Alimentary - Metabolism and Cellular Energy

3.1 Metabolic Concepts & Cellular Energy & 3.2 Catabolic Core of Metabolism Metabolic pathway: ​ Series of steps ​ Catalysed by enzymes ​ → Catabolism: break down, release energy ​ → Anabolism: build, consume energy Common intermediate (activated, limited no.): 3 ​ Glucose-6-phospha...

3.1 Metabolic Concepts & Cellular Energy & 3.2 Catabolic Core of Metabolism Metabolic pathway: ​ Series of steps ​ Catalysed by enzymes ​ → Catabolism: break down, release energy ​ → Anabolism: build, consume energy Common intermediate (activated, limited no.): 3 ​ Glucose-6-phosphate ​ Pyruvate ​ Acetyl CoA Rule of thermodynamics: ​ Spontaneous: exergonic (-ve delta G: Gibbs free energy) ○​ Delta G = G product - G reactant ○​ Create chaos (heat) → release ○​ Only show spontaneity, X indicate reaction rate ○​ Inherent free energy: under same conc., forward / reverse reaction? ​ Set condition: 1M reactant, 25 °C, pH 7 ​ More substrate: delta G more -ve → more spontaneous ​ More product: delta G more +ve → less spontaneous ​ Run towards eqm (delta G = 0) ​ Endergonic (+ve delta G): energy input to drive reaction ○​ Through linked (coupled) exergonic reaction ​ Substrate:product ratio: affect dynamic ​ Essentially irreversible: too exergonic → very favourable Biological reaction: ​ Unfavourable (endergonic, anabolic) driven by favourable (exergonic, catabolic) reaction ​ Overall delta G: -ve ​ Common energy transducer: ATP ○​ Carrier of energy: link catabolism to anabolism ○​ ATP → ADP + Pi: spontaneous, release energy ○​ Pi bond: intermediate amount of free energy ​ 1. PO4 3-: X full resonance → need more energy to maintain shape ​ Taken off → full resonance ​ 2. -ve charge of O2: stressful ​ Break down → release energy ○​ Eg. NADH, NADPH Enzyme: ​ Bind substrate (ligand) @ active site → convert into product ○​ Lock & key model: complementary ○​ Induced fit model: similar shape → change ​ Can de-induce ​ Alternative pathway ​ Lower activation energy (Ea) & delta G → energy input ​ Increase reaction rate ​ Time: direct activity < allosteric < reversible covalent ​ → Allosteric: ○​ Regulatory site: away from active site ○​ Small molecule: bind ○​ → Change conformation of active site ○​ → Promote / inhibit activity ​ → Reversible covalent modification ○​ Regulatory mechanism ○​ Inorganic phosphate (PO4 3-): enzyme phosphorylation → de-phosphorylation ​ Phosphorylation: kinase ​ De-phosphorylation: phosphatase ​ 17000 active genes: 1000 for kinase ○​ → Stimulate / inhibit activity  ○​ Reversible ○​ Hormone: control Key catabolic pathway (respiration): ​ Generate required energy ​ Maintain appropriate energy charge in cell ○​ ~ 70% ATP ○​ ~ 30% ADP ​ ADP → ATP: ~ 5 secs ○​ ATP: exported from matrix ○​ ADP: imported via transmembrane translocase protein ○​ 1 H+ / nucleotide exchanged ​ 4 H+ / P bond generation ​ Enzyme: control flux → Glycolysis: 1. Substrate lv phosphorylation ​ Glucose + 2 (ADP + Pi + NAD+) → 2 (pyruvate + ATP + NADH + H+) ○​ 4 ATP produced ○​ Net production of 2 ATP & 2 NADH ​ Operate most of time in most tissues ○​ Liver & muscle: more control (mass action, allosteric regulation) → more adaptive ​ Liver: metabolism hub ○​ More pathways w/ more control ○​ Eg. hormone ​ Enzyme: ○​ Phosphofructokinase ​ Stimulate: AMP ​ Inhibit: ATP, citrate, H+ (skeletal muscle, pyruvate produce lactic acid → feedback) ○​ Pyruvate kinase ​ Stimulate: fructose-1,6-bisphosphate ​ Inhibit: ATP ​ Emergency reaction: 2 ADP → ATP + AMP ○​ Enzyme: adenylate kinase ○​ AMP: signal for low energy lv 2. Link reaction: ​ Pyruvate → acetyl CoA (→ fatty acid) ​ Enzyme: pyruvate dehydrogenase ○​ Stimulate: pyruvate, Ca2+, insulin ○​ Inhibit: ATP, NADH, acetyl CoA ​ End product regulation ​ Essentially irreversible ​ Cytosolic NADH: donate e- to electron transport chain (ETC) → generate more ATP 3. Citric acid (Krebs) cycle: ​ 2 (acetyl CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O → 2 CO2 + 3 NADH + FADH2 + GTP → 2 H+ + CoA) ○​ Net: acetyl (2-C) → 2 CO2 ​ 4 redox: 4 pairs of e- ○​ 3 pairs: 3 NAD+ + 6 e- → 3 NADH ○​ 1 pair: FAD → FADH2 ​ Aerobic: FAD supply → carry e-s to O2 via ETC ​ Tight regulation: ○​ Allosteric effect on 3 regulated enzymes ○​ Regulate pyruvate dehydrogenase → control of acetyl CoA supply 4. ETC ​ Accept e-s from matrix NADH → gradual release of energy → pump H+ into inner mitochondrial membrane (intermembrane space) ○​ NADH: oxidation of 1 pair of e-s → pump 10 H+s ○​ FADH2: 1 pair → pump 6 H+s ​ pH gradient & transmembrane electric potential → H+ motive force ​ O2: final e- acceptor 5. Chemiosmosis (ATP synthesis) ​ ADP + Pi → ATP ​ Enzyme: ATP synthase ​ ATP synthesis: oxidative phosphorylation ○​ Coupled by H+ gradient ​ 26 (out of 30) ATP generated from 1 glucose Complete oxidation: 30 ATP ​ Glycolysis: 5 (2 direct) ○​ + Cytosolic NADH: 3 ​ 1.5 each ​ pump 6 H+ each ​ Pyruvate dehydrogenase: 5  ​ Citric acid cycle: 20 ○​ Matrix NADH: 15 ​ 2.5 each ○​ Matrix FADH2: 3 ​ 1.5 each ​ pump 6 H+ each ○​ GTP direct: 2 Brain: pump ions (Na+, K+, Ca2+) → burn ATP No. of H+ needed to flow across intermembrane: range ​ Depend on conc. of H+ & ATP Oxidation & phosphorylation: tightly coupled → Uncoupling oxidation: ​ Disrupt H+ gradient → generate heat ​ Eg. non-shivering thermogenesis ○​ Hibernating animal, neonate 嬰兒, mammals adapted to cold ○​ Inner mitochondrial membrane of brown adipose: copies of thermogenin (transmembrane protein) ○​ → Transfer H+ down conc. gradient ○​ Cytosol → matrix ○​ Controlled by hormone ​ Eg. 2.4-dinitrophenol (DNP) ○​ Carry H+ over inner mitochondrial membrane ○​ Dissipate 消散 H+ motive force ○​ Uncoupler: permeable to proteins ○​ Speed up metabolism, use more fat → more energy release ○​ Toxic → used in war as weapon ​ Eg. valinomycin ○​ Inner membrane: K+ permeable ○​ Electrochemical H+ gradient: push K+ into mitochondria ○​ Dissipate change gradient ○​ Much weaker H+ gradient force ○​ Partially affect → X toxic 3.3 Organising Metabolism (DL) Glycolysis: 8 reactions Phosphorylation: ​ Increase chaos (achieve unstable state) → further break down reactions ​ X go back to original cell: locked w/in liver / skeletal muscle / adipose De-phosphorylation: liver, X skeletal muscle ​ Raise blood glucose lv ​ Skeletal muscle: store glycogen (→ glycogenolysis), but X change blood glucose lv Liver: ​ Integrate metabolism → ensure provision of appropriate metabolites under diff. conditions ​ Eating: ○​ Absorb: vitamins ABDK ○​ Metabolise: carb, fat, protein ○​ Alter: glycogenesis, protein → amino acid, fat → fatty acid & glycerol ​ Fasting: ○​ Glycogenolysis: glycogen → glucose ○​ Lipolysis ○​ Beta oxidation ○​ Eg. sleeping Control of metabolic pathways: 3 main tiers ​ Mass action (substrate:product ratio) ○​ Substrate: +ve relationship ○​ Product: -ve ​ Enzyme amount: +ve ​ Enzyme activity: stimulate / inhibit ○​ Allostery ○​ Hormone: insulin secretion after meal → glycogenesis Gluconeogenesis: ​ Convert non-carb → glucose ​ Produce energy ​ Precursor: lipid (fatty acid), protein (amino acid), acetyl CoA, pyruvate, alpha ketoglutarate, oxaloacetate Strict carnivore: ​ Characterised by ketosis state, increased protein oxidation, gluconeogenesis ​ Urea cycle: ○​ Convert NH3 → urea ○​ Remove toxic byproduct (NH3) 3.4 Animals with Simple Stomach Peritoneum, mesentery, omentum: ​ Same structure ​ Diff. region → diff. name GIT development: ​ Single tubular structure ​ In mother’s body: X specialisation ​ Grow & expand → organ ​ Blood supply: aorta → ○​ Coeliac artery (foregut) ○​ Mesenteric artery ​ Cranial (midgut) / caudal (hindgut) Abdominal cavity boundary: line abdomen space ​ Upper: diaphragm ○​ Affect respiration ○​ Bird: thoracoabdominal / coelomic cavity ​ Lower: upper plane of pelvic cavity (floor) ​ Vertical: vertebral column, abdominal muscle Peritoneal cavity / peritoneum: ​ Serous membrane: lining ​ Cover most of intra-abdominal organs ○​ Retro-peritoneum: organ created after peritoneum formation → X cover ○​ Eg. kidneys, pancreas, rectum, part of stomach ​ Composition: ○​ Mesothelium layer ○​ Thin layer of connective tissue (support) ​ Function: ○​ Support organs ○​ Conduit: blood vessels, lymphatic vessels, nerve ​ → Visceral: wrap around organ ​ → Parietal: outer layer, line abdominal & pelvic wall Stomach: ​ Internal anatomy: rugae ○​ Stomach fold ○​ Increase surface area → speed up digestion ○​ Glandular: simple columnar epithelium ​ Wrapped by omentum (peritoneum of stomach) ○​ Extend beyond organ ○​ Double / multiple layer ○​ Greater / lesser curvature → greater / lesser omentum ○​ → Greater: stomach & proximal duodenum → transverse colon & mesocolon  ​ Transverse mesocolon, anterior of intestines: hang down freely ​ Gastrosplenic ligament: connect stomach & spleen ​ Extend: omental bursa → allow stomach to move freely ○​ → Lesser: stomach & proximal duodenum → liver ○​ Only attach to stomach & spleen ​ Benefit surgery ○​ Produce growth factor, increase blood flow, recruit immune cell ​ Cover wound after surgery: speed up healing Coeliac artery: ​ Blood supply to foregut ○​ Liver (hepatic), stomach (gastric), pancreas (pancreatic), spleen (splenic) ○​ → Cranial mesentery ​ Anastomosis (branches connect to each other) ○​ 1 cut off → blood supply still functional ○​ Benefit surgical removal ​ Drainage: hepatic portal vein ○​ Nutrients: small intestine (absorb) → liver → heart → rest of body ○​ Detoxification Liver: Duodenal papilla: ​ Most cranial of abdomen ​ Major: ​ Behind diaphragm ○​ Small opening ​ More towards right ○​ Allow bile & pancreatic juice ​ 6 lobes, 2 processes to flow into small intestine ​ Lobule: hexagon ​ Minor (dog, X cat): ○​ Portal vein ○​ Accessory pancreatic duct ○​ Portal triad ○​ X bile ​ Produce bile ○​ Storage: gall bladder (carnivore) ○​ CCK (hormone): gall bladder contract → release bile Intestine: ​ Small: ○​ Duodenum ​ Lining: secrete mucous & fluid ​ Bile & pancreatic duct ○​ Jejunum & ileum ​ Secrete fluid ​ Digestive & absorptive ​ Large: ○​ Caecum ○​ Ascending / transverse / descending colon ​ Mesentery (peritoneum of intestines) ○​ Double layer ○​ Net of conduit: blood supply ​ Ileocaecocolic junction: ○​ Formed by ileum