High Yield Nutrition and Metabolism

Where does initial fat digestion begin and what enzymes are involved?

Mouth (lingual lipase, gastric lipase); continues in the duodenum of the small intestine

What is the role of bile salts in fat digestion?

Emulsify fat droplets to increase surface area for enzymes and form micelles for absorption

What enzyme breaks down triglycerides in the small intestine and into what products?

Pancreatic lipase; breaks triglycerides into free fatty acids (FFAs) and monoglycerides

What are micelles and what is their function?

Structures where bile salts surround fatty acids, monoglycerides and cholesterol to transport fats through the watery intestinal environment to enterocytes

What happens to fatty acids and monoglycerides inside enterocytes?

They are reassembled into triglycerides, then combined with cholesterol, phospholipids and apolipoproteins to form chylomicrons

What are chylomicrons?

Lipoproteins that transport dietary fat throughout the body

Describe the chylomicron transport pathway from the enterocyte to the bloodstream.

Basolateral membrane → Chylomicron → Lacteal → Thoracic duct → Bloodstream

Where do chylomicrons deliver dietary fat?

Adipose tissue, skeletal muscle and cardiac muscle

What is lipoprotein lipase and what does it do?

An enzyme that breaks triglycerides within chylomicrons into fatty acids and glycerol so fatty acids can enter adipocytes

What happens to fatty acids inside adipocytes?

Fatty acids + glycerol → Triglycerides, stored in fat droplets

What conditions/hormones stimulate lipolysis?

Exercise, fasting, starvation, stress; hormones: glucagon, adrenaline, cortisol

What enzyme mediates lipolysis and what does it produce?

Hormone-sensitive lipase; breaks triglycerides into glycerol + free fatty acids (FFAs)

What is the fate of glycerol produced during lipolysis?

Travels to the liver; used for gluconeogenesis and glycolysis

What is the fate of free fatty acids produced during lipolysis?

Travel bound to albumin; used by muscle, liver and heart for ATP production

What is beta-oxidation and where does it occur?

A process that converts fatty acids into acetyl-CoA; occurs in the mitochondria

Describe Step 1 of beta-oxidation.

Activation: fatty acid → fatty acyl-CoA; uses ATP; occurs in the cytoplasm

Describe Step 2 of beta-oxidation.

Carnitine shuttle: carnitine transports long-chain fatty acids into the mitochondria

Describe Step 3 (each cycle) of beta-oxidation.

Each cycle removes 2 carbons, producing 1 acetyl-CoA, 1 NADH and 1 FADH2

What are the end products of complete fatty acid oxidation?

CO2, H2O, ATP (via: Beta-oxidation → Acetyl-CoA → Krebs cycle → NADH/FADH2 → ETC → ATP + H2O + CO2)

When does ketone body formation occur?

Prolonged fasting, starvation and uncontrolled Type 1 Diabetes

Why do ketone bodies form during starvation?

Excess acetyl-CoA accumulates because oxaloacetate is diverted to gluconeogenesis, slowing the Krebs cycle; the liver converts excess acetyl-CoA into ketone bodies

Name the three ketone bodies.

Acetoacetate, beta-hydroxybutyrate, acetone

Which tissues use ketone bodies and when?

Brain (during starvation), cardiac muscle and skeletal muscle

Describe the VLDL pathway in cholesterol metabolism.

Chylomicron remnants → liver → VLDL (transports endogenous triglycerides) → triglycerides removed → IDL → LDL → cholesterol delivered to membranes

Where does protein digestion begin and what initiates it?

In the stomach; HCl denatures proteins and makes peptide bonds accessible to enzymes

What is pepsin, where does it come from and what does it do?

An enzyme secreted as inactive pepsinogen by chief cells; HCl converts pepsinogen to pepsin which breaks proteins into smaller polypeptides

What activates pancreatic proteases in the small intestine?

Enteropeptidase activates trypsinogen to trypsin; trypsin then activates chymotrypsinogen and procarboxypeptidase

What are the roles of trypsin/chymotrypsin vs carboxypeptidase?

Trypsin and chymotrypsin cleave internal peptide bonds; carboxypeptidase removes amino acids from the carboxyl end

How are amino acids absorbed in the small intestine?

Via sodium-dependent transporters; peptides enter via H⁺-dependent transporters; inside enterocytes peptides are broken into amino acids; amino acids then travel via portal vein to liver

What are the three sources of the body's amino acid pool?

Dietary protein, protein breakdown and synthesis of non-essential amino acids

What enzyme digests starch in the mouth and what does it produce?

Salivary amylase; breaks starch into smaller polysaccharides and maltose

What does pancreatic amylase do and where?

Continues starch digestion into disaccharides in the small intestine

Name the three brush border enzymes and their substrates/products.

Maltase: maltose → 2 glucose; Sucrase: sucrose → glucose + fructose; Lactase: lactose → glucose + galactose

How are glucose and galactose absorbed?

Via SGLT1 (sodium-glucose co-transporter)

How is fructose absorbed?

Via GLUT5 through facilitated diffusion

How do all monosaccharides exit enterocytes?

