2: Water, Acids, Bases and Buffers Major Body Components

Water Characteristics: How Many Molecules can it Bind to?

3-4

Bicarb/HCO3- in ECF or ICF? and why?

(ECF) acts as a major buffer in the blood and helps regulate blood pH, so it is more concentrated in the ECF where it plays a key role in maintaining acid-base balance.

Phosphatidyl choline

Phosphatidyl choline (lecithin) helps by acting as an emulsifier. It stabilizes fat droplets in water increase the surface area for digestive enzymes to break down dietary fats more efficiently.

Lipases

To digest these fats, they need to be broken down into smaller droplets. As fat droplets get smaller, their surface area increases, allowing lipid-digesting enzymes (lipases) to access and break down more of the fat.

Ion product of Water is Related to what Property of Water?

Self-Ionization into hydroxyl/hydrogen ions

Kw

1.0^-14 and H⁺/OH⁻ concentration is 1.0^-7 mol/L at pH = 7

H+ and OH- concentrations should add up to what?

1*10^-14

Buffers are ____ acids

weak

A weak acid can ___ or ___ a proton

donate or accept

An Acid Donates A Proton Rxn (water accepts protons from acids)

H₂O + HA ↔ H₃O⁺ + A⁻

Sulfuric Acid Rxn (what is it classified as)

B-hydroxybutyric acid (what is it classified as ) rxn

Acetoacetic acid (what is it classified as) rxn

Strong Acid ; H₂SO4 --> 2H⁺ + SO4(2⁻)

KB; gives up its H from COOH in KB ↔ (KB)with COO⁻ + H⁺

CB: B-hydroxybutyrate

KB; does the same as above KB

CB: acetoacetate

pka indicates

the willingness of acid to donate a proton

pKa of sulfuric acid - completely disassociated, COOH is 3.8 and Ammonium is 9.25

Water donates protons to bases

H₂O + B (ammonium NH3) ↔ BH⁺ (NH4+) + OH⁻

Ammonium at physiological pH tendencies

HH Equation

pH = pka + log (CB/A)

pH = pKa @ 50% diassociation where [A-] = [HA]

pka - strong acid has a low pka and high Ka

Ka = [H+][CB or A-] / [HA} with more being on top if SA

Buffer Resist Change (OH- added)

for +1 pKa: Acetate (removing protons) drops off protons from COOH to make water (from OH+H) to resist a rise in pH.

Acetic acid is all found in the acetate form at one above pKa so no more H+ to give to OH- so no more buffer

Typically: HA --> H+ + A- & OH- + H+ --> H2O keeps Ka constant

Buffer Resist Change (OH- removed or acid added)

for -1 pKa: reducing OH- ions trying to lower pH but acetic acid counteracts that by sucking in H+ ions.

Typically: H+ + A- --> HA to keep Ka constant

At pH of 7.4, what form will acids be in?

Anion; 50-50 around 4.5: dotted line is 7.4 ish. Clear where its all CB in anion form.

At pH = 7.4 what form would ammonium (NH4+) be with pka of 9.25 and dihydrogen phosphate with pKa of 6.8

NH4+ --> NH3 + H+ (it would be in its ammonium NH4+ form)

Dihydrogen:monohydrogen phosphate: 50-50

Hemoglobin is what and functions where

minor buffer in RBC and plasma

Bicarbonate is what and functions where vs phosphate buffer system

Its in CB form. Formula for carbonic acid: H2Co3. In intracellular fluid, you have phosphate buffer system which is major buffering system in ICF. H2PO4 can give up both protons but it only like to give up 1 proton and pKa for giving up one proton is 6.8.

Bicarbonate System

CO2: weak acid and buffered

Carbonic anyhdrase makes carbonic acid (H2Co3) from CO2+water.

Exhale Co2 so more bicarbs formed. pKa = 6.1 close to 7.4 good things.

At a pH of 7.4, still find mostly carbonic acid since more than 1 pH unit away from the normal physiological pH of 7.4. To get a pH of 7.4 with an apparent pKa value of carbonic acid, we have to have a ratio of 20 bicarbonates for every carbonic acid.

