeogenesis

carbohydrate metabolism

most dietary carbs burned as fuel within hours of absorption

oxidative _____ is glucose catabolism; C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O

function of reaction is to transfer energy from glucose to ATP

glucose catabolism

small steps (each a separate enzyme) where energy is released in small amounts and transferred to ATP (rest is released as heat)

3 major pathways: Glycolysis, Anaerobic fermentation, and Aerobic respiration

glycolysis

glucose split into two molecules of pyruvate; involves phosphorylation

result: NET of 2 ATP; also gives 2 NADH, 2 H⁺, and 2 pyruvate

phosphorylation

hexokinase transfers a phosphate molecule from ATP to glucose = glucose 6-phosphate (G6P), glucose moves into/stays in cells (phosphorylated ≠ permeable)

G6P can be converted to fats, amino acids, glycogen, or energy

anaerobic fermentation

reduces pyruvate to lactate without using oxygen; involves NADH

NADH

donates electrons to pyruvate, reducing it to lactate and regenerating NAD+ (required for glycolysis)

lactate

leaves cell and travels to liver via blood; liver oxidizes it back to pyruvate (O2 required; breathe harder after exercise)

can be converted to G6P, glycogen, and glucose

anaerobic fermentation limits

wasteful process; most energy is still in lactate

cardiac muscle is less tolerant of it (skeletal muscle fine), brain doesn’t use it

aerobic respiration

requires oxygen, oxidizes pyruvate to CO2 + H2O; oxygen is final electron acceptor

occurs in mitochondria, most ATP is generated this way

2 steps: matrix reactions and membrane reactions

matrix reactions

reaction where Acetyl CoA combines with oxaloacetic acid to form citric acid = starts the Citric Acid Cycle

also results in CO₂, NADH, and FADH₂

controlling enzymes are in fluid of the mitochondrial matrix

membrane reactions

oxidize NADH and FADH₂ further into ATP, and regenerate NAD⁺ and FAD; carried out by the mitochondrial ETC

controlling enzymes are bound to membranes of mitochondrial cristae

electron transport

during ___, hydrogen atoms are split apart as they transfer from coenzymes to the chain

protons are pumped into the intermembrane space

electrons

travel in pairs along transport chain

each ____ carrier becomes reduced when it receives an ____ pair, then oxidized again when it passes them along to the next carrier

oxygen

final electron acceptor; accepts 2 electrons from cytochrome and 2 protons (H+) from mitochondrial matrix, making water (primary source of metabolic water)

chemiosmotic mechanism

H⁺ current rushing back through ATP synthase channels drives ATP synthesis; ETC energy fuels respiratory enzyme complexes.

results: CO₂, H₂O, 32 ATP

coenzymes

donate hydrogens to other compounds in reaction pathways

glycolysis + fermentation steps

1. Phosphorylation (Glucose, G6P)

2. Priming (Fructose 6-phosphate, Fructose 1,6-diphosphate)

3. Cleavage (2PGAL)

4. Oxidation (2 NADH + 2H⁺)

5. Dephosphorylation (2 pyruvate)

new proteins

cells make them by drawing upon the AA pool, which comes from dietary proteins and tissue protein breakdown (100g / day total)

some AAs are converted to glucose, fat, or fuel; conversion involves 3 processes: deamination, amination, and transamination

deamination

removal of an amino group (NH₂); allows proteins to be used as fuel

keto acid remains, which is converted to pyruvate, acetyl CoA, or one of the acids in the CAC

reactions are reversible in case there is an amino acid shortage

ketoacids

used to synthesize glucose in gluconeogenesis

amination

addition of an amino group (NH₂)

transamination

transfer of NH₂ from one molecule to another

when an AA is deaminated, it forms glutamic acid, which travels to the liver, where it can make ammonia, which SHOULD NOT accumulate

urea cycle

ammonia and CO2 combine to produce less toxic waste and urea (excreted in urine)

protein synthesis

involves DNA, mRNA, tRNA, and ribosomes

stimulated by growth hormone, thyroid hormone, and insulin, and requires a supply of all amino acids

nonessential amino acids

made by the liver from other amino acids or CAC intermediates

essential amino acids

must be obtained from the diet

glycogen metabolism

extra glucose is converted to other compounds better suited for energy storage, like glycogen (energy storage molecule) and fat (RJ)

glycogenesis

synthesis of glycogen, stimulated by insulin; chains glucose molecules together

glycogenolysis

hydrolysis of glycogen, stimulated by glucagon and epinephrine

liver cells release glucose cells back into blood, which provides glucose between meals

gluconeogenesis

synthesis of glucose from non-carbohydrates, such as glycerol and amino acids

occurs mainly in the liver, but also the kidneys if necessary

lipid metabolism

continual turnover of lipids in the body as they are synthesized from energy storage (lipogenesis) or used for fuel (lipolysis)

lipogenesis

synthesis of fat from other types of molecules (like AAs, sugars) which make fatty acids and glycerol

PGAL is converted to glycerol, and acetyl CoA is used to make fatty acids

lipolysis

breaking down fat for fuel; triglycerides are hydrolyzed into glycerol (converted to PGAL) and fatty acids (converted to acetyl CoA)

stimulated by epinephrine, norepinephrine, glucocorticoids, thyroid hormone, and growth hormone

beta oxidation

occurs in the mitochondrial matrix; catabolizes fatty acid components

fatty acid with 16 C’s = 129 ATP molecules (richer energy source than a glucose)

fatty acids can also enter the CAC as Acetyl CoA, or undergo ketogenesis

rapid or incomplete ___ raises blood ketone levels; can cause ketoacidosis

ketogenesis

the liver makes ketone bodies from fatty acids

absorptive (fed) state

about 4 hours during and after meal

nutrients are being absorbed, and are used to meet energy and other needs

postabsorptive (fasting) state

prevails in late morning, late afternoon, and overnight

stomach and intestine are empty, and energy needs are met by stored fuels

plasma glucose concentration= 90-100 mg/dL; critical for the brain

postabsorptive carbohydrates

____ (glucose) is drawn from glycogen reserves or synthesized from other compounds

liver glycogen can last 4 hours until gluconeogenesis occurs

postabsorptive fats

adipocytes and hepatocytes hydrolyze ___ and convert glycerol to glucose (used for brain)

free fatty acids ≠ glucose, but can affect plasma concentration; instead oxidized into ketone bodies (used by non-brain cells)

postabsorptive proteins

used as fuel when glycogen and fat reserves are depleted; can result in cachexia

cachexia

extreme wasting away, seen in some chronic diseases, caused by anorexia and altered metabolism

postabsorptive regulation

via sympathetic nervous system and glucagon (secreted by pancreatic cells)

when blood glucose drops, insulin secretion drops

glucagon

pancreatic hormone that promotes glycogenolysis + gluconeogenesis, lipolysis and rise in FFA levels

raises blood glucose level, makes glucose and lipid available for fuel

sympathoadrenal system

a physiological connection between SNS and adrenal medulla

promotes glycogenolysis and lipolysis, especially under stress

cortisol

released under stress; promotes fat and protein catabolism and gluconeogenesis