Biochemistry 4: Low-Carb Diets Flashcards
What is the mechanism for weight loss in low-carb diets?
Insulin increases fatty acid synthesis (via activation of acetyl-CoA carboxylase, the key regulated step of fatty acid synthesis), and inhibits lipolysis (via inhibition of hormone-sensitive lipase). Insulin is released in proportion to the amount of sugar processed by the pancreatic beta cells, so by restricting carbohydrates → insulin release ↓ → fatty acid synthesis ↓ / lipolysis ↑ → fat loss
How can you make sense of insulin’s effect on hormone sensitive lipase?
Insulin inhibits hormone sensitive lipase (involved in breaking down triglycerides to release the fatty acids – these fatty acids can be metabolized into acetyl-CoA in other cells in the body).
In states of low blood sugar → insulin ↓ → HSL ↑ → fatty acid release ↑ → acetyl-CoA production ↑ → ketone body production ↑ → brain fuel in low-sugar states
Why do you measure ketosis as a measure of effectiveness of low-carb diets?
The hallmark of low-carb diets is to severely reduce the amount of insulin released by the pancreas → glucagon ↑ → ketogenesis
What is the refined carbohydrate hypothesis and why does it make sense?
Sugar/carbohydrates are rare in nature. As such, the pancreas “evolved” to use carbohydrates as a proxy for how much we ate, to know how much insulin to release. However, as we refined carbohydrates → insulin release ↑↑↑ → obesity
A 12-year-old boy is brought in after being found unresponsive in his room. His mother reports that he had been unusually hungry over the past several weeks, but that he had seemed to be losing weight. His pulse is 130/min, respirations are 28/min and heavy, and blood pressure is 70/40. Physical examination demonstrates cool, dry skin, and a 2/6 murmur heard best at the apex. He is unresponsive to voice but withdraws to painful stimulus.
Lab studies demonstrate:
Serum:
Na+ 125 mEq/L
K+ 5.4 mEq/L
HCO3- 5 mEq/L
Urea nitrogen 91 mg/dL
Glucose 874 mg/dL
Creatinine 4.2 mg/dL
What is the pathophysiologic chronology?
12 yr ♂ → Born with predisposition to developing T1DM (polyphagia, losing weight) → Previously diagnosed and non-compliant with meds or 1st presentation in newly diagnosed → insulin AND amylin ↓ → disinhibition of glucagon release → Hyperglycemia (in DKA) →:
- Glucose Filtration by glomeruli → Overwhelms PCT re-absorptive capacity → Excess glucose in PCT → ↑ Fluid and Solute arriving in LoH → Osmotic diuresis → Loss of water and solutes incl. glucose and K+ → Dehydration with no intake/repletion → ↓ preload → ↓ SV → ↓ CO → ↓ MAP →:
a) ↓ Baroreceptor stretch/reflex → ↑ reflex sympathetic tone ↑ → ↑ HR, systemic vasoconstriction (cold, clammy) / speed of blood flow through valves ↑ → flow murmur
b) ↓ Cerebral perfusion pressure → ↓ Cerebral flow → ischemia → ↓ GCS
c) Renal hypoperfusion → ↓ GFR (SNS output overrides autoregulation) → ↓ Cr and BUN filtered but ↑ Urea absorption → BUN:Cr > 20 + no casts or non-specific hyaline casts (Tams-Horsfall proteins)
d) RAAS activation → ↑ Free water and Na+ absorption
e) ADH release → Free water re-absorption in CDs probably inefficient due to loss of corticopapillary gradient
- ↑ plasma osmolarity →:
a) Draws free water out of cells together with K+ (solute drag) + ↑ intracellular [K] → ↑ K+ diffusion out of cells → HyperK+ (masking a ↓ in total body K+)
b) Dilutes Na+ (hypertonic hypoNa)
- But glucose not being taken up by cells due to ↓ Insulin →:
a) ↓ glycolysis → ↓ ATP production → ↓ NaKATPase activity → less K+ taken in → Contributes to HyperK
b) Fatty acid oxidation aggressively stimulated (↑↑↑ glucagon with no insulin) to generate Acetyl CoA → Ketogenesis → Ketoacidosis (low bicarb, also contributing to low GCS) → Peripheral and Central Chemoreceptors triggered by ↑ H+ → Hyperventilation with heavy breathing [Kussmul’s Breathing] to blow off CO2 → Compensatory Resp. alkalosis + Fruity acetone breath (ketones sponataneously breakdown into Acetone)
c) No stimulation of Acetyl CoA Carboxylase → No fatty acid synthesis
- Hyperglycemia contributes to ↓ GCS