Metabolic Acidosis

Increased [H+] OR decreased [HCO3-]
Decreased pH
- Ketosis
- Kidney damage
- Chronic diarrhea
- Excessive lactate production —> tissue hypoexia

Metabolic alkalosis

Decreased [H+] OR increased [HCO3-]
Increased pH
- Prolonged vomiting
- Excessive ingestion of antacids

Carbonic anhydrase role in RBC, renal tubules, parietal cells, and pancreatic cells

Carbonic anhydrase imp in RBC, renal tubules (excretion/reabsorption of bicarbonate), parietal cells (stomach acid HCl formation by bicarb cells), pancreatic cells (bicarb to SI for a buffer of stomach acid)

Bohr curve (in relation to carbonic anyhdrase)

Buffer acids/bases affects hemoglobin ability to bind to o2. Low CO2, low H+, decrease temp - left shift hemoglobin saturation curve (increased affinity of hemoglobin for o2).

Left shift (less CO2 and H+): less dissolved oxygen to reach same percent saturation so we increase hemoglobin affinity for O2

Right shift (elevation in CO2, H+): decreased affinity. More dissolved o2 to reach same hemoglobin saturation.

Red Blood Cell Mechanism (in relation to carbonic anyhdrase) "CO2 a weak acid"

High CA in RBC: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻

Hemoglobin buffers H⁺ (until it must bind O₂ → ↓ H⁺ buffering → right-shift O₂ curve).

Phosphate buffer exists but is weaker; overwhelmed → hemoglobin takes over.

CO₂ from metabolically active tissues enters RBC, converted by CA, HCO₃⁻ exchanged out to carry more H⁺.

Extra H⁺ can also come from ketone bodies or lactic acid

Hepatic Cell Mechanism

In hepatic cell, we have generic protein acting as a buffer to bind to protons and phosphate buffering system to make dihydrogen phosphate instead of mono.

Bicarb major buffer system in ECF. Proteins, phosphate buffer system inside cells. Hemoglobin/proteins/carbonic anhydrase/bicarb in RBC.

Physiological pH Range

Blood pH is slightly alkaline (7.3-7.4). Bc its slightly alkaline, when we say patient is in acidosis, it doesn't mean blood pH below 7. Its just below reference range. When a patient has alkalosis condition, the pH is above reference range.

Resp Acidosis

Increased H+ | PCO2 | HCO3-
Lower pH

- Pneumonia

- Emphysema

- Severe asthma

- Acute pulmonary

- Congestive heart failure

- Drug inhibition of respiratory center —> ethanol/barbiturates

Metabolic Alkalosis Cause

Decreased [H+] OR Increased [HCO3-] High pH | High PCO2.

Rare

- Prolonged vomiting

- Excessive ingestion of antacids

Resp Alkalosis

Decreased [H+] OR Decreased HCO3-, decrease pCO2, Increased pH

increased CO2 elimination. Hyperventilation, high latitude leads to it.

Patient case

Type 1 Diabetes and KB - can't process dietary sugar due to type I diabetes so metabolizes fats for energy --> KB synthesis. Main ketones are acetoacetic acid and b-hydroxybutyric acid.

D/L AA and Sugars

L AA and D sugars.

Choline

quaternary amine

FA+glycerol

acetyl-coA

peptide bonds

nucleic acids

triphosphate of NTP

ester

thioester

amide

phosphoester bonds

acid anhydride

Vitamin A (structure and function in night blindness)

11-cis retinal (aldehyde)

When light hits that cis double bond, that provides enough energy to isomerize into a trans double bond.

Cis → trans changes conformation, starts cascade, electrical impulse to brain → light. Thats how eyes sense the presence/absence of light. Patients with Vitamin A deficiency have night blindness.

Retinoic Acid

Another form of vitamin A is Retinoic acid (all trans). It ends with COOH group (not an aldehyde). All double bonds in trans position not cis. This form of vitamin A functions (not a steroid hormone - similar) as steroid hormone transcription function ligand. Binds to transcription factor to reg expression of diff genes. Diff genes - vitamin binds to diff transcription factor that reg expression of other genes.

Vitamin A Transport

The aldehyde form, retinaldehyde, circulating form in blood is alcohol form retinal, storage form conjugated to FA is retinyl esters, functional groups dictate why/how vitamin A is functioning in diff tissues

Vitamin A oxidation-reduction

Oxidation-reduction : alcohol retinol form → oxidize to aldehyde → oxidize it further to COOH

Sorbitol (glucitol) - glucose

Sorbitol is what builds up and causes cataracts and neuropathy retinopathy in patients with diabetes. If we have sm glucose around for so long, an alternative metabolic pathway for glucose is to make sorbitol. Great for dealing with glucose but next rxn that takes sorbitol to fructose is slowed. Sorbitol builds up, act as a solute, put water in tissues with eyes and causes retinopathy/cataracts/neuropathy - cells to die.