junction, into ascending colon @ caecocolic orifice ○​ Canine: caecocolic (connect to colon directly) & ileocolic orifice ○​ Feline: ileocaecocolic junction (merge) ​ Everything meet @ once Mesenteric artery: ​ Blood supply to midgut (cranial) & hindgut (caudal)  ○​ Cranial: small intestine, caecum, ascending & transverse colon ○​ Caudal: much smaller, mainly for descending colon (& rectum) ​ Carnivore: longer ​ Anastomosis: ○​ X 1 single vessel / area ○​ Diff. branch → can remove part of intestine Venous drainage: ​ All veins from GIT & spleen: combine into portal vein → liver ​ Filter nutrients: detoxify ​ Distribution into body circulatory system Abdominal wall: muscle ​ External abdominal oblique ○​ Outermost layer ○​ Origin: ​ Costal cartilage ○​ Insertion: ​ Wide aponeurosis (connective tissue: connect muscle & bone) ○​ Fibre direction: ​ Caudoventral ○​ Function: ​ Compress abdominal cavity ​ Trunk rotation ​ Form inguinal ligament ​ Internal abdominal oblique ○​ Origin: ​ Coxal tuberosity ​ Transverse process of lumbar vertebrae ​ Iliac fascia ○​ Insertion: ​ Linea alba ​ Final rib costal arch ○​ Fibre direction: ​ Ventrocranial ​ Perpendicular of external ○​ Function: ​ Compress abdomen (opposite of diaphragm) ​ Oppose external → rotation ○​ Location: ​ Below external, above transverse abdominal muscle ○​ Male: become Cremaster muscle (caudal) ​ Go inside scrotum ​ Maintain temp.: too high → contract → pull away, too low → relax ​ Transversus abdominis ○​ Innermost layer ○​ Origin:  ​ Transverse process of lumbar vertebrae ​ Ribcage ○​ Insertion: ​ Linea alba ○​ Fibre direction: ○​ Transverse ○​ Function: ​ Compress ribs ​ Provide stability ​ Rectus abdominis (6 pack 腹肌) ○​ Origin: ​ Sternum (xiphoid process) ​ Sternal rib cartilage ○​ Insertion: ​ Prepubic tendon ​ Pubic bone (public symphysis) ○​ Fibre direction: ​ Longitudinal on both sides of linea alba ○​ Function: ​ Assist breathing ​ Abdominal stability ○​ Rectus sheath: ​ Tendinous ​ Enclose rectus abdominis ​ Surgery: need to be sutured → provide tension ○​ → Abdominis + sheath → linea alba (white line) ​ Surgery: X blood vessel → place for incision Inguinal ring: ​ Connective tissue opening ​ Between abdominal muscle & aponeurosis ​ (Diff. sex) form passage for vaginal process / descent of testis ○​ Small testicle: pass through → grow → ring close ​ X go back into abdominal cavity ○​ Uterus & cervix: w/in abdominal cavity ​ X use ○​ → Spermatic cord / round ligament ​ X close → hernia (internal of body push through muscle / surrounding tissue wall weakness) ○​ Lobes of intestine can go through ​ Cryptorchidism: ‘missing’ / undescended testicle(s) ○​ Inguinal ring X open enough to allow passage of testicles ○​ Remain inside of abdominal cavity ​ 2 in cavity / 1 in scrotum 1 in cavity ○​ Sometimes fertile ○​ Genetical condition: inherit ​ Remove from breeding pool Abdominal wall: blood supply → Cranial / caudal superficial epigastric artery & vein ​ Very close to skin ​ Cranial: blood supply to mammary gland ○​ Mammary cancer removal: X cut blood vessel Topography (distribution of parts / features w/in organism): 3.5 Gluconeogenesis, Nitrogen Metabolism & Amino Acid Balance Gluconeogenesis: ​ Tissue protein ​ @ liver (+ kidney) ​ Body: glucose deficient ○​ Fasting: amino acid (protein: 3rd energy source), glycerol ○​ Strenuous exercise: lactate ○​ Convert absorbed nutrient: propionate (ruminant) ​ 2nd pathway to increase glucose lv (boost blood glucose lv) ○​ From X CHO metabolic intermediate ​ X simple reversal of glycolysis ○​ Bypass essentially irreversible steps w/ new reaction ​ Consume 6 ATP → need reciprocal control in hepatocyte ​ Enzyme: ○​ Glucose-6-phosphatase: ​ Fructose-6-phosphate → glucose-6-phosphate ○​ Fructose-1,6-bisphosphatase: ​ Fructose-1,6-bisphosphate → fructose-6-phosphate ○​ PEP carboxykinase: ​ Oxaloacetate (4-C in Krebs cycle) → phosphoenolpyruvate ​ Reciprocal ​ Stimulate: glucagon ​ Inhibit: insulin ○​ Pyruvate carboxylase: ​ Pyruvate → oxaloacetate ​ Turn on by acetyl CoA ​ Amino acid: ○​ Glucogenic (pair w/ alpha-keto acid): ​ Alanine: → pyruvate + NH4+ ​ Aspartate: → oxaloacetate + NH4+ ​ Glutamate: → alpha-ketoglutarate (5-C in Kreb cycle) + NH4+ ○​ Ketogenic: ​ → acetyl CoA ​ Regulate: hormone ​ → Neonatal pig:  ○​ Glycogen: supply ~ 1 day of CHO ○​ X gluconeogenic potential for 2-3 days after birth ○​ Suckle milk: fresh glucose ​ X → hypoglycaemic Nitrogen metabolism: ​ Important for health ​ Issue: toxicity ​ Intake as protein (amino acid) ​ → Balance: intake = excretion ​ → +ve: intake > excretion ○​ Eg. growth, pregnancy ​ → -ve: intake < excretion ○​ Eg. starvation ​ Healthy adult: 1 g protein input / day / kg (bodyweight) ○​ Good quality: nutritionally essential amino acid Amino acid pool: ​ Amino group (NH2-) ​ Input: ○​ Endogenous (internal origin) protein ○​ Dietary protein ​ Output: ○​ Endogenous protein ○​ X protein nitrogenous compound ​ Eg. neurotransmitter, catecholamine (stress-responding hormone), nucleotide, heme ○​ Alpha-keto acid ​ Carbon skeleton amphibolic (both cata- & anabolic) intermediate ​ Transamination: amino acid → ​ Deamination: → anabolic synthesis (gluconeogenesis), catabolic energy production ○​ NH3 (toxin) → excretion ​ NH3 (g): ammonotelic (eg. fish) ​ Uric acid: uricotelic (eg. bird, reptile, Dalmatian 斑點狗) ​ Urea (H2N – CO – NH2): ureotelic (eg. mammal) Transamination: ​ Swap R group ​ Form glutamate ○​ Alpha-ketoglutarate →  ○​ Transport into liver ​ Tissue: glutamate + NH4+ ​ Blood (solid transport): → glutamine ​ Liver: → glutamate + NH4+ (deamination) ​ → Urea (urea synthesis / cycle) Urea cycle: ​ Use 4 ATP ​ Produce urea: excretion ​ → Other animal: slow down when fasting ​ → Cat: all time NH3 toxicity: ​ Urea cycle X function → blood NH3 lv rise ​ → NH3 intoxication ○​ Reverse glutamate dehydrogenase ​ Glutamate + NAD+ + H2O ← alpha-ketoglutarate + NH4+ + NADH ○​ Use up alpha-ketoglutarate (Kreb cycle) ○​ Promote: glutamate → glutamine ​ Enzyme: glutamine synthase ​ Clinical sign: ○​ High protein food intolerance, vomiting, mental retardation, coma, death ○​ Genetic defect of urea cycle enzyme, liver disease / damage ​ Treatment: ○​ Lower blood NH3 lv ○​ Low protein diet, small amount & frequent interval 3.6 Energy Stores: Glycogen & Fats Glycogen: ​ Deposit from excess glucose ​ Breakdown: ○​ Liver (80%): buffer blood glucose ○​ Muscle (20%): generate energy during strenuous exercise ​ Storage, X produce ​ Local use ​ Same pathway, diff. hormone: adrenaline (promote phosphorylase) ​ Enzyme: ○​ Glycogen synthase: branching ○​ Phosphorylase: take away 1 glucose ​ Control: reciprocal (1 side on & 1 side off) ○​ Prevent futile (useless) cycle ○​ Allostery ​ AMP (low energy): promote phosphorylase → produce glucose ​ Ca: break down glucose ​ Glucose: promote glycogen synthase ○​ Hormone ​ Pancreas → liver ​ Act on cell-surface receptor → intracellular signal ​ Activate: kinase / phosphatase Insulin Glucagon ​ Promote glycogen synthase ​ Promote phosphorylase ​ Glucose → glycogen ​ Glycogen → glucose ​ Decrease blood glucose lv ​ Increase blood glucose lv Lipid: ​ Triacylglycerol (triglyceride) ○​ 3 long chain fatty acid + glycerol backbone ​ Fatty acid: CH3 – (CH2)n – COOH ​ All single bond: saturated ​ W/ double bond: unsaturated ○​ Primary storage form ​ Predominant: adipose tissue  White Brown ​ Store triglyceride Neonate 嬰兒, small animal ​ Secrete multiple adipokine: ​ Highly oxidative cell-signalling, for body energy ​ Non-shivering thermogenesis status (obesity, inflammation) (uncoupling) Fat droplet Single Multiple, small Mitochondria Few Many Storage Multiple Less (eg. periscapular: shoulder blade) ​ Small amount: liver, muscle ○​ High energy density ○​ Non-polar, X toxic ​ Disease: Species Aberrant 異常 fat: disease All Obesity Cow, sheep Pregnancy toxaemia: body burn fat (X glucose) Cat, horse Hepatic lipidosis: triglyceride accumulate in liver cell Dog, cat Diabetes Human Atherosclerosis (narrowed artery), metabolic syndrome Lipid transport: ​ Liver: metabolism ​ → Fatty acid: bound to albumin (most abundant blood protein), in circulation ​ → Lipoprotein ○​ Classify: size, lipid & protein composition ​ Very low density: newly synthesised triglyceride (liver → adipose tissue) ​ Low density: mixture of lipid (around body) ​ High density: return lipid (other tissue → lipid) ​ Triglyceride: ○​ Absorbed from gut ○​ Chylomicron: facilitate transport through lymphatic system, into blood ​ → Peripheral tissue: metabolism ​ → Adipose tissue: storage (broken by lipoprotein lipase) ○​ Chylomicron remnant: processed in liver ​ Make triglyceride Lipase: ​ Adipose hormone-sensitive lipase: rate control ○​ Promote: glucagon / adrenaline ○​ Inhibit: insulin  Location Function Pancreatic → Small intestine Food lipid digestion Lipoprotein Endothelial cell Hydrolysis Triglyceride Aid tissue uptake Adipose Triglyceride Adipocyte, other (Lipolysis: Stored triglyceride → diglyceride lipid-storing cell release + fatty acid free fatty Hormone-sensitive Diglyceride → monoglyceride + acid) fatty acid Monoacylglycerol Monoglyceride → fatty acid + glycerol Glycerol: ​ → Liver ​ For metabolism Fatty acid: ​ → Cells ​ Free = X esterified (bound) ​ Break down: oxidation ○​ Produce energy ​ Esp. actively metabolising tissue (eg. skeletal muscle) ○​ @ Mitochondrial matrix ○​ → Across membrane: reciprocal regulation ​ Acyl carnitine: facilitate transport via CPT1 transporter ​ Inhibit: malonyl CoA (fatty acid synthesis intermediate) → acyl CoA X transport into mitochondria ○​ → Matrix: beta-oxidation ​ Repeated removal of acetyl CoA ​ Fatty acyl CoA broken down ○​ Palmitate (16-C fatty acid): ​ 7 cycle ​ Generate 8 acetyl CoA (2-C) ​ Net production: 106 ATP / mole (3X of glucose) ​ Synthesis: ○​ @ Liver, adipose tissue ○​ Repeated condensation of acetyl CoA → palmitic acid ​ Acetyl CoA + 7 malonyl CoA + 14 NADPH → palmitic acid + 8 CoA + 14 NADP+ + 6 H2O + 7 CO2 ​ Enzyme: fatty acid synthase (cytoplasmic multi-enzyme complex) ○​ Reciprocal regulation ​ Unique path & enzyme (X reverse beta-oxidation) ​ Site: cytosol (X matrix) ○​ Rate limiting step:  ​ Acetyl CoA + HCO3- + ATP → malonyl CoA + ADP + Pi + H+ ​ Enzyme: acetyl CoA carboxylase Stimulate Inhibit Hormone Insulin: dephosphorylation Glucagon / adrenaline: phosphorylation Allosteric Citrate: feedforward (from external Palmitoyl CoA environment) stimulation AMP: -ve feedback ​ Co-factor: biotin (vitamin B7) ○​ 8 acetyl CoA + 7 ATP + 14 NADPH → palmitate + 8 CoA + 14 NADP+ + 6 H2O + 7 ADP + 7 Pi Lipogenesis: ​ Fatty acid & glycerol → triglyceride ○​ Oppose to adipogenesis (adipose expansion) ○​ Fatty acid: from new synthesis, diet, adipose tissue ​ Mainly @ liver, adipose tissue ​ Pathway: step-wise acylation of glycerol-3-phosphate (from glycolysis) 3.7 Cat Metabolism (DL) Case study ​ 6 months old Persian kitten ○​ Small for its age ​ Poor condition ​ Listlessness 無精打采, walk in circle ○​ After meal ​ Examination: dazed, normal functional cranial nerve Dysfunctional organ system: ​ Digestive ​ Neurological Blood NH3 lv: extremely high ​ Liver deficient ​ Affect urea cycle (deamination & transamination) ​ NH3 intoxication → lower ATP production → listlessness Arginine: ​ Essential amino acid ○​ X fish: excrete NH3 gas ○​ X bird & reptile: excrete uric acid ​ Assist urea cycle (nitrogen metabolism): NH3 → urea Fasting bile acid lv: extremely high ​ Production: break down cholesterol ​ Emulsify lipid ​ Lipolysis: lipid → glucose, produce energy ○​ X produce fatty acid → X beta oxidation ​ Resorption issue Inherited anatomical cause: ​ Portosystemic shunt (PSS) ○​ Blood from portal circulation bypass liver, flow into systemic circulation ○​ Treatment difficulty: depend on type of shunt (tube, allow fluid to move between parts of body) ​ Inter (more difficult) / extra ​ Single / double (more difficult) ​ Hypertension: more difficult ​ X hepatic encephalopathy (structural defect) ​ Diagnosis: ultrasound (muscle) ○​ Bone: X ray Prognosis 預知: bad ​ Depends on type of shunt Treatment: ​ Surgical intervention ○​ Band (metal): slowly close shunt off ○​ Cat: smaller in size → harder ​ Diet: low protein ○​ Omnivore: deal w/ low protein diet more easily ​ Lactulose ○​ Synthetic ○​ Change absorption of protein ​ Antibiotic ○​ Gut flora bacteria ○​ Help w/ protein digestion ​ Low success rate → animal welfare problem Conditionally essential amino acid: ​ Major trauma, stress ​ → Stop production of specific amino acid ​ Need to consume from food 3.8 Oral Cavity & Foregut Point-to-Point Tongue function: ​ Grooming, lapping, prehension, deglutition, vocalisation ​ Taste bud: taste, temp. sensation, mix food w/ saliva Ovine Porcine Canine ​ Main papillae: vallate, fungiform, filiform, foliate ​ Root / body / apex Tongue muscle: ​ Intrinsic ​ Extrinsic ○​ Hyoglossus ​ Attachment: arise from hyoid bone, insert into side of tongue ​ Function: depress & retract tongue ​ Innervation: motor, via hypoglossal nerve (CN 12) ○​ Styloglossus ​ Attachment: originate @ styloid process of temporal bone, insert into side of tongue ​ Function: retract & elevate tongue ​ Innervation: motor, via hypoglossal nerve (CN 12) ​ Lyssa: cup water → drinking Major salivary gland in carnivore: ​ Parotid ○​ Around ear canal ​ Zygomatic ○​ Near eye ​ Mandibular ○​ Behind jaw bone ​ Sublingual ○​ Under tongue Diff. w/ sheep (herbivore): Dog Sheep Size Small Parotid: largest (4 lobes: cranial, middle, caudal, accessory) Zygomatic gland Present X Soft & hard palate: ​ Soft: ○​ Cartilage ○​ Separate oral & nasal pharynx ○​ Breathing, swallowing, speaking ​ Hard: ○​ Bone ○​ Separate oral & nasal cavity ○​ Swallowing, speaking Passage: Food: Air: ​ Upon hard palate ​ Under hard palate ​ Through soft palate ​ Through soft palate ​ Into trachea ​ Into larynx & oesophagus Larynx: ​ Innervate: branches of vagus nerve ​ Laryngeal nerve: ○​ Cranial: 2 branches ​ Internal: innervate mucosa ​ External: innervate cricothyroid muscle → constrict pharynx ○​ Caudal: innervate intrinsic muscle of larynx ​ Except cricothyroid muscle ​ Damage → laryngeal paralysis (horse ‘roaring’) Hyoid muscle: Bone Muscle Cartilage ​ Basihyoid ​ Ceratohyoideus ​ Arytenoid ○​ Single ​ Cricoarytenoid ​ Cricoid ○​ @ base of tongue ○​ Dorsal ​ Epiglottis ​ Ceratohyoid ○​ Lateral ​ Thyroid ○​ Paired ​ Cricothyroid ○​ Rod-shaped ​ Thyrohyoid ​ Epihyoid ​ Hyoepiglotticus ○​ Paired ​ Stylohyoid ○​ Paired ​ Thyrohyoid ○​ Paired ○​ Attach to thyroid cartilage of larynx Muscle of mastication: ​ Digastricus ○​ Jaw opening ○​ Innervation: facial (CN 7) & mandibular branch of trigeminal (CN 5) ​ Temporalis ○​ Jaw closing ​ Masseter ○​ Jaw closing ​ Pterygoid ○​ Lateral (protrude) & medial ○​ W/ masseter: swing motion Teeth: Brachydont: Hypsodont: ​ Crown: above gingiva ​ Erupt throughout life ​ Constrict neck @ gumline ○​ Horse: permanent teeth ​ Root: embedded in jaw bone ○​ Ruminant: cheek teeth ​ X wear → harder ​ Aradicular ​ More spiky ○​ Open root ○​ Continued growth ○​ Eg. rabbit ​ Radicular ○​ Close root ○​ Growth decrease w/ age ○​ Eg. horse ​ Occlusal plate: flat Bird (some species): spike of teeth Diastema: ​ Gap between canine & incisor ○​ Hypsodont: X canine → larger ​ X shorten: ○​ Space for nasal cavity ○​ Muscle attachment ○​ Food move to back when chewing → X need ​ Risk: food get stuck → infection Jaw: bilaterally symmetrical Dental formula: ​ Left → right: ○​ Incisor → canine → premolar → molar ​ Up: maxillary arcade (upper jaw) ​ Down: mandibular arcade (lower jaw) Dog Cat 3142 3131 3143 3121 3.9 Canine Abdomen Dissection: Skin & Body Wall, Topography & Viscera Canine abdomen quiz Aponeurosis: ​ Flat sheet of tendon ​ Collagen fibre: run in same direction Fascia: ​ Flat sheet of connective tissue ​ Collagen fibre: random direction Rectus abdominis: ​ Muscle: ○​ Origin: xiphoid process of sternum ○​ Insertion: public symphysis (public bone) ​ Sheath: ○​ Formed by connective tissue extension of 3 muscles: ​ Transversus abdominis ​ Internal abdominal oblique ​ External abdominal oblique Visceral peritoneum: wrap stomach Epiploic (omental) foramen: ​ Small opening ​ Bounded by hepatic portal vein (central) & caudal vena cava (dorsal) ​ Connect greater & lesser peritoneal cavity ​ Link omental bursa to remainder of peritoneal cavity Coeliac: ​ Ganglion: ○​ Nerve bundle @ upper abdomen ○​ Part of autonomic nervous system  ○​ Innervate digestive tract & abdominal visceral tissue ​ Artery: ○​ Supply oxygenated blood to liver, stomach, abdominal oesophagus, spleen, cranial half of duodenum & pancreas Cisterna chyli: ​ Sac-shaped lymphatic structure ​ Receive lymph from jejunum, ileum, pancreas ​ Through mesenteric lymph node Stomach: 4 regions ​ Cardia, fundus, body, pyloris Oral → ab-oral: ​ Stomach → duodenum → jejunum → ileum → colon → caecum Gall bladder: ​ Between right medial & quadrate lobe of liver Portal vein: ​ Receive venous drainage from spleen, stomach, pancreas, entire GIT ​ Transport to liver for processing