Via GLUT2 → portal vein → liver

What are the three fates of pyruvate?

1. Aerobic respiration (→ acetyl-CoA → Krebs cycle); 2. Lactate formation (anaerobic); 3. Glucose formation (gluconeogenesis)

When does pyruvate form lactate and what enzyme catalyses this?

When oxygen is limited (exercising muscle, RBCs); catalysed by lactate dehydrogenase; regenerates NAD⁺ for glycolysis

When does pyruvate form glucose and where?

During fasting/starvation; in the liver via gluconeogenesis: pyruvate → oxaloacetate → phosphoenolpyruvate → glucose

Describe the gluconeogenic bypass of glycolysis Step 10 (Pyruvate Kinase).

Pyruvate → oxaloacetate via pyruvate carboxylase (mitochondria; requires ATP and biotin) → PEP via PEPCK (requires GTP)

Describe the gluconeogenic bypass of glycolysis Step 3 (PFK-1).

Fructose-1,6-bisphosphate → fructose-6-phosphate via fructose-1,6-bisphosphatase (cytosol, mainly liver); this is the rate-limiting step of gluconeogenesis

Describe the gluconeogenic bypass of glycolysis Step 1 (Hexokinase).

Glucose-6-phosphate → glucose via glucose-6-phosphatase (ER of liver and kidney cells), releasing free glucose into the bloodstream

Describe Step 1 of glycolysis (Glucose Trapping).

Glucose → glucose-6-phosphate via hexokinase (glucokinase in liver); uses 1 ATP; traps glucose inside the cell

Describe Step 3 of glycolysis (Rate-Limiting Step).

Fructose-6-phosphate → fructose-1,6-bisphosphate via PFK-1; uses 1 ATP; activated by AMP, ADP, fructose-2,6-bisphosphate; inhibited by ATP and citrate

Describe Step 10 of glycolysis (Formation of Pyruvate).

PEP → pyruvate via pyruvate kinase; produces 1 ATP per PEP (2 ATP/glucose); activated by fructose-1,6-bisphosphate; inhibited by ATP and alanine

What is the main function of the electron transport chain (ETC)?

Transfer electrons from NADH and FADH2 to oxygen; pump H⁺ across the inner mitochondrial membrane; drive ATP synthesis via ATP synthase

Where does the ETC occur?

Inner mitochondrial membrane (cristae), between the matrix (low H⁺) and intermembrane space (high H⁺)

Which complex does NADH donate electrons to in the ETC?

Complex I (NADH dehydrogenase); reaction: NADH → NAD⁺ + 2e⁻ + H⁺

Which complex does FADH2 donate electrons to and why does this matter?

Complex II (succinate dehydrogenase); FADH2 bypasses Complex I, so less ATP is produced

What is the role of Coenzyme Q in the ETC?

A mobile carrier that shuttles electrons from Complex I or II to Complex III

Which complexes pump H⁺ into the intermembrane space?

Complex I, Complex III and Complex IV

What is the final electron acceptor in the ETC and what is the reaction?

Oxygen; O2 + e⁻ + H⁺ → H2O (at Complex IV)

How does the proton gradient produce ATP in the ETC?

H⁺ flows back through ATP synthase (Complex V) down its gradient; energy released drives: ADP + Pi → ATP (oxidative phosphorylation)

What is the overall purpose of the Glucose-Alanine Cycle?

Safely transport nitrogen from muscle to liver and return glucose from liver to muscle

Describe the formation of alanine in skeletal muscle (Glucose-Alanine Cycle).

Amino acids undergo transamination → glutamate; glutamate transfers amino group to pyruvate via ALT → alanine + alpha-ketoglutarate

What does alanine carry in the blood during the Glucose-Alanine Cycle?

Carbon skeleton (pyruvate backbone) and nitrogen (amino group)

What happens to alanine in the liver (Glucose-Alanine Cycle)?

ALT converts alanine → pyruvate + glutamate; glutamate releases NH3 (ammonia) → enters urea cycle → excreted in urine; pyruvate → gluconeogenesis → glucose → returned to muscle

What is the Cori Cycle?

A metabolic cycle where muscle produces lactate (from glucose) during anaerobic exercise; lactate travels to the liver; liver converts lactate back to glucose via gluconeogenesis; glucose returns to muscle

How many ATP does glycolysis yield in the Cori Cycle and how much does gluconeogenesis cost?

Glycolysis yields 2 ATP; gluconeogenesis costs 6 ATP (net energy cost to the liver)

How does the Cori Cycle regenerate NAD⁺?

Pyruvate → lactate via lactate dehydrogenase regenerates NAD⁺, allowing glycolysis to continue

What does 1 turn of the Krebs cycle yield from 1 acetyl-CoA?

2 CO2, 3 NADH, 1 FADH2, 1 GTP

How many reactions are in the Krebs cycle and what is the overall purpose?

8 reactions; oxidises acetyl-CoA to CO2, yielding 4 reducing equivalents (3 NADH + 1 FADH2); oxaloacetate is regenerated each cycle