Alt pathway for glucose and normal pathway to make fructose - patients with diabetes with sm glucose - alt pathway to make sorbitol n sorbitol rxn slow so sorbitol hangs for too long.

Used as a sugar substitute, laxative (hyperkalemia) (Sorbitol acts as a laxative because it is not fully absorbed in the intestine. When consumed in excess, it remains in the gut, where it draws water into the intestines through osmosis. This increased water content helps soften stools and stimulates bowel movements, leading to its laxative effect.)

galactitol (dulcitol) - galactose

Same thing with galactitol. Here talking abt patients with galactosemia - can't metabolize galactose. Galactitol builds up in eye and causes cataracts in young patients since milk primary food source. Lactose made up of galactose n glucose - can't metabolize glucose. Only galactitol can't metabolize it further → pulls water in lens of eye and causes cataract in 18 month patients.

Mannitol (mannose)

Mannitol used as osmotic diuretic. Can't metabolize mannitol cuz sugar alcohol - pulling water to reduce pressure in eyes n cranium for glaucoma.

Fructose

ketone sugar

Glucose and galactose

aldose sugar (aldehyde)

Retinol/aldehyde/sorbitol/galcitol oxidation vs fructitol

Retinol oxidized to retinaldehyde being further oxidized to COOH form - remember that. IF we oxidized aldose sugars, we get COOh. If we reduce aldehyde, we get an alcohol. Sugar alcohols like sorbitol or galictol - not a fructitol. Not able to reduce ketone to alcohol. The aldehyde reduced to aldehyde and get sugar alcohol.

aldose reductase

aldehydes and reducing back to alcohol is by aldose reductase enzyme that takes aldehyde sugars and makes alcohol

Glucose to glucuronic acid

oxidation to make fat soluble --> water soluble molecules (usually 2 of them added). Put it on bilirubin (2 glucuronate molecules on it) to make it more soluble. To get rid of Vitamin A, conjugate to glucuronic acid and secrete it in urine.

Get rid of vitamin A

conjugate to glucuronic acid and excrete in urine

Additions to sugars

Phosphate addition (glucose-6-phosphate) - traps glucose in cell if phosphorylated!!

Ring Structures are _____. Alpha - Beta?

Carb found as ring structure. Hydroxl group on first carbon dictates whether its an alpha or beta sugar. If OH below, alpha sugar. If above, beta sugar.

Lactose linkage is ______

beta 1,4 : galactose + glucose

Lactase as u get older

it goes down

alpha 1,4 type of point?

linear straight line of glucose molecules for starch

alpha 1,6 type of point?

branch point for starch

Starch and glycogen have what points?

branch points and eventually linear string for new bond

Glycogen structure

alpha 1,4 linear and every so often alpha 1,6 : its structure itself is feathery.

Glycogen in which 2 body areas? What does one have that the other doesn't?

liver and muscle. Liver expresses glucose 6-phosphatase. Phosphate stuck on glucose n muscle doesn't have phoshphatase to remove it so metabolizes glucose. liver can remove phosphate and move it outside to maintain blood glucose levels.

Starch (2 types)

amylose linear (1,4) chain and amylopectin branched (1,6)

First enzyme that breaks down carb?

salivary amylase (enzyme to break down amylose is amylase)

Cellulose structure

beta 1,4 : linear string of glucose molecules. Amylase can't break down beta 1,4. Cellulose indigestible by human enzymes. Functions as a dietary fiber.

Sucrase, amylase, maltase, isomaltase vs lactose :

all break alpha 1,4 except lactose breaks beta 1,4

isomaltase: alpha 1,6

Dietary vs Function Fiber

nondigestable carb and lignin intrinsic/intact in plants

that intrinsic plant molecule - isolated, extracted or manfactured nondigestable carbs that have physiological beneficial effects on humans

Example: psyllium (Metamucil) for functional fiber (includes dietary component)

Fibers types w/ pectin example

Fibers property = diff functionalities. Groupable based on solubility, viscocity, and fermentability.

Pectins: stickly-like substances (high viscocity)

Solubility - soluble or come out of solution

Fermentability - can colon microbes metabolize it?

High vs low soluble, viscous, fermentability - for fibers

Some of our fibers low soluble, low viscous, low fermentability increase transit time through GI tract. They bulk up the stool. Ones in middle (medium, fermentability, medium viscosity) increase transit time n pull water in stool making it softer. Highly viscous, fermentable: increase nutrient bioavailability and will create short chain FA due to fermentability. Soluble, non-viscous - prebiotic/probiotic food like immulin, GOS

FIber Health Benefits

affect nutrient absorption, glycemic index (more fiber, lower glycemic index as it slows rate of digestion - good thing for Type II diabetes and makes them feel full longer - increasing satiety to consume less food) - soluble fibers

Cheerios - fibers

Good for health. Has fibers that bind cholesterol and help its excretion. It doesn't help ppl lower cholesterol. It does help excrete cholesterol but patients already making so much.

FODMAP diet

Not a thing as non-celiac gluten sensitivity. They are either celiac or not.

FODMAP responsible for non-geliac gluten sensitivity (fermentable oligo, di, monosaccharides, and polyols). Colon microbiome can ferment them.

Shorter sugars are monosaccharides. Most problematic disaccharide is lactose. (became of lactase resistance and lactose intolerance).

High consumption of FODMAP - GI distress.

FODMAPS

has to be short duration and under supervision of dietician (1-2 weeks n then add FODMAPS back in). Their in food, grains, candies (Sugar alcohols) etc. Low FODMAP diet to get improvement in symptoms.

Lipids

everything hydrophobic is a lipid. Lipids can be FA or steroids (cholesterol based). Break down FA into triglycerides (storage), phosphoglycerides (phosphate head group to 2 fatty acid tails), and sphingolipids. Sphingolipids have sphingosine backbone (not glycerol backbone). Sphingosine is serine-palmatine (serine + 2 fatty acids). Phosphohead group (phosphatidyl choline) = sphingomyelins. If you put sugars, you get glycolipids.

FA

FA can be short-chain FA. In general, short-chain FA are all saturated FA. Not enough carbons to have double bonds.

Fermentable Fiber Metabolism Creates Volatile Short Chain FA Absorbed by Humans

Short chain FA can be branched like methyl group popping off one of the carbons. Short chain FA 2-5 carbons in length and include acetic acid, propionic acid, butyric acid, and valeric acid. Short chain FA in fiber - bacteria metabolizing fibers into short chain FA and directly absorbed into the bloodstream to liver to tissues for systemic effect. Colon cells like butyrate. Bacteria making butyrate - short chain FA from fiber metabolism. Butyrate feeds your own colon epithelium cells.

Short & Medium Chain FA Absorbed Directly to Portal Blood

Short chain/medium FA --> bloodstream --> liver.

6-12 carbons in length: mostly saturated or monounsaturated.

Odd chains like 7 carbons/9 possible. We can have branch points of medium chain FA.

The reason we only list 2 carbons is cuz acetyl-coA is 2 carbons and how we metabolize break down FA is removing 2 carbons at a time: acetyl-coA.

Once we have odd chain FA, we remove 2 carbons until we left with 3 and then we have priopionic acid (proprionate) --> TCA cycle and acetyl-coA. Proprioniate - can't remove 2 carbons and leave 1 carbon so leave it and enters TCA cycle.

Long Chains

12 carbons to 20 carbons in length. Talking abt myristic, palmitic, stearic, arachidic acid. The very long chains greater than 22 carbons: behenic, lignoceric, certocic acid, arachidonic acid.

Arachidonic acid is an omega-6 fatty acid found in fish oil, which is rich in omega-3 fatty acids.

We can have unsaturated, polyunsaturated, monounsaturated FA. Branch points FA. odd carbon length fatty acids, and branched.

Naming Fatty Acids

Omega first double bond from methyl end

Delta describes each double bond from COOH end

Carbon # and number of double bonds: 18 : 3 which is 18 carbons and 3 double bonds

2 Essential FA Drive Long-Chain Polyunsaturated Acids

Alpha linolenic acid is omega-3 FA, 3 double bonds 18 carbons in length. Linoleic acid is essential n6, 2 double bonds, 18 carbons in length - body can't make more than 16 so need essential 18 carbons.

Share same desaturation/elongase enzymes to make things like EPA and DHA and arachidonic acid in our body. Same enzymes. Its only one enzyme desaturase on n-3 and n-6 FA.We have elongase enzyme to add 2 carbons as acetyl-coA to FA to make them longer.

If we consume more n-6 FA so all delta 6 desaturase enzyme taken up by metabolizing n-6 to arachidonic acid and don't have enough n-3 or delta-6-desaturase to make EPA and DHA. We should consume fish 2-3 times a week or take fish oil supplement and reduce n-6 consumption.

n3 LC-PUFA in Health & Disease

More about omega 3, 6 FA. Historically, we had a good ratio of N6: N3 with very little saturated fat. Total fat not bad but low compared to today. Started industrializing food supply, FA went up. Blip of trans fatty acids that came back down. N6/N3 starting 1900 and after and separate. Oils contain mainly n6. Fish oil dropped a little. Now the U.S. consumes 12 N6: 20 N6: 1 N3.

Drug of EPA and DHA. Specifically ethyl esters that add another group to them but its rly just fish oil. Prescribe drug to treat hypertriglyceridemia. Elevated blood triglycerides go down.

Trans Double Bonds are Rarely Found in 'Natural' Fatty Acids

Trans fats a trans double bond. Fatty acids in nature: usually have cis-double bonds. Trans double bonds from processing fat/fat foods. Hydrogenated fats to make liquid fats solid at room temp like margenine (hydrogenated so now solid at room temp), oil, and other fats. Hydrogenation can introduce trans double bonds in FA (not good for health). They lower HDL (good cholesterol) and raise LDL (bad cholesterol), increase TG/inflammation, and basically heart attack. Reason it's only blip on radar. Its required to be listed on food labels so ppl avoid it.

Fatty Acids are Metabolized for Energy OR Metabolized for Lipid Mediator Generation

FA are imp and ratio of N6: N3 imp cuz those get incorporated to FA of phospholipid membranes. Fat you eat/make incorporated to plasma membranes so if I only eat N6, I only have N6 in phospholipids and only metabolize arachidonic acid (only FA I have) to proinflammatory lipid mediators. Proinflammator prostaglandins, leukotrienes, and thromboxanes. Little DHA to metabolize to anti-inflammatory mediators. Not true only N3 is inflammatory & N6, proinflammatory - thats lose generalization that the public gets confused abt. N6's aren't all proinflammatory but mostly r. N'3 not always antiinflammatory but mostly are. Fish oil isn't good for everything.

Fatty Acid + Glycerol = Acylglycerol

Triglycerides - glyceride backbone with any fatty acid (saturated, unsaturated, branched stain, etc - doesn’t matter). Its the energy storage form of acetyl-coA. If we remove one FA, we have a free carbon sugar alcohol - glycerol. One carbon is open so we can add a phosphate head group to get phospholipid bilayer. FA any chain - any degree of unsaturation. Head group can be one of certain classes: phosphatidylcholine (lecithin), phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol (seen in signaling).

Phosphatidylserine in apoptosis. It coalesces to the inner leaflet of plasma membrane w/bilayer. Inner leaflet towards cytosol. Outer leaflet towards ECF. When the cell gets signal to die/apoptose, phosphatidylserine flips to outer leaflet ECF.

All phospholipids act as emulsifiers like micelles (making small lipid droplets cuz of phosphate head group n tails). Head towards outside and tails inside of sphere. Lecithin on food labels and helps with emulsification. Protein powders have soy lecithin to emulsify protein/fats. GI patients-lecithin.

Just know phosphatidylinositol (seen in signaling) - no details needed.

Ceramide

Fatty Acid (any chain length, any degree of unsaturation FA) + Sphingosine (Serine + Palmitate) = Ceramide. If we add another FA to the nitrogen of serine, we get ceramide. Notice free hydroxyl group on serine where phosphate head group or carbs can be added to OH group on serine.

Ceramide + Phospho-Head Group = Sphingolipids Ceramide + Sugar = Glycolipids

Sphingomyelin - myelination of neurons NOT TRUE. Its just a phospho sphingolipid that's in all plasma membranes. The glycolipids n cerebro lipids - enrichment in nervous tissue like galactic cerebro lipids (sphingolipids w/ galactose). The glycolipids further broken down to cerebrosides n gangliosides. Diff: cerebrosides only have sugar while gangliosides add sialic acid which is known as neuraminic acid or NANA. Cleaving neuraminic acid using neuraminidase.

Fatty Acid Melting Temp Important in Membrane Fluidity

Sections of every cell called lipid/cytoplasmic domains. There are domains of plasma membrane. Lipid rafts tend to be viscous, thick, sticky microdomains that proteins don't move easily through. Proteins floating around. To make membrane domain viscous, its enriched in cholesterol, sphingolipids, saturated FA, and long chain FA. Long chain saturated FA have a higher melting temp bc they r saturated/straight and pack them in nice/tight. Compared to unsat FA that have cis double bond. Creating loops or bends in FA. Now we can't pack as tightly so melting temp goes down n more liquid at room temp. To make membrane domain more thicker/viscous, pack with long chain/saturated FA.

Steroids r lipids and cholesterol based lipids. If we look at cholesterol ring structure multiple rings joined together. To make it cholesterol, we add OH groups (steroil = steroid + OH). We can make cholesterol in body is enough not needed from diet. We see steroid ring structure like bile acid like cholic acid. Even in some hormones like estradiol, testosterone, vitamin D.

Cholesterol precursor for steroid and bile acids (emulsifiers)

- Testosterone, estradiol, aldosterone, cortisol, all have cholesterol steroid ring structure and can be derived from cholesterol so all steroid hormones

Generic Steroid Hormone Mechanism of Action; Genomic & Non-Genomic Actions

Steroid hormone all function as steroid hormone transcription factors of ligands and other things. They have nongenomic functions but most function as transcription factors through changing expression of certain genes. Bc they r fat/lipid soluble, they need water/transport protein to keep it stable in a aqueous environment in blood. Once they get in cell, they can diffuse in lipid membrane cuz their soluble. Once in cell, another binding protein needed. Some are transcription factors like cortisol binding to cortisol receptor in the plasma membrane - homodimerizes to cortisol protein- complexes together- translocate to nucleus - bind to certain section of DNA - increase glucocorticoid response to genes.

Vitamin D circulates in the blood. Vitamin D to binding protein to cell that needs vitamin D - crosses plasma membrane - binds to vitamin D receptor - vitamin D binds to other proteins - forms a transcription complex - binds to DNA - recruits RNA pol/increase vit D response of genes.

Binding to specific DNA element - hormone response element (HRE) - if vitamin D response element (applies to A (retinoic acid response element)

Structure/Function of Fat-Soluble Vitamins (Vitamins A & D vs E & K)

Vitamin A, D both function like steroid hormone transcription factor ligand. Vitamin A has other function in the eye. Vitamin D does have cholesterol steroid ring structure. Doesn't come from cholesterol but comes from a cholesterol precursor. Just bc u make cholesterol, doesn't mean u make vitamin D. Rly u only need in summer like 15 min of hand/face exposure in sun for enough vitamin D. Other fat-soluble vitamins don't function as steroid function: only A/D have steroid hormone function. Only D has steroid ring structure. VItamin D & A function as steroid hormone transcription factor ligand.

non-cholesterol/steroid function, fat soluble:

Vitamin K (carboxylation) & Vitamin E (antioxidant)

What forms of vitamin A function in the eye? In other tissues?

Conjugating 2 glucuronic acid for excretion (Conjugation with glucuronic acid, a process known as glucuronidation, helps make vitamin A and its metabolites more water-soluble.). Vitamin A functions as a steroid transcriptional factor ligand (retinoic acid or trans-retinoic acid). Diff form with aldehyde and cis double bond that functions in the eye for vision.

Vitamin D Can Be Synthesized by Humans & Must be Activated to Function

Cholesterol precursor: 7-dehydrocholesterol can make vitamin D upon sun exposure in skin and deposits in skin. Once sunlight hits that, it makes vitamin D or cholecalciferol (D3- has to be hydroxylated before functional). 10-15 min of sun exposure (hand n face) gives most ppl enough vitamin D. Some pop it isn't enough - darker skin individuals need more time than some to make vitamin D. All dependent on angle of sun - where u live (latitude).

What is the likely cause of his bowed tibiae?

Likely had vitamin D deficiency at a young age. 2 of those genes that vitamin D will regulate is calbindin (D28/9K) genes Vitamin D - reg calcium homeostasis genes (one in intestine to absorb dietary calcium or kidney in kidney filter)

Calbindin - calciumbinding genes

Calbindin (intestinalal Ca absorption D9k)

Calbinding (renall Ca absorption) D